2010 AnnuAl REpoRT - Ciberdem

2010 Annual Report 

CIBERDEM 

Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas 

Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders


CIBERDEM 


Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders

Letter from the Scientific Director 

CIBERDEM began its activity over three years ago and it is now time to take stock of its achievements. Some are already 

evident and among these is the qualitative leap forward, to which the present report bears witness, as regards the number 

and excellence of publications. In line with international parameters, we consider it one of our main objectives to achieve 

the maximum number of publications in the first decile in each speciality and, in fact, as the present report shows, most of 

the groups have managed to publish several works at this level of competence. To this success we should add others, well 

documented in the report, such as the ability of groups to work together, especially in the case of clinical and basic research 

groups, which is a clear indication of our strong commitment to translational research, as well as an obvious demonstration 

that these associations between groups are advantageous when it comes to obtaining funding, both private and public, 

especially from the European Union. All this will soon allow us to put CIBERDEM firmly on the map of competitive biomedical 

research in Europe, particularly in the field of diabetes and associated illnesses. 

There is still a lot to do; in particular, we need to carry out further solid research which will have a significant impact on the 

prevention, diagnosis and treatment of diabetes and its complications. Such an ambitious objective requires time, but in my 

opinion, we are on the right track. The researchers have shown a remarkable capacity to obtain funding in order to promote 

collaborative structures as well as to develop competitive projects, it might be a risky business, but even so the objective is 

achievable. The report mirrors the reality of research in our country, but also shows us the way forward and the objectives 

we need to achieve. The criticisms received by the External Scientific Committee, as well as the considerations of the 

researchers themselves, have been an incentive to improve, but we also hope to receive positive interaction from the readers 

of this report. CIBERDEM’s groups want to collaborate, participate and generate biomedical science to benefit the patients 

suffering from diabetes, and in this sense are open to collaboration with others to make possible not just sound scientific 

articles, but also scientific discoveries which are applicable to the medicine of the future. The challenges are there, and so 

is the answer. 

Ramon Gomis 

CIBERDEM Scientific Director

Management report 

In its third year of existence, CIBERDEM has consolidated its achievements and has managed to attain all the objectives 

in its annual action plan. In particular, it has succeeded in reaching all the goals in its first strategic objective in connection 

with the encouragement of competitive translational research. It has also managed to greatly improve its record as regards 

participation in and leadership of European projects; it has fostered the development of and access to competitive platforms 

and has improved its training programme. Worthy of special note is the fact that it has succeeded in carrying out the first 

study of the prevalence of diabetes mellitus in Spain, which will have a great impact on the national health system. 

CIBERDEM has managed to take in its stride the budget cuts brought about by the global economic crisis. With considerably 

less funding available than in previous years, CIBERDEM has been obliged to redirect its scientific and human-resources 

strategies. Although there have been reductions in staff numbers and cuts in certain strategic plans of action, scientific 

production has risen and levels of synergy between CIBERDEM groups and international collaboration have been consolidated. 

Our challenges for the future include guaranteeing economic solvency so that our groups can continue to carry out research 

of excellence, foster cooperation with companies, and secure competitive funding. 

Ana Bosch 

CIBERDEM Managing Director

Contents 

Prologue 

Research results ..................................................................................7 

Project management ...............................................................................9 

Training programme ..............................................................................11 

Outreach activities ................................................................................13 

More about CIBERDEM ............................................................................15 

Research 

Transversal projects: Di@bet.es Study and CIBERDEM Projects ............................................20 

Technological platforms: Biobank and Metabolomics Platform .............................................26 

Area 1: Insulin signalling and resistance. Role in the onset of diabetes ......................................32 

Area 2: Dyslipidaemia, metabolic syndrome and microvascular complications of diabetes .......................52 

Area 3: Islet dysfunction, destruction and regeneration. Autoimmunity. Impact on the pathogenesis of diabetes ......90 

Epilogue 

Principal Investigator index ........................................................................131 

Keyword index ..................................................................................132 

Publications index ...............................................................................133

Prologue

Research results 

Publications 

In 2010, CIBERDEM published a total of 117 scientific 

papers in journals ranking in the first and second quartile 

of their speciality. The total number of articles published 

was higher than this, but here we refer only to those of the 

first and second quartiles. 

Of these 117 papers, 80% (93) were published in journals 

in the first quartile of their speciality and of these 40% (46) 

appeared in journals in the first decile. 

The total impact factor was 710.901 (source: ISI Web of 

Knowledge), which yields an average impact factor of 

6.076. If we take as an indicator the field of endocrinology 

and metabolism in the ISI Web of Knowledge, the first 

decile corresponds to 6.209 points, which attests to the 

degree of scientific excellence attained by CIBERDEM in 

the year 2010. 

In comparison with previous years, CIBERDEM not only 

consolidated its scientific results, it also increased them 

and improved them in terms of excellence and quality, both 

globally and in each separate scientific area. 

Also worthy of note is the increase in the number of scientific 

collaborations generated by CIBERDEM: 2010 saw a total of 

20 articles published in collaboration with other researchers, 

an increase of 50% on the figure for 2009. 

CIBERDEM also consolidated its collaboration with other 

CIBERs, the most tangible result being the publication of 

indexed articles, 26 of them with other CIBERs (CIBEROBN, 

CIBERER, CIBEREHD, CIBERSAM, CIBERESP). 

800 

600 

400 

200 

0 

Evolution of CIBERDEM’s Publications 

(2008-2010) 

2008 2009 2010 

Projects 

As a consortium, in 2010, CIBERDEM presented 4 

applications for funding in response to public calls in Spain, 

and 10 in response to European calls. Here are the details 

of the successful applications, which will be implemented 

in 2011: 

European calls 

DIATRAIN. DIAbetes Trans-national Research Advancement 

for INvestigators 

People Programme, 7th Framework Programme, Marie 

Curie Actions-COFUND Call, European Union 

Coordinator: CIBERDEM 

Budget: 443,037.99 € 

Duration: 4 years 

Current status (June 2011): Granted 

MEDIGENE. Genetic and environmental factors of insulin 

resistance syndrome and its long-term complications in 

immigrant Mediterranean populations 

Health Programme, 7th Framework Programme, European 

Union 

Partner (Deputy Coordinator): CIBERDEM 

Tentative budget: 321,381 € 


Current status (July 2011): In negotiation 

National calls 

Papel de las Fosfatifato Fosfatasas (PAP, Lipin) en la 

regulación de funciones celulares por medio del control de 

la biosíntesis de fosfolípidos y su relación con la obesidad 

Subprogramme for health research projects -Strategic 

Action in Health- (ISCIII-MICINN) 

Principal Investigator: Mercedes Miranda 

Budget: 137,000 € 


Reference: PI10-00967 

Current status (October 2010): Granted 

Articles 

Impact Factor 

20 

15 

10 

5 

0 

2008 2009 2010 

Impact Factor Average IntraCIBER Publications 

The graphs clearly show the increase in CIBERDEM’s scientific productivity. 

While the number of articles published increased slightly, 

their quality and scientific impact did so significantly in 2010, which 

confirms CIBERDEM’s trend towards excellence and prominence 

on the international scene. 2010 also saw a definite increase in the 

number of articles published as the result of collaboration between 

different CIBERDEM research groups, this thanks to the synergies 

built up over the years of the consortium’s existence. 


7

Funcionalidad de HDL en la diabetes mellitus y la 

hiperhomocisteinemia: estudios en pacientes y en modelos 

animales 

Subprogramme for health research projects -Strategic 

Action in Health- (ISCIII-MICINN) 

Principal Investigator: Josep Julve 

Budget: 110,546.80 € 


Reference: PI10-0277 

Current status (October 2010): Granted 

Patents and other Transfer of Knowledge 

In 2010, CIBERDEM groups generated 5 patents, 3 clinical 

practice guidelines and 1 spin-off: 

Patents 

European patent: Gene therapy composition for use in 

diabetes treatment 

Patent application number: EP10169309.1 

Priority country: Europe 

Priority date: July 12, 2010 

Inventors: F Bosch, E Ayuso, D Callejas 

Universitat Autònoma de Barcelona 

European patent: Telomerase reverse transcriptase for 

protection against ageing 




Inventors: MA Blasco, B Bernardes, F Bosch, E Ayuso 

Universitat Autònoma de Barcelona and Centro Nacional 

de Investigaciones Oncológicas 

International patent: Composition comprising an androgen 

receptor blocker and an insulin sensitizing agent and use 

thereof for treatment of polycystic ovary syndrome 

Patent application number: PCT/BE 02/00052 

Inventors: F de Zegher, L Ibáñez 

University of Leuven and University of Barcelona (2010) 

Clinical practice guidelines 

Insulin resistance in children: consensus, perspective, and 

future directions 

Journal of Clinical Endocrinology & Metabolism, 95, 5189- 

5198 (2010) 

Institution: Consensus Meeting (ESPE-LWPES- 

ISPADAPPES-APEG-SLEP-JSPE) 

Authors: C Levy-Marchal, S Arslanian, W Cutfield, A Sinaiko, 

C Druet, ML Marcovecchio, F Chiarelli; ESPE-LWPES- 

ISPADAPPES-APEG-SLEP-JSPE; Insulin Resistance in 

Children Consensus Conference Group 

Assessment of cardiovascular risk and prevention of 

cardiovascular disease in women with the polycystic ovary 

syndrome: a position statement by the Androgen Excess & 

Polycystic Ovary Syndrome (AE-PCOS) Society 



Institution: Androgen Excess & Polycystic Ovary Syndrome 

(AE-PCOS) Society 

Authors: RA Wild, E Carmina, E Diamanti-Kandarakis, A 

Dokras, HF Escobar Morreale, W Futterweit, R Lobo, RJ 

Norman, E Talbott, DA Dumesic 

Alimentación para Personas Mayores (2010) 

Institution: Instituto Danone 

Authors: M Serrano Ríos, P López Nomdebeu, JM Ribera 

Casado, A Sastre Gallego 

Spin-off 

Beyond Food SL 

Description: Support to industry for the validation of 

functional food 

Researchers: L Masana, R Solà, JC Vallvé, J Ribalta, J 

Girona, C Prats 

Collaborating institution: Universitat Rovira i Virgili 

Year of creation: 2007 

National patent: Uso de la proinsulina para la elaboración de 

una composición farmacéutica neuroprotectora, composición 

terapéutica que la contiene y sus aplicaciones 

Patent application number: ES2331342B1 

Inventors: EJ de la Rosa Cano, F de Pablo Dávila, P Boya 

Tremoleda, S Corrochano Sánchez, P de la Villa Polo, R 

Barhoum Tannous and F Bosch Tubert 

CIB-CSIC, Universitat Autònoma de Barcelona and 

Universidad de Alcalá de Henares (2010) 

National patent: A method for the in vitro proliferation of 

cells coming from tissues of endodermic origin 

Patent application number: P201030365 

Inventors: A Khoo, F Martín, B Soria 

FPS-UPO (2010) 

8 CibeRdem

Project management 

Introduction 

The Spanish Biomedical Research Centre in Diabetes 

and Associated Metabolic Disorders (CIBERDEM) 

works hard to obtain additional competitive funding to 

develop research into diabetes and associated metabolic 

disorders. 

Currently, CIBERDEM’s project management department is 

involved in all project phases, giving support to CIBERDEM 

researchers in the preparation and presentation of 

proposals, and also the submission, implementation and 

justification of funded projects. 

CIBERDEM aims to expand its presence in the worldwide 

scientific community in its specific research field. The 

strengthening of national, international and intersectorial 

collaboration in research will help us to obtain more and 

better scientific outcomes with high translational impact. 

Objectives 

To achieve excellence, to obtain competitive funding and to 

monitor projects from implementation to justification. 

To give support in the preparation of proposals by 

researchers in the consortium. 

To internationalize Spanish biomedical research, in 

particular as regards CIBERDEM’s main lines of research 

into diabetes and associated metabolic disorders. 

To encourage and motivate researchers to participate in 

calls and seize opportunities to take part in different kinds 

of programmes through the monthly internal newsletter. 

Coordination 

Gemma Pascual, CIBERDEM Project Manager, and Donald 

Mc Donagh, CIBERDEM Proposal Writer. 

Achievements in 2010 

CIBERDEM’s own actions 

These are transversal initiatives implemented by members 

of the consortium and in some cases with the collaboration 

of external personnel. These translational projects try to 

answer complex questions which could not be resolved 

by one group working alone and will prove of benefit to 

diabetic patients and the healthcare system in general. 

In 2010, 15 research actions were underway, although 

they had been implemented in previous years. These 

were: 1) the Di@bet.es Study, which is the first national 

epidemiological study that will provide the Spanish health 

authorities with real figures relating to the prevalence of 

type 2 diabetes (diagnosed as such or not) in addition to 

other relevant parameters; for more information see page 

21. 2) 14 CIBERDEM projects defined as translational 

initiatives resulting from internal collaborative work: 

-IREVAS, NEURONET-DIAB, INGENFRED, MODIAB, DOTUM, 

DIASOBS, GIDIPRED, CHILDBODYFAT, ANTIBECELL, 

LOWHDL, METADIAB, ENDODIAB, IODURE and STEMOB; 

for more information see page 23. 

CIBERDEM transversal initiatives are 

possible because of the synergistic work 

of nearly all the centre’s research teams, 

with both basic and clinical profiles 

National and Autonomous Community grants obtained 

During 2010, two proposals submitted under the Strategic 

Health Action Call of the National Scientific Research, 

Development and Technological Innovation Plan of the 

Spanish Ministry of Science and Innovation received 

grants. One was directed by Dr Mercedes Miranda 

(Phosphatidate phosphatases (PAP, Lipin) regulation of 

cellular functions by controlling phospholipid biosynthesis 

and its relation with obesity) and the other by Dr Josep 

Julve (HDL functionality in diabetes mellitus and 

hyperhomocysteinaemia: studies in patients and animal 

models); both are members of CIBERDEM’s postdoctoral 

staff. Dr Mercedes Miranda, whose centre is located in 

Tarragona, was also awarded an Autonomous Community 

mobility grant by AGAUR. 

International grants obtained 

Turning to international grants, in 2010, an institutional 

proposal was submitted to the Marie Curie-COFUND 

Call in the People Programme as part of the European 

Commission’s 7th Framework Programme (FP7). This 

proposal, DIATRAIN (DIAbetes Trans-national Research 

Advancement for INvestigators), involved two post-doctoral 

mobility schemes and was led by Dr Ramon Gomis. The 

centre was invited to negotiate; in 2011 this process should 

be concluded and it is expected that implementation of the 

project will begin. 

CIBERDEM also submitted two initiatives as coordinator 

and two initiatives as a partner in response to the 

FP7 Health Call under the Cooperation Programme 

of the European Commission. Of these, one, entitled 

“Genetic and environmental factors of insulin resistance 

syndrome and its long-term complications in immigrant 

Mediterranean populations - MEDIGENE”, is currently 

under negotiation and is expected to be approved before 

the year is out. 


9

A) 

NRP 21% 

Autonomous Community 

calls 7% 

NRP - Strategic Health 

Action Call 14% 

Private funds 58% 

B) 

Other public institutions 13% 

Private funds 25% 

European Commission calls 62% 

A) National and Autonomous Community grants. Applications 

made for funds at a national level were divided as follows: private 

institutions (58%), National Scientific Research, Development and 

Technological Innovation Plan (NRP) (21%), and Strategic Health 

Action Call as a specific programme under the NRP (14%). Autonomous 

Community grants are also shown (7%). 

B) International grants. The graph shows the proportion of applications 

for funding submitted internationally: European Commission 

(62%), other public institutions (13%), and private funds (25%). 

Future challenges 

The Project Management Department wishes to increase 

its participation in the Autonomous Community, national 

and international environments in order to obtain additional 

funding to enrich the scientific outcomes of the consortium. 

Our principal goal is to increase the rate of success of our 

proposals in competitive calls. 

New ways forward are foreseen, mainly through the private 

sector, in the form of both collaboration and requests 

for additional funding, as the report of the Road Map 

for Diabetes Research in Europe - DIAMAP (European 

Commission - FP7) suggests. 

Come what may, the prevention, treatment and cure of 

diabetes and its associated metabolic disorders will 

continue to be the main focus of all research carried out 

under the aegis of CIBERDEM. 

10 CibeRdem

Training programme 

Introduction 

The training of research staff was envisaged right from 

the start of CIBERDEM and has been at the very centre 

of strategic action plan design ever since, especially the 

training of predoctoral staff and specialists with tenure. 

With the idea of developing a training plan, overseeing its 

work and guaranteeing its smooth running, CIBERDEM 

appointed a training committee made up of: President 

Antonio Zorzano and Committee members Ramon Gomis, 

Angel Nadal and Joan J Vendrell. 

The aim of the teaching programme is to encourage the 

acquisition and transfer of knowledge, both basic and 

clinical, among the research staff under training in the 

groups which make up CIBERDEM in order to achieve the 

general research objectives as defined while making better 

use of the resources available. The teaching programme 

represents an investment in our younger staff and in the 

future of the consortium itself. 

Objectives 

Our objectives are to create and implement a research 

staff training programme aimed especially at predoctoral 

researchers which will help participants to consolidate 

their investigative career, improve their future prospects 

and bring added value to the groups to which they belong; 

to enhance the methodological, technical, communicative 

and organizational skills of the younger members of the 

research staff and improve their scientific capacity in 

general; and to increase mobility, communication and the 

transfer of scientific knowledge between the groups which 

make up CIBERDEM in order to develop their scientific 

proficiency, both basic and clinical. 


Renewal of contracts for predoctoral research staff 

Objective: A commitment to support young researchers so 

that they can carry out their work in the field of diabetes 

in a group of excellence linked to CIBERDEM. In 2010 

CIBERDEM renewed the contracts of predoctoral grant 

holders as shown below: 

Name 

M Carrasco 

E Rubio 

L Cadavez 

V Moreno 

Activity 

The role of the blockage of type 1 VEGF receptor 

(VEGFR1) in obtaining insulin from adult pancreatic 

stem cells 

The role of adipose tissue and adipokines in the 

development of type 2 diabetes 

The role of BACE in the functioning of pancreatic islets 

The role of IRS-2 in the regeneration of the endocrine 

pancreas 

The organization of an annual training course in 

translational matters with special emphasis on clinical 

research, aimed at CIBERDEM’s predoctoral researchers 

(contracted or attached) 

Objective: Regular ongoing training for predoctoral 

researchers (under contract or attached) covering subjects 

of translational interest given by experienced CIBERDEM 

specialists or outside speakers. 

CIBERDEM organized the following training course: 

Title Physiological Techniques Applied to Islets of Langerhans 

Date 20-21 January, 2011 

Venue Elx (Alicante) 

Hours of classes 9 hours of classes divided between 

theoretical and practical sessions: 

a. Theory: 5 sessions of 1 hour each 

b. Practicals: 3 hours 

Participants 25 CIBERDEM junior researchers 

Clinical Symposium on Diabetes and Associated 

Metabolic Diseases 

The first Clinical Symposium organized jointly with the MSD 

pharmaceutical company, which sponsored the event. 

Aimed exclusively at professional clinicians. 

Objective: To create an environment for the dissemination 

and exchange of research results. Papers were given by 

international speakers and members of CIBERDEM. 

Date 26-27 November, 2010 

Venue Barcelona 

Hours of classes 7 hours divided into 4 sessions 

Participants 127 attendees, including 32 CIBERDEM 

researchers 

EASD/JDRF Joint Strategic Meeting: Type 1 Diabetes 

With the participation of the European Association for the 

Study of Diabetes (Europe) and the Juvenile Diabetes 

Research Foundation (USA). 

Objective: A multi-disciplinary symposium whose aim was to 

design future strategies for diabetes research, with special 

emphasis on clinical and basic translational research with 

real potential; to encourage cutting-edge research in an 

international context and establish external collaboration in 

CIBERDEM’s main fields of research; and to facilitate access 

to high-level training in the sphere of diabetes research. 

Date 18-19 November, 2010 

Venue Barcelona 

Hours of classes 18 hours of classes, divided into 4 

sessions 

Participants 100 postdoctoral students, including 12 from 

CIBERDEM 


11

Training periods 

Objective: For junior and senior researchers to spend short 

periods (a maximum of three months) in other laboratories 

to broaden their scientific knowledge in specific techniques, 

collaborate with other groups and develop joint experiments. 

In 2010, 8 training periods of this type were made possible 

thanks to CIBERDEM. 

Theses defended and directed by researchers attached to 

CIBERDEM 

In 2010, a total of 21 doctoral theses were read. 

12 CibeRdem

Outreach activities 

CIBERDEM Fundraising 

In its effort to continue supporting the work of its research 

groups, CIBERDEM has designed a strategic fundraising 

plan with two clearly defined lines of action: on the one 

hand, actions aimed at private individuals, and on the 

other, those aimed at the business community. In 2010, 

implementation of the private individual plan was begun 

and work started on drafting the business community plan. 

The objective of this initiative is to increase the level of 

awareness of the problem of diabetes in Spain in order to 

produce the active participation of key sectors in Spanish 

society and thus generate funds to carry out research 

projects to help to prevent, treat and cure diabetes. 

In order to attain its objectives, CIBERDEM introduced its 

Investiga la diabetes (research diabetes) initiative, a nonprofit-making 

venture which seeks to involve all patients, 

their families and society at large in the fight against 

diabetes through research. 

In 2010, CIBERDEM began the initiative in several of 

Spain’s Autonomous Communities (Andalusia, Catalonia, 

Castile–La Mancha, Castile and Leon, Madrid, Valencia, 

the Balearic Islands, the Canary Islands and the Basque 

Country) involving a total of over 3,000 people. The Investiga 

la diabetes bracelet was also launched, the idea being to 

make people aware of the fight against this disease and to 

secure their involvement. 

We should also like to take this opportunity to thank all the 

patients’ associations which have collaborated with us for 

their support and commitment. We should also like to thank 

all CIBERDEM researchers for their contribution to helping 

to popularize this initiative at events both at a national level 

and within the Consortium: the Public Awareness Event and 

the Annual Meeting. 

3rd Public Awareness Event 

The 3rd CIBERDEM Public Awareness Event «Investiga la 

diabetes’10» was held at the Casa de la Ciencia (CSIC) in 

Sevilla, on November 13, 2010. The programme included 

exhibitions and interactive activities with the aim of 

showing the general public the latest advances in diabetes 

research. More than 300 people attended the event and 

took part in the different activities, including the lecture 

given by Dr Bernat Soria, researcher and ex-health minister, 

on the research being done in diabetes. Also, researchers 

and members of CIBERDEM participated in the creation 

and development of scientific workshops which opened up 

the world of science to all who attended. This event also 

motivated people to take part and give their support to 

diabetes research. 

Dr Franz Martín, Dr Ramon Gomis, Dr Anna Novials and Dr Bernat 

Soria, in Sevilla, on November 13, 2010. 

Leave your mark! 

www.investigaladiabetes.org 


13

3rd Annual Meeting 

More than 140 CIBERDEM researchers and staff members 

met to attend the 3rd CIBERDEM Annual Meeting, held 

in Prullans (Cerdanya, Lleida, Spain) on October 25, 26 

and 27, 2010. This scientific meeting allowed CIBERDEM 

research groups to share information on methods and the 

results of research projects with one another by means 

of 64 posters and 32 oral communications divided into 7 

different sessions. One noteworthy feature was that three 

sessions were organized to discuss CIBERDEM Scientific 

platforms, European Initiatives and a Conference on the 

Study Di@bet.es. 

The meeting was received with great enthusiasm and 

members were able to interact with one another and 

prepare the way for future collaborations. 

www.annualmeeting.ciberdem.org 

Cover of the 3rd Annual Meeting Abstract Book. 

Poster of the 3rd Public Awareness Event. 

14 CibeRdem

More about CIBERDEM 

The Centro de Investigación Biomédica en Red de Diabetes 

y Enfermedades Metabólicas Asociadas (CIBERDEM) 

is a public research consortium which was founded on 

December 3rd 2007 and is financed by the Instituto de 

Salud Carlos III (ISCIII) and the Ministerio de Ciencia e 

Innovación (MICINN). 

CIBERDEM is made up of 32 research groups based in 

different hospitals, universities and research centres 

throughout Spain. The main aim of CIBERDEM is to 

promote research into diabetes and associated metabolic 

disorders, identifying the genes which predispose to these 

diseases and the environmental factors which contribute to 

their development; to discover the molecular mechanisms 

involved in the alteration of insulin secretion and signalling; to 

determine the molecular and cellular mechanisms involved 

in the formation and destruction of pancreatic beta cells; 

to study strategies for substitution of this cell mass; and 

to investigate the signals which link obesity and diabetes. 

Of special interest is research into the complications of 

diabetes and associated metabolic disorders. 

CIBERDEM is divided into three research areas: 

Area 1. Insulin signalling and resistance. Role in the onset 

of diabetes 

Area 2. Dyslipidaemia, metabolic syndrome and 

microvascular complications of diabetes 

Area 3. Islet dysfunction, destruction and regeneration. 

Autoimmunity. Impact on the pathogenesis of diabetes 

Research Areas 

Area 1 

Area 2 

Area 3 

Steering Committee 

Technological Platforms 

Biobank 

Metabolomics Platform 

CIBERDEM’s organization chart. 

Management Committee 

Permanent Commission 

Scientific Director 

Adjunct Scientific Director 

External Scientific Committee 

Managing Director 

Management Office 

The nature, goals and financing of CIBERDEM are 

enshrined in its statutes, published in the Boletín Oficial 

del Estado (BOE) number 49, of February 26th, 2008. The 

approval of CIBERDEM’s new statutes on May 14th 2010 

brings, amongst other things, a change in the organization 

of its scientific activity: where before there were scientific 

areas, there are now programmes. These changes will 

become apparent in 2011. The main governing bodies of 

CIBERDEM are as follows: 

Management Committee 

This is made up of three representatives of the Instituto de 

Salud Carlos III and one representative from each of the other 

bodies in the consortium; it is the supreme governing body of 

CIBERDEM and exercises general control over the organization. 

President 

José J. Navas, Director of the Instituto de Salud Carlos III 

(ISCIII) 

Members 

Pascual Sanz, Consejo Superior de Investigaciones 

Científicas (CSIC) 

Rubén Moreno, Fundación Centro de Investigación Príncipe 

Felipe 

Juan Viña, Fundación Hospital Clínico Universitario de 

Valencia 

Emilià Pola, Fundación IDIBELL 

Francesc Vidal, Fundació Institut d’Investigació Sanitària 

Pere Virgili 

José Luis de Sancho, Fundació Institut de Recerca Hospital 

Universitari Vall d’Hebron 

José Francisco Cañón, Fundación Instituto Mediterráneo 

para el Avance de la Biotecnología Sanitaria 

Emili Bargalló, Fundación para la Investigación y Docencia 

Sant Joan de Déu 

Juan Antonio Álvaro, Fundación Jiménez Díaz 

Margarida Corominas, Fundació Privada Institut de Recerca 

Biomèdica 

Carmen Garaizar, Fundación Vasca de Innovación e 

Investigación Sanitarias 

Jaume Kulisevsky, Institut de Recerca Hospital de la Santa 

Creu i Sant Pau 

Pastora Martínez, Institut d’Investigacions Biomèdiques 

August Pi i Sunyer (IDIBAPS) 

Elena Andradas, Servicio Madrileño de Salud 

Ana Ripoll, Universitat Autònoma de Barcelona 

Xavier Meneses, Universitat de Barcelona 

Carmen Acebal, Universidad Complutense de Madrid 

Salvador Viniegra, Universidad Miguel Hernández 


15

José Manuel Rosado, Universidad Pablo de Olavide 

Secretary 

Ana Bosch, CIBERDEM Managing Director 

Permanent Commission 

This consists of the President of the Management Committee, 

the Scientific Director of the consortium and four members 

representing the other participating institutions. It evaluates 

the budgets, annual accounts and all reports to be submitted 

to the Management Committee for approval. 

President 

Joaquín Arenas, Subdirector General de Redes (ISCIII) 

Members 

Emilià Pola, Fundación IDIBELL 

Margarida Corominas, Fundació Privada Institut de Recerca 

Biomèdica 

José Manuel Rosado, Universidad Pablo de Olavide 

Carmen Ayuso, Fundación Jiménez Díaz 

Secretary 

Ana Bosch, CIBERDEM Managing Director 


This is made up of the Scientific Director, the Coordinator 

of each research area and the Training Director. It is 

responsible for the scientific activity of CIBERDEM and 

establishes its plans of action. 

Ramon Gomis, Scientific Director and President of the 


Anna Novials, Adjunct Scientific Director 

Manuel Benito, Coordinator of Area 1 

Rafael Carmena, Coordinator of Area 2 

Fàtima Bosch, Coordinator of Area 3 

Antonio Zorzano, Training Director 

Ana Bosch, Managing Director and Secretary of the 


External Scientific Committee 

This is made up of important figures whose professional or 

scientific contributions to the field of health sciences are in 

tune with the aims and objectives of CIBERDEM. It is the 

consortium’s scientific advisory body and it evaluates each 

year’s activity as well as that of all the research groups. 

Research Groups 

Madrid PIs Carmen Álvarez (Univ. Complutense), Manuel 

Benito (Univ. Complutense), Enrique Blázquez (Univ. 

Complutense), Héctor F Escobar Morreale (Hospital 

Ramón y Cajal), Flora de Pablo (CSIC Research Centre), 

Sonia Fernández Veledo (Univ. Complutense), Manuel 

Serrano Ríos (Hospital Clínico), Mario Vallejo (CSIC 

Research Centre), María Luisa Villanueva Peñacarrillo 

(Fundación Jiménez Díaz), Ángela Martínez Valverde (Univ. 

Complutense) 

Valladolid PI Jesús Balsinde (CSIC Research Centre) 

Vizcaya PI Luis Castaño (Hospital de Cruces) 

Barcelona PIs Francisco Blanco Vaca (Hospital Sant 

Pau), Fàtima Bosch (CBATEG Research Centre), Anna 

Novials (IDIBAPS Research Centre), Jorge Ferrer (IDIBAPS 

Research Centre), Ramon Gomis (IDIBAPS Research 

Centre), Manuel Vázquez Carrera (Univ. Barcelona), 

Anna M Gómez Foix (Univ. Barcelona), Joan J Guinovart 

(IRB Research Centre), Antonio Zorzano (IRB Research 

Centre), Eduard Montanya (Hospital Bellvitge), Rafael Simó 

(Hospital Vall d’Hebron), Lourdes Ibáñez (Hospital Sant 

Joan de Déu) 

Tarragona PIs Xavier Correig (Metabolomics Platform), 

Joan J Vendrell (Hospital Joan XXIII), Lluís Masana (Hospital 

Sant Joan Reus) 

Valencia PIs Rafael Carmena (Hospital Clínico), Deborah 

Burks (Príncipe Felipe Research Centre) 

Alicante PI Angel Nadal (Univ. Miguel Hernández) 

Málaga PI Federico Soriguer (Hospital Carlos Haya) 

Sevilla PI Franz Martín (CABIMER Research Centre) 

Valladolid 

Vizcaya 

President 

José M Ordovas, Human Nutrition Research Center, Boston (USA) 

Members 

Decio Eizirik, Gene Expression Unit - Diabetes Research 

Center VUB, Brussels (Belgium) 

Ele Ferrannini, Institute of Clinical Physiology, Pisa (Italy) 

Francesc Xavier Pi-Sunyer, Division of Endocrinology, Diabetes 

and Nutrition, St Luke’s-Roosevelt Hospital, New York (USA) 

Antonio Vidal-Puig, University of Cambridge - Addenbrooke’s 

Hospital, Cambridge (UK) 

Madrid 

Sevilla 

Málaga 

Barcelona 

Tarragona 

Valencia 

Alicante 

16 CibeRdem

Human Resources 

In 2010, CIBERDEM had a total of 437 researchers; of 

which 124 belonged to CIBERDEM’s own staff (including 

the Management and Coordination Office) and 313 were 

attached staff. The following two graphs show a breakdown of 

CIBERDEM’s own staff by category, type of contract and sex: 

40 

39 

35 

30 

Permanent 

Temporary 

25 

20 

20 

15 

14 

10 

9 

8 8 

7 

6 

6 

5 

3 

2 

1 

1 

0 0 0 

00 

0 

Doctorate Doctorate Bachelor's degree Bachelor's 

(4 year) degree Bachelor's (3 year) Technician Technician Management Management staff Management (level 1) Management 

staff (level 2) Management 

staff (level 3) Management 

staff (level PhD 4) student PhD student 

degree (4 year) degree (3 year) 

staff (level 1) staff (level 2) staff (level 3) staff (level 4) 

35 

35 

30 

25 

24 

Men 

Women 

20 

18 

15 

10 

10 

10 

5 

0 

6 

5 

4 4 

3 

2 

1 1 1 

0 0 0 0 

Doctorate 

Bachelor's 

Bachelor's 

Technician 

Management 

Management 

Management 

Management 

PhD student 

degree (4 year) 

degree (3 year) 

staff (level 1) 




Financial Highlights 

In 2010 CIBERDEM expended a total of 5,852,507.79 €, 

broken down as follows: 

Scientific Areas 3,324,304.40 € 

Biobank 254,264.83 € 

Metabolomics Platform 77,381.66 € 

Di@bet.es Study 351,829.70 € 

Transversal Projects 881,741.93 € 

Training Programme 86,624.83 € 

Management/Coordination 876,360.44 € 

Scientific Areas 

Biobank 


Di@bet.es Study 

Transversal Projects 

Training Programme 

Management/Coordination 

58% 

6% 

1% 

4% 

15% 

15% 

1% 


17

Research

Transversal projects 

Di@bet.es Study and CIBERDEM Projects 

Technological platforms 

Biobank and Metabolomics Platform 

Area 1 

Insulin signalling and resistance. Role in the onset of diabetes 

Area 2 

Dyslipidaemia, metabolic syndrome and microvascular complications of diabetes 

Area 3 

Islet dysfunction, destruction and regeneration. Autoimmunity. Impact on the pathogenesis of diabetes 


19

Transversal projects 


CIBERDEM Projects


Introduction 

Attempts to halt the growing presence of diabetes in 

Spanish society, a cause of concern for both public and 

private healthcare systems, require reliable and accurate 

data on the incidence of diabetes in different groups within 

the Spanish population. Di@bet.es, a joint initiative of the 

Spanish Diabetes Federation (FED), the Spanish Diabetes 

Society (SED) and CIBERDEM, was born with the goal of 

providing improved knowledge of the epidemiology of 

diabetes in Spain. 

CIBERDEM, primary funding organization of Di@bet.es, 

believes firmly in the importance of the epidemiological 

information that the study will provide as a point of reference 

for measuring the success of its programmes. The results 

of this study will assist CIBERDEM groups in focusing their 

research on relevant pursuits and will allow public and 

private institutions to formulate more efficient and effective 

strategies for diabetes prevention, diagnosis, treatment and 

research. 

Objectives 

To determine the overall incidence (known and unknown) of 

type 2 diabetes mellitus in a representative sample of the 

Spanish population. 

To determine the relationship between the incidence of 

type 2 diabetes mellitus and the nutritional habits and 

physical activity of the individuals within the sample, as 

well as relevant information regarding their demographic 

and genetic characteristics. 

To provide a scientific tool for assessing institutional health 

strategies. 

To determine the incidence of impaired fasting glucose and 

impaired glucose tolerance, insulin-resistance, hypertension, 

dyslipidaemia, obesity, and metabolic syndrome in a 

representative sample of the Spanish population. 

To determine the relationship between the incidence of 

these disorders and the nutritional habits and physical 

activity of the individuals within the sample. 

To provide a collection of human serum samples for 

carrying out studies on the analysis of gene-environment 

interaction in the pathogenesis of diabetes. 


Direction Federico Soriguer (Hospital Carlos Haya-IMABIS, 

Málaga, and CIBERDEM) 

Coordination Gemma Pascual (CIBERDEM Management 

Office) and Gemma Rojo (Hospital Carlos Haya- IMABIS, 

Málaga, and CIBERDEM) 

Field work regions. 

Central region 

Northern region 

Southern region 

Northeastern region 

Eastern region 

Northern region Field work coordination and CIBERDEM 

Management: Luis Castaño (Hospital de Cruces, Bilbao, 

and CIBERDEM) Field work: Alicia Cobo, Ana María Megido 

Northeastern region Field work coordination: Albert Goday 

(Hospital del Mar de Barcelona) CIBERDEM Management: 

Ramon Gomis (Hospital Clínic de Barcelona, IDIBAPS, 

and CIBERDEM) Field work: Alba Arocas, Laura Esquius, 

Rosario Suarep, María Dolores Zomeño 

Eastern region Field work coordination: Miguel Catalá 

(Hospital Clínico de Valencia and CIBERDEM) CIBERDEM 

Management: Rafael Carmena (Hospital Clínico de Valencia 

and CIBERDEM) Field work: Clara Bixquert, Nieves Brito 

Central region Field work coordination: Alfonso Calle 

(Hospital San Carlos de Madrid) CIBERDEM Management: 

Manuel Serrano Ríos (Hospital San Carlos de Madrid and 

CIBERDEM) Field work: Isabel Alonso, Enrique Mañas 

Southern region Field work coordination: Gemma Rojo 

(Hospital Carlos Haya-IMABIS, Málaga, and CIBERDEM) 

CIBERDEM Management: Federico Soriguer (Hospital 

Carlos Haya-IMABIS, Málaga, and CIBERDEM) Field work: 

Rocío Badía, Isabel Guillén 

Other Steering Committee members Alfonso López Alba 

(Hospital Universitario de Canarias, Tenerife), Elena Bordiu 

(Hospital San Carlos de Madrid), Roser Casamitjana (Hospital 

Clínic de Barcelona, IDIBAPS, and CIBERDEM), Conxa Castell 

(Consell Assessor sobre la Diabetis, Direcció General de Salut 

Pública, Generalitat de Catalunya, Barcelona), Elias Delgado 


21

(Hospital General de Asturias), Edelmiro Menéndez 

(Hospital Universitario Central de Asturias), Josep Franch 

(Centre d’Atenció Primària Raval Sud, Barcelona), José A 

Vázquez (Hospital de Cruces, Bilbao), Sonia Gaztambide 

(Hospital de Cruces, Bilbao, and CIBERDEM), Juan Girbés 

(Hospital Arnau de Vilanova de Valencia), María Teresa 

Martínez Larrad (Hospital San Carlos de Madrid and 

CIBERDEM), Emilio Ortega (Hospital Clínic de Barcelona, 

IDIBAPS, and CIBERDEM), Inmaculada Mora (Hospital 

Universitario de Canarias, Tenerife), Sergio Valdés 

(Hospital Carlos Haya-IMABIS, Málaga, and CIBERDEM), 

and, Joan J Vendrell (Hospital Joan XXIII de Tarragona and 

CIBERDEM) 

In conclusion, this project will provide public health in Spain 

and also the national healthcare system with valuable, relevant 

information about the diabetic community. The Di@bet.es 

Study outcomes will make it possible, for the first time in Spain, 

for the healthcare strategy for this high-incidence disease to 

be more appropriately and coherently designed. ■ 


On October 7th 2010, in the Instituto de Salud Carlos III 

(Madrid), Dr. Federico Soriguer, Director of this initiative, 

presented the implementation and the preliminary results 

coming from this action before both society in general and 

the media. The most noteworthy achievements attained 

up to the presentation of the preliminary results were as 

follows: 

Completion of field work in the remaining areas. During 

the first six months of the year, serum and urine samples 

from individuals participating in the study, along with the 

corresponding demographic, social and clinical data, were 

still being collected. 

Integration of the data from 5,728 participants into a single 

thoroughly cleansed database with the objective of being 

able to obtain accurate conclusions from the study. 

Having the completed Di@bet.es sample collection available 

in the CIBERDEM Biobank (technological platform). From now 

on, this collection can be used by the scientific community in 

relevant studies with high impact on the epidemiology of the 

Spanish population. 

Carrying out statistical analysis on the database including 

information from each individual taking part; thus providing 

both the general public and the scientific community with 

the first preliminary results. 

Having designed and worked on the exploitation strategy of 

the Di@bet.es Study (preparing publications in international 

peer-review journals, presenting projects in response to 

competitive national or international calls derived from this 

initiative, building up international collaborations, among 

other things). 


Although preliminary results were presented in October, 

the project was still ongoing. The conclusive final data, its 

dissemination and exploitation still remained incomplete. In 

order to bring the project to a satisfactory conclusion, much 

collaborative hard work will be required over the coming 

years. CIBERDEM envisages that in the near future, many 

scientific results will stem from the Di@bet.es Study and 

also that new actions will ensue from it. 

22 CibeRdem

CIBERDEM Projects 

Introduction 

CIBERDEM seeks to achieve scientific excellence in 

research and encourage bench-to-bed as well as bed-tobench 

transition (see figures 1 and 2). In order to achieve 

these goals it promotes collaboration between basic and 

clinical research groups to prioritize translational research 

in the network. To this end, 14 initiatives based mainly on 

diabetes and its complications planned to last a year and 

a half have been instituted. CIBERDEM forges synergies 

between its members and launches initiatives that can offer 

an attractive opportunity to build up collaborations with 

other centres outside the consortium, whether national or 

international, because these projects can be seen as a 

pool of scientific knowledge that involves several Spanish 

research groups of excellence in diabetes at the same time. 

Objectives 

To develop scientific actions focused on diabetes and its 

metabolic disorders with a high impact on research. 

To improve collaborations among CIBERDEM researchers, 

mainly among clinical and basic research groups (with a 

minimum participation of 3 research groups at any one time). 

To forge alliances between CIBERDEM researchers through 

joint work on the design and implementation of the projects. 

To demonstrate the competitiveness of CIBERDEM researchers 

and the innovation of their collaborative projects. 

To establish initiatives that a single CIBERDEM research 

group can not embark upon alone. 


14 CIBERDEM initiatives were implemented during 2009- 

2010. The Scientific Director and the Management Office 

followed these projects scientifically and managerially 

right from the outset and the researchers involved in 

the translational research actions worked hard in order 

to achieve successful scientific outputs which were 

disseminated both within and outside CIBERDEM. 

At the CIBERDEM Annual Meeting in 2010, nearly 25% of the 

total oral presentations made focused on the explanation of both 

the work performed and the results obtained in the 14 actions. 

CIBERDEM Projects were also made known to the 

wider national and international scientific community. 

In this regard, oral presentations were made at several 

congresses worldwide. Moreover, many original articles 

were published in international peer review journals such 

as Endocrinology, PNAS, Diabetology and The Journal of 

Clinical Endocrinology and Metabolism (JCEM). 

The merits resulting from the 14 CIBERDEM Projects are 

included in this 2010 Annual Report and can be seen in the 

research outcomes of each research group participating 

in the initiatives. 


In 2011 CIBERDEM aims to continue exploiting the results 

already obtained with the objective of demonstrating the 

impact of the investment that the consortium has made 

in the collaborative translational activity of their research 

groups. During the coming year, the Scientific Director and 

the Managing Director will work together to obtain additional 

Clinical research groups Basic research groups 

funding to continue with these initiatives, hopefully at the 

STEMOB 

3 5 

same level, MODIABor at 

1 

least to a 

3 

similar extent. The expected 

desirable LOWHDL aim is to 2be able to sustain 3 the contribution of 

IODURE 1 4 

these INGENFRED actions to the scientific 

3 

prestige 

1 

of the institution. It is 

important ENDODIAB not to forget 2 that 1the 14 CIBERDEM translational 

DOTUM 1 2 

research 

DIASOBS 

projects have increased 

4 

the 

1competitiveness of 

the CHILDBODYFAT activity of the centre, 2 providing 1 CIBERDEM with more 

opportunities for obtaining funding in the near future, 

from both the public and private sectors, always with the 

objective of assigning it to CIBERDEM diabetes research. 

NEURONET-DIAB 

METADIAB 

IREVAS 

GIDIPRED 

ANTIBETACELL 

Basic research groups 

Clinical research groups 

2 1 

1 2 

2 1 

1 2 

2 1 

Figure 1. CIBERDEM bench to bed projects (NEURONET-DIAB, 

METADIAB, IREVAS, GIDIPRED, ANTIBECELL) showing the number 

of research groups participating in each project (in green the 

groups with a basic profile, in red those with a clinical profile). 

STEMOB 

MODIAB 

LOWHDL 

IODURE 

INGENFRED 

ENDODIAB 

DOTUM 

DIASOBS 

CHILDBODYFAT 

Clinical research groups 

3 5 

1 3 

2 3 

1 4 

3 1 

2 1 

1 2 

4 1 

2 1 

Basic research groups 

Figure 2. CIBERDEM bed to bench projects (STEMOB, MODIAB, 

LOWHDL, IODURE, INGENFRED, ENDODIAB, DOTUM, DIASOBS, 

CHILDBODYFAT) showing the number of research groups participating 

in each project (in red the groups with a clinical profile, in 

green those with a basic profile). 

Basic research groups Clinical research groups 

NEURONET-DIAB 

METADIAB 

IREVAS 

GIDIPRED 

ANTIBETACELL 

2 1 

1 2 

2 1 

1 2 

2 1 


23

The 14 Projects 

The influence of insulin resistance states and their 

compensatory mechanisms by endocrine pancreas on 

endothelial/vascular damage. IREVAS 

Inflammation associated with obesity and type 2 

diabetes mellitus, with insulin resistance as a common 

pathophysiological feature, produces qualitative and 

quantitative changes in the sub-endothelium. Thus, the 

objective of this study is to investigate the contribution of 

insulin resistance to endothelial/vascular damage, with or 

without the added complications of obesity. 

Groups: Manuel Benito, Deborah Burks, Ramon Gomis 

Project coordinator: Manuel Benito 

Identification of neurodegenerative mechanisms that 

promote the development of diabetic retinopathy: the role 

of insulin signalling and apoptosis. NEURONET-DIAB 

The molecular mechanisms which mediate the development 

of diabetic retinopathy (DR) remain unknown. Insulin and 

IGF-I signalling play important roles in the development and 

survival of retinal cells. Our hypothesis is that resistance to 

insulin/IGF-I in the retina disables the molecular mechanisms 

which protect retinal cells against stress and apoptosis, 

thereby triggering neurodegeneration and DR. The results 

will provide a rational basis for developing novel strategies to 

detect, prevent and treat DR in its earliest stages. 

Groups: Deborah Burks, Ángela Martínez Valverde, Rafael Simó 

Project coordinator: Deborah Burks 

Cooperative population and database studies for 

genetic association analysis in T2DM and related traits. 

INGENFRED 

Type 2 diabetes mellitus (T2DM) is a complex disease 

resulting from the interaction of environmental and genetic 

factors. The genetics of several functional systems in T2DM 

have not been dissected. The project aims to develop 

genetic T2DM studies, integrating different populations and 

databases, considering the interaction between genetic 

and environmental factors with the aim of developing future 

projects that will ultimately lead to clinical applications. 

Groups: Rafael Carmena, Francisco Blanco Vaca, Manuel 

Serrano Ríos, Federico Soriguer 

Project coordinator: Felipe Javier Chaves 

Clinical, genetic and functional characterization of 

monogenic diabetes: from the bench to the bedside. 

MODIAB 

Monogenic diabetes (MD) accounts for 1-2% of diabetes cases 

and is often misdiagnosed. Knowledge of the genetic aetiology 

of diabetes enables better treatment, prediction, disease 

progression, screening of relatives and genetic counselling. 

The project aims to determine aspects such as new genetic 

causes of MD, novel functional information for pancreatic beta 

cells and the importance of new regulatory sequences through 

the discovery of mutations in known genes. 

Groups: Luis Castaño, Enrique Blázquez, Jorge Ferrer, 

Mario Vallejo 

Project coordinator: Luis Castaño 

Diabetes and obesity treatment by tungstate: metabolic 

and molecular targets. DOTUM 

The plastic capacity of the pancreas to adapt to the 

metabolic necessities of the organism plays a key role in 

type 2 diabetes. This project aims to unravel the mechanisms 

controlling beta-cell plasticity; to dissect and determine the 

key players in the processes that adjust functional beta-cell 

mass; and to identify the role that peripheral tissues and the 

central nervous system play in plasticity control. Another 

goal is to work towards new therapeutic strategies through 

the analysis of several procedures such as the study of 

phosphatase inhibitors, for example, sodium tungstate. 

Groups: Ramon Gomis, Xavier Correig, Joan J Guinovart 

Project coordinator: Ramon Gomis 

Determinants of insulin resistance and glucose tolerance 

disorders (including diabetes) in severe obesity and their 

changes after bariatric surgery-induced weight loss. 

DIASOBS 

Obese patients submitted to bariatric surgery present a 

marked weight loss that frequently normalizes abnormalities 

in glucose tolerance because obesity is the major risk 

factor for this kind of disorder. This project focuses on the 

identification of risk factors for insulin resistance, abnormal 

glucose tolerance and diabetes in severely obese patients, 

as well as on the identification of the determinants of the 

resolution of these disorders following the marked and 

sustained weight loss usually attained after bariatric surgery. 

Groups: Héctor F Escobar Morreale, Xavier Correig, Eduard 

Montanya, Rafael Simó, Joan J Vendrell 

Project coordinator: Héctor F Escobar Morreale 

Glycogen-induced dysfunctions in the pancreas and retina 

and their involvement in the ethiogenesis of diabetes 

mellitus. GIDIPRED 

The project is based on the idea that, contrary to the general 

belief which considered glycogen to be beneficial for cells, 

the deposition of glycogen may be deleterious for certain 

cell types. The aim is to study the alterations induced by 

this abnormal accumulation in pancreatic beta cells, 

neurons, and retinal cells. The working hypothesis is that 

the accumulation of this polysaccharide in these cell types 

contributes to the induction of apoptosis and therefore 

the pathological consequences associated with diabetes 

mellitus, namely reduced insulin secretion and retinopathy. 

Groups: Joan J Guinovart, Ramon Gomis, Rafael Simó 

Project coordinator: Joan J Guinovart 

Body fat amount and distribution in childhood determines 

predisposition to type 2 diabetes. CHILDBODYFAT 

Treatment with insulin sensitizing agents in SGA-catchup 

24 CibeRdem

girls (girls born small for gestational age who show 

spontaneous catchup weight during childhood) improves 

insulin resistance, body fat excess and the adipokine 

pattern. The project aims to determine whether metformin 

can also revert these abnormalities in boys and in younger 

SGA children and whether it may directly influence specific 

lipolytic molecules or target the transcription factors 

involved in their expression. 

Groups: Lourdes Ibáñez, Xavier Correig, Lluís Masana 

Project coordinator: Lourdes Ibáñez 

The production of monoclonal antibodies which selectively 

react with cell surface molecules on human pancreatic 

beta cells. ANTIBECELL 

So far, it has not been possible to obtain an antibody that 

recognizes human beta cells, although the identification of 

these pancreatic cells in vitro and in vivo is highly desired. In 

this project we propose a novel immunization strategy making 

it possible to obtain immune response against antigens 

expressed poorly and to search for antibodies against 

receptors on the cell surface of pancreatic beta cells. The 

objective achievement opens new perspectives for studies in 

regeneration, development and cell therapy using islets. 

Groups: Franz Martín, Eduard Montanya, Angel Nadal 

Project coordinator: Juan Tejedo 

Characterization of low HDL syndrome in type 2 diabetes. 

LOWHDL 

Macrovascular risk in type 2 diabetes mellitus patients, after 

receiving proper LDL-lowering therapy, is inappropriately 

high. This is partly attributed to the low HDL levels. 

Moreover, some drugs which raise HDL levels have failed to 

reduce the cardiovascular risk. Thus, LOWHDL mainly aims 

to characterize the HDL subclasses in T2DM patients both 

quantitatively and qualitatively and to study the impact of 

HDL increasing drugs on HDL qualitative changes. 

Groups: Lluís Masana, Francisco Blanco Vaca, Rafael 

Carmena, Xavier Correig, Manuel Vázquez Carrera 

Project coordinator: Lluís Masana 

Comparative metabolomic analysis for the detection of 

biomarkers in diabetes. METADIAB 

In METADIAB, metabolomics is used to determine, thanks 

to the information provided by the endogenous metabolite 

profile, which metabolites are altered in diabetes. The 

changes that we aim to study are the consequences 

produced by high concentrations of glucose and lipids 

(glucolipotoxicity) in the islet pancreatic metabolome. 

Another aspect in which we are interested is the evaluation 

of the metabolomic effects induced by physical exercise 

in both type 1 and 2 diabetes mellitus. As a result, we will 

improve our knowledge in these situations and discover 

candidate biomarkers of the disease. 

Groups: Xavier Correig, Ramon Gomis, Anna Novials 

Project coordinator: Xavier Correig 

Mechanisms of endothelial dysfunction in diabetes: the 

role of amylin and circulating endothelial cells. ENDODIAB 

The main aetiology for death and for a high percentage of 

morbidity in patients with diabetes is vascular disease. Thus, 

this project aims to investigate circulating endothelial cells 

(CECs) as markers of endothelial dysfunction in diabetic 

patients; to determine the role of amylin in endothelial function; 

and to investigate the presence of preclinical atherosclerosis 

by assessing endothelial function in patients with type 1 

diabetes mellitus, type 2 diabetes mellitus and obesity. 

Groups: Anna Novials, Ramon Gomis, María Luisa 

Villanueva Peñacarrillo 

Project coordinator: Anna Novials 

The impact of overnutrition, diabetes-obesity and 

undernutrition on the regulation of energy homeostasis 

in the central nervous system. From animal models to 

humans. IODURE 

Increasing evidence suggests that the central nervous 

system plays a crucial role in regulating energy homeostasis 

through crosstalk with adipose tissue and the endocrine 

pancreas. The objective of the project is to investigate 

how the brain reacts to metabolic challenges associated 

with overnutrition, diabetes-obesity and undernutrition. 

It is expected that novel mechanisms responsible for the 

dysregulation of energy homeostasis which leads to obesity 

and diabetes will be identified. 

Groups: Manuel Serrano Ríos, Carmen Álvarez, Enrique 

Blázquez, Deborah Burks, Mario Vallejo 

Project coordinator: Manuel Serrano Ríos 

Adult adipose tissue-derived progenitor cells: the 

influence of the clinical phenotype and adipose depot 

origin in their biological properties. STEMOB 

The objective of this project is to test for differential behaviour 

in adult pre-adipocytes and adipocytes derived from 

adipose tissue mesenchymal stem cells (ad-MSC) obtained 

from lean and obese subjects and also to characterize 

adipose derived cells from a molecular and lipidomic 

perspective. The expected result is the identification of the 

differences in adMSC (from subcutaneous and visceral 

depots) that exist between lean and obese subjects. 

Groups: Joan J Vendrell, Jesús Balsinde, Anna Maria 

Gómez Foix, Sonia Fernández Veledo, Eduard Montanya, 

Rafael Simó, Manuel Vázquez Carrera, Antonio Zorzano 

Project coordinator: Joan J Vendrell ■ 


25

Technological platforms 

Biobank 

Metabolomics Platform

Biobank 

Introduction and objectives 

The CIBERDEM Biobank is a scientific and technological 

platform which coordinates the collection, processing, 

storage and retrieval of biological samples in the field of 

diabetes and other metabolic diseases, which may then 

be utilized by CIBERDEM research groups and by other 

scientific institutions in their experiments and projects. The 

Biobank, thanks to its experience and expertise in this field, 

holds one of the most important collections of samples of 

metabolic disorders in southern Europe, bringing great 

added value to the biomedical research conducted by 

CIBERDEM. Structured into nodes with multiple collection 

and processing sites, the Biobank allows for the immediate 

storage of samples following blood extraction in order to 

ensure the highest quality possible. Through the centralized 

coordination of sample management, the Biobank also 

ensures the traceability of its samples, as required by 

the recently passed Biomedical Research Act. The 

Coordinating Node of the CIBERDEM Biobank obtained the 

ISO9001 quality certification in December 2009. 

Scientific services 

The main services provided by the Biobank consist of the 

following: 

Design and management of a large metabolic disorder 

sample collection, involving donor recruitment; data 

registration; informed consent management; serum and 

plasma storage; DNA purification and storage; lymphocyte 

isolation and immortalization; and quality management. 

Assurance of traceability. 

Quality control of the stored samples. 

Organization of an internal database for the analysis of 

samples and data. 

Management of sample request proposals through the 

coordination of the Scientific External Committee and the 

Ethics Committee. 

Personalized assistance in sample management. 

Coordinating Node 

IDIBAPS, Barcelona: Principal Investigators Ramon Gomis, 

Anna Novials Coordinator Anna Bosch Associate researcher 

Laura Brugnara Lab technician Anna Morales Lab manager 

Albert Davins Lab technician and quality control manager 

Roser Mas Nurse Laura Tugores 

Nodes 

Hospital Joan XXIII, Tarragona: Principal Investigator Joan 

Vendrell Research assistant Lluís Gallart Lab technician 

Miriam Campos 

www.clinicbiobanc.org 

Hospital Sant Joan, Reus: Principal Investigator Lluís 

Masana Research assistants Jordina Saladié, Jordi Merino 

Lab technician Carme Buixadera 

Hospital de Cruces, Barakaldo: Principal Investigator Luis 

Castaño Research assistant and lab manager Inés Urrutia 

Research assistant and dietician Teba González 

Hospital Clínico San Carlos, Madrid: Principal Investigator 

Manuel Serrano Ríos PhD student Carina Zabena Lab 

technician Mari Carmen Obiang 

Hospital Civil, Málaga: Principal Investigator Federico 

Soriguer Associate researcher Gemma Rojo Research 

assistant Francisca Linares Nurse Mª José Moreno 

Hospital Clínico, Valencia: Principal Investigator Rafael 

Carmena Associate researcher Javier Chaves Research 

assistant Esther Benito Lab technician Verónica González 

Hospital de Sant Pau, Barcelona: Principal Investigator 

Francesc Blanco Vaca Associate researcher Jesús Martín 

Lab technician and Nurse Cristina Martín 

Facilities 

The Coordinating Node of the Biobank centralizes the 

organization of Biobank sample management and is thus 

endowed with the most advanced technology available 

for this purpose: automated DNA extraction platform 

(Chemagen system, magnetic beads); liquid handling 

station (Tecan EVO150), cell immortalization facility 

(P2 level safety lab); liquid nitrogen tanks; continuous 


27

monitoring of environmental conditions from storage 

systems; -150ºC freezers; bar-code readers and printers; 

nanodrop spectrophotometer; and nitrogen and cryogen 

free controlled rate freezers. 

The Biobank is equipped with the following facilities within 

each node, permitting the immediate storage of samples 

taken: -80ºC freezers; micronic system for the storage of 

the samples in standardized aliquots; and web-based IT 

infrastructure. 


During 2010, the Biobank collected samples from more 

than 1,000 new donors affected by the most widespread 

metabolic diseases in Spain: type 1 diabetes, type 2 

diabetes, dyslipidaemias, obesity, and morbid obesity. 

As previously established, all of the donors completed 

an extensive questionnaire with personal clinical data, 

demographic information, and exercise and food habits, 

which have been entered into the Biobank clinical database. 

These data, together with their corresponding samples, 

represent one of the most exhaustive collections available 

for the study of metabolic disorders. Overall, the Biobank 

freezers and tanks stored more than 100,000 aliquots, 

which were coded and registered in a specially designed 

database. 

As the sample and data repository has achieved a 

considerable size, several groups from CIBERDEM have 

decided to request samples for their research projects. 

Most of them used DNA, but serum, plasma or PBMCs 

were also supplied. 

The BCGene database, which provides a professional, 

secure data warehouse for the clinical and research data, 

has been successfully implemented in 2010 in all the 

participating nodes. This database, physically located 

in the IDIBAPS servers, hosts demographic, clinical, and 

analytical data associated to the Biobank samples. The webbased 

architecture of the database offers secure access 

to all the Biobank nodes, guarantees donor confidentiality 

and ensures sample traceability. Data access is provided 

by the data manager once a request has been made to the 

Biobank Committees. 

Another great achievement of 2010 was the integration 

of more than 5,000 donors from the Di@bet.es Study 

into the Biobank. In total, this meant the incorporation of 

more than 80,000 aliquots of serum and blood which are 

now available to research projects. These samples are 

especially precious due to the quality of the associated 

data. 


Now that the Biobank has been established and consolidated, 

the main goal for the next year is to provide as many samples 

as possible in order to facilitate projects of outstanding quality 

which could not be carried out without the collaboration of 

different sample providers. 

The other objective will be to perform whole genome 

amplification of the DNA obtained from the donors included in 

the Di@bet.es Study. This amplified DNA will be available for 

genetic and genomic studies once a request has been made 

to the Biobank Committees. ■ 

3500 

2010 

3000 

2009 

2008 

2500 

2000 

1500 

1000 

500 

0 

Diabetes Type 1 Diabetes Type 2 Obesity Morbid Obesity Dyslipidemia MODY Diabetes Di@bet.es Study 

Number and type of samples available from the CIBERDEM Biobank, 2008-2010. 

28 CibeRdem


Introduction and objectives 

The Metabolomics Platform is a joint research facility created 

by the URV (Universitat Rovira i Virgili, Tarragona, Spain) 

and CIBERDEM. The mission of the Metabolomics Platform 

is to offer metabolomic services to the biomedical and 

clinical research community of both CIBERDEM and the 

URV. The main objective of the Metabolomics Platform is to 

work as an integrative facility and act as a consulting site 

which becomes fully involved in the metabolomics-related 

experiments proposed by the groups. Our collaboration starts 

with the defining of goals, dimension and characteristics of 

the sample set, as well as experiment design. Later on, the 

raw data is processed by our team and we are involved in the 

interpretation of the results, delivering sound, significant and 

useful clinical conclusions for the different research groups. 

The equipment currently available in high field NMR, and MS 

(GC-single quad, LC-TOF and LCQqQ) allows high throughput 

analytical measurements of body fluids (i.e., serum and urine) 

as well as tissues or biopsies from humans and/or animal 

models (rats, mice, etc). The use of advanced statistical, 

chemometric, multivariate and artificial-intelligence algorithms 

allows us to turn large measurement datasets into metabolic 

fingerprinting or profiling results, and ultimately into useful 

clinical information. Our goal is to introduce metabolomics as 

a potential tool for clinical diagnostics and elucidate unknown 

mechanisms associated with disease. The Metabolomics 

Platform is particularly addressed to the needs of CIBERDEM 

and URV groups, however, its services and potential scientific 

collaborations are available to other biomedical research 

groups in Spain and worldwide. 

Coordination 

Principal Investigator Xavier Correig Associate researchers 

Jesús Brezmes, Nicolau Cañellas Research assistants Miguel 

Ángel Rodríguez, Maria Vinaixa, Antoni Beltran 

www.metabolomicsplatform.com 

Scientific services 

Name Principle Application 

1H-NMR rat/ 

mouse liver 

profiling 

1H-NMR rat/ 

mouse brain 

profiling 

Identification 

and (relative) 

quantification 

of up to 52 

metabolites from 

aqueous and 

lipid extracts 



quantification of 

64 metabolites 

from aqueous 

and lipid 

extracts 

Phenotyping of geneticallymodified 

animals. Drug toxicity 

and pre-clinical drug candidate 

safety assessment. Biomarker 

discovery. Clinical studies 

(diagnosis and therapeutic 

efficacy). Monitoring of dietrelated 

health phenotyping 

Drug neurotoxicity and 

pre-clinical drug candidate 

safety. Neurotoxicity studies 

Scientific equipment 

The Platform currently manages and has full access to the 

following NMR technology: 

600 MHz Bruker Avance III + cryoprobe + ScanJet 

500 MHz Bruker Avance III + HR-MAS probe 

The Rovira i Virgili University shares three mass 

spectrometers with the Metabolomics Platform, which 

means limited access of our personnel to the following 

technology: 

LC ESI-TOF 

LC ESI-QqQ 

GC-single quad 

1H-NMR serum/ 

plasma extract 

profiling 

1H-NMR urine 

extract profiling 

Identificacion 



of up to 47 

metabolites 

from serum/ 

plasma extracts 

of human/ 

animal models 




of up to 46 

metabolites in 

human/animal 

model urine 

Biomarker discovery. 

Clinical studies (diagnosis 

and therapeutic efficacy). 

Monitoring of diet-related 

health phenotyping 


Assessment of diet or 

drug intervention. Drug 

toxicology studies. Clinical 

studies (diagnosis and 

therapeutic efficacy) 


29

HR-MAS 

1H-NMR of 

biopsies, tissues 

or cell cultures 

GC-MS 

untargeted 

metabolomics 

on serum, urine 

or tissue extract 

samples 

LC-MS 

untargeted 

metabolomics 

on serum, urine 

or tissue extract 

samples 

Targeted LC-MS 

metabolomics 

Statistics and 

multivariate 

analysis 

Metabolic 

fingerprinting 

and profiling of 

intact non-solid/ 

non-liquid 

biological 

samples 


of features that 

are differently 

expressed in 

cases vs. control 

experiments and 

identification of 

key metabolites 


of features that 

are differently 

expressed in 

cases vs. control 

experiments and 

identification of 

key metabolites 

Detection and 

quantification of 

predetermined 

metabolites 

in biofluids or 

sample extracts 

Programming 

and 

implementation 

of supervised 

and 

unsupervised 

multivariate 

algorithms in 

metabolomics 

datasets 

Clinical diagnostic. 

Biomarker discovery 




Assessment of diet interventions 




Assessment of diet interventions 

Phenotypic and physiological 

effects. Pre-clinical drugcandidate 

safety assessment. 

Pharmaco-metabonomics. 

Disease diagnosis and 

therapeutic efficacy 

Basic univariate statistical tests. 

Using advanced multivariate and 

artificial intelligence algorithms 

for metabolomics data sets and 

turning them into useful clinical 

information (PCA, PLS-DA, 

ANNs). Identifying metabolic 

relationships, mechanisms, 

functions and pathways in 

experimental data and mapping 

of relevant pathways 


The Metabolomics Platform, inaugurated in June 2008, is 

now able to offer a complete set of NMR- and MS-based 

metabolomic services to CIBERDEM groups. During 

2010, the Metabolomics Platform worked on 5 intramural 

CIBERDEM collaborations in the areas of diabetic 

dyslipaemias, insulin resistance related to polycystic 

ovarian syndrome, and diabetes and exercise. In 2010, 

the Platform began 12 projects with CIBERDEM groups 

and other institutions in the areas of nutrition and health, 

metabolomic experiments with cell cultures, phenotyping of 

animal models, and so on. The number of serum samples 

processed was over 2500 (199 serum/plasma samples + 

300 tissues extract samples + 200 cell cultures samples + 

100 urine samples). 


In October 2010 the URV was declared Regional Campus 

of Excellence by the Ministry of Education, and has 

received a 4M € loan from the INNOCAMPUS programme 

to purchase scientific equipment for the new Centre for 

Omics Science. Approximately 3M € will be dedicated 

to state-of-the-art mass spectrometry technology for 

metabolomics and proteomics. In January 2011, CIBERDEM 

and the Metabolomics Platform welcomed Dr Oscar 

Yanes as scientific coordinator of the Platform. Dr Yanes 

has extensive experience in mass-spectrometry-based 

metabolomics and significant publications to his name 

in high-impact-factor journals including Nature, Nature 

Chemical Biology, the Journal of Clinical Investigation and 

Analytical Chemistry. He arrived from the Scripps Center for 

Metabolomics and Mass Spectrometry (La Jolla, California) 

which is headed by Dr Gary Siuzdak. ■ 

For more information see page 36. 

Metabolomics Platform NMR-equipment: the 500 and 600 MHz 

NMR systems can be seen on the left and right, respectively. 

30 CibeRdem

Area 1 

Insulin signalling and resistance 

Role in the onset of diabetes 

Total IF: 119.26 

Publications: 19 

7 of them in the first decile 

10 in the first quartile and 

2 in the second quartile 

With other CIBERDEM groups: 4 

With other CIBERs: 1 

Research grants (through associate institutions): 24 

Scientific collaborations within CIBERDEM: 13 

PhD theses: 5

In 2010, we deeply regret the loss of Margarita Lorenzo, one of our group’s leaders. Her lab did outstanding work 

unravelling the molecular mechanisms of insulin resistance in brown adipocytes and skeletal muscle cells. Indeed, her 

enthusiasm and creativity will always form part of our collective memory. 

Our main ongoing concern is to persevere in the identification of novel insulin resistance and type 2 diabetes susceptibility 

genes which may control metabolic homeostasis in insulin resistance. We are also continuing with our study of glycogen 

metabolism mechanisms in the liver and skeletal muscle and their alterations in diabetes mellitus. We are still unravelling 

the molecular mechanism of insulin resistance in a tissue-specific manner to develop new cellular models in relation to 

major insulin target tissues. Finally, we continue to develop new mouse models of insulin resistance, type 2 diabetes and 

obesity, studying their metabolic alterations and vascular complications. 

Among our achievements in 2010, regarding glycogen metabolism, we demonstrated the role played by reconstitution 

with glycogen phosphorylase isoforms in cultured muscle from patients with McArdle’s disease carrying mutations, the 

contribution of hepatic overexpression of a constitutively active form of liver glycogen synthase on glucose homeostasis 

and the defective activation of skeletal muscle PGC-1{alpha}/Mitofusin-2 in subjects with early-onset type 2 diabetes. 

Regarding liver metabolism, we demonstrated how inhibition of PTP1B restores IRS1-mediated hepatic insulin signalling in 

IRS2-deficient mice and we also described the contribution of dietary cholesterol in the development of fatty liver disease. 

As regards skeletal muscle, we demonstrated the role played by G protein-coupled receptor kinase 2 in insulin resistance 

and obesity. Finally, in respect of the mechanisms involved in the development of beta cell mass and the compensatory 

mechanisms for peripheral insulin resistance, we have clearly shown that TSC1-TSC2 complex integrates insulin and 

glucose signalling involved in pancreatic beta-cell proliferation. 

Manuel Benito 

CIBERDEM Scientific Area Coordinator 


33

Diabetes and cardiovascular 

Facultad de Farmacia, Universidad Complutense de Madrid 

www.ucm.es/info/biomol2/ 

Principal Investigator Manuel Benito benito@farm.ucm.es Associate researchers Óscar Escribano, Almudena Gómez, Carlos Guillén 

Postdoctoral fellow Beatriz Gozalbo PhD students Alberto Bartolomé, Liliana Perdomo, Yolanda Fernández Otero Lab manager Gema 

García Lab technician Silvia Fernández 


Publications: 1, in the first quartile 

Research grants: 2 

National projects: 1 

Autonomous Community projects: 1 


PhD theses: 1 

Keywords 

Beta-cell signal transduction. Insulin sensitivity and 

resistance. Weight regulation and obesity. Macrovascular 

disease. Pathogenic mechanisms. 

-BATIRKO and BATIRKO/apoE -/- DKO mice: Role of the 

compensatory mechanisms of insulin resistance in the 

aggravation/attenuation of inflammation, oxidative stress 

and vascular lesion in the aorta. 

-The role of TSC1/TSC2 in the integration of insulin and 

glucose signalling involved in beta-cell proliferation: 

regulation of ER-stress and autophagy. 

-Molecular mechanisms of insulin resistance in 

cardiomyocytes. 

-Molecular mechanism of insulin resistance in aortic 

endothelial cells. 

-Molecular mechanism of insulin resistance in aortic smooth 

muscle vascular cells. 

Main lines of research 

-Inducible insulin receptor liver-specific knockout (iLIRKO): 

a mouse model for the study of insulin resistance, betacell 

hyperplasia and vascular dysfunction in response to 

hyperinsulinaemia. 

Publications* 

Original article 

Role of the TSC1-TSC2 complex in the integration of insulin and 

glucose signaling involved in pancreatic beta-cell proliferation 

Bartolomé A, Guillén C, Benito M 

*Only those published in 2010, with CIBERDEM listed among the affiliations, which are related to CIBERDEM’s field of research and are 

located in the first or second quartile of their subject category are included. 

34 CibeRdem

Endocrinology, 151, 3084-3094 (2010) 

IF: 4.752 first quartile 

Research grants 

National project 

Modelos animales y celulares de resistencia a la insulina: 

daño cardiovascular 

Ministerio de Ciencia e Innovación, SAF2008-00031: 2009- 

2011 

Principal Investigator: Manuel Benito 

Autonomous Community project 

Diabetes y cardiovascular (group 920384) 

CAM/UCM, gr58/08: 2009-2010 

Principal Investigator: Manuel Benito 

Scientific collaborations within CIBERDEM 



endothelial/vascular damage 

IREVAS: 2009-2010 

Coordinator: Manuel Benito 

CIBERDEM groups: M Benito, D Burks, R Gomis 

PhD theses 

Lipoatrofia marrón, obesidad y daño vascular 

Author: Yolanda Fernández Otero 

Thesis advisors: Manuel Benito, Almudena Gómez 

University: Universidad Complutense de Madrid 

Thesis defense date: November 2010 ■ 

Searching the endocrine pancreas: Picking up beta islets. 


35


Universitat Rovira i Virgili, Institut d’Investigació Sanitària Pere Virgili, Tarragona 

www.metabolomicsplatform.com 

Principal Investigator Xavier Correig xavier.correig@urv.cat Associate researchers Jesús Brezmes, Nicolau Cañellas Research assistants 

Miguel Ángel Rodríguez, Maria Vinaixa, Antoni Beltran PhD students Roger Mallol, Sara Samino, Josep Gómez 


Publications: 1, in the first decile 




Awards: 1 

Keywords 

Lipids, lipoproteins. Metabolomics. Bioinformatics. 

Biomarkers and Imaging. 


-NMR lipoprotein characterization for the study of 

dyslipidaemias. 

-Serum profiling method for the study of insulin resistance 

and diabetes in population studies. 

-The development and study of advanced statistical, 

chemometric, multivariate and artificial intelligence 

algorithms which will allow large measurement datasets. 

-Non-radioactive isotopomers for the study of metabolic 

profiling and its flux in cultured cells and animal models. 

Publications* 


Metabolomic assessment of the effect of dietary 

cholesterol in the progressive development of fatty liver 

disease 

Vinaixa M, Rodríguez MA, Rull A, Beltrán R, Bladé C, 

Brezmes J, Cañellas N, Joven J, Correig X 

J Proteome Res, 9, 2527-2538 (2010) 

IF: 5.132 first decile 


National projects 

Neurodegeneración en la patogénesis de la retinopatía 

diabética incipiente. Estudio de los mecanismos 

implicados a través de un abordaje integrado de biología 

de sistemas 



36 CibeRdem

Ministerio de Ciencia e Innovación, SAF 2009-07408: 

2009-2011 

Principal Investigator: Rafael Simó 

Associate investigator: Miguel Ángel Rodríguez 

CIBERDEM groups: X Correig, R Simó 

Dislipemia aterógena de la obesidad, síndrome metabólico 

y diabetes tipo 2: caracterización metabólica y mecanismos 

patogénicos 

FIS, PI081409: 2008-2011 

Principal Investigator: Lluís Masana 

Associate investigator: Jesús Brezmes 

CIBERDEM groups: X Correig, L Masana 

Awards 

Best Poster of the Conference: An integrated 1H NMR, GC- 

MS and HPLC-(ESI/TOF) based metabolomics approach to 

the study of acute exercise in human serum metabolome 

(2010) 

Institution: Advances in Metabolic Profiling Conference and 

Exhibtion 

Awardee: Antoni Beltran ■ 

For more information see page 29. 

Caracterización bioquímica, metabólica y genética de la 

hipertrigliceridemia asociada a alto riesgo cardiovascular 

FIS, PI081579: 2008-2011 

Principal Investigator: Josep Ribalta 

Associate investigator: Nicolau Cañellas 

CIBERDEM groups: X Correig, L Masana 



predisposition to type 2 diabetes 

CHILDBODYFAT: 2009-2010 

Coordinator: Lourdes Ibáñez 

CIBERDEM groups: X Correig, L Ibáñez, L Masana 


disorders, including diabetes, in severe obesity 

and their changes after bariatric surgery-induced 

weight loss 

DIASOBS: 2009-2010 

Coordinator: Héctor F Escobar Morreale 

CIBERDEM groups: X Correig, E Montanya, HF Escobar 

Morreale, R Simó, J Vendrell 

A Score PCA diagram showing the distribution of lipoprotein 

profiles. 


and molecular targets 

DOTUM: 2009-2010 

Coordinator: Ramon Gomis 

CIBERDEM groups: X Correig, R Gomis, JJ Guinovart 

Characterization of low HDL syndrome in type 2 

diabetes 

LOWHDL: 2009-2010 

Coordinator: Lluís Masana 

CIBERDEM groups: X Correig, F Blanco Vaca, R Carmena, 

L Masana, M Vázquez Carrera 


biomarkers in diabetes 

METADIAB: 2009-2010 

Coordinator: Xavier Correig 

CIBERDEM groups: X Correig, R Gomis, A Novials 

GC-MS and NMR-based metabolomics monitoring of glycolysis 

and TCA cycle intermediates. 


37

Obesity, inflammation and insulin resistance 

Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense de Madrid 

www.ucm.es 

Principal Investigator Sonia Fernández Veledo sonia.fernandezveledo@gmail.com Postdoctoral fellows María Alonso, Iria Nieto 

PhD students Lucía García, Ana Vázquez, Rocío Vila Lab technician Loa Muñoz Administrative staff Elena González 


Publications: 2, 1 in the first decile and 1 in the first quartile 





PhD theses: 2 

Awards: 2 

Keywords 

Cytokines. Exercise. Glucose transport. Insulin sensitivity 

and resistance. Lipid metabolism. 


-Insulin resistance induced by cytokines such as TNFalpha, 

IL-6, IL-1 beta or leptin and hyperisulinaemia in 

murine and human muscle and adipose cells. Studies on 

mice are also being performed. 

-The study of glucose homeostasis and insulin sensitivity in 

GRK-2 heterozygous mice. 

-The contribution of PTP1B to insulin action on glycogen 

metabolism in myocytes: PTP1B as a target for the 

prevention and treatment of insulin resistance. 

-Pharmacological approaches such as treatment 

with PPAR and LXR agonists which overcome insulin 

resistance. 

Publications* 

Original articles 

Adenosine 5’-monophosphate-activated protein kinasemammalian 

target of rapamycin cross talk regulates brown 

adipocyte differentiation 

Vila-Bedmar R, Lorenzo M, Fernández-Veledo S 



G protein-coupled receptor kinase 2 plays a relevant role in 

insulin resistance and obesity 



38 CibeRdem

Garcia-Guerra L, Nieto-Vazquez I, Vila-Bedmar R, Jurado- 

Pueyo M, Zalba G, Díez J, Murga C, Fernández-Veledo S, 

Mayor F Jr, Lorenzo M 

Diabetes, 59, 2407-2417 (2010) 


2nd prize of IDOF Annual Meeting (2010) 

Institution: Institute of Diabetes and Obesity Forum 

Awardees: Rocío Vila Bedmar, Sonia Fernández Veledo, 

Lucía García Guerra, Iria Nieto Vázquez ■ 



Mecanismos que conectan la inflamación asociada a la 

obesidad con la resistencia a la insulina 

MICINN, BFU2008-04043: 2009-2011 

Principal Investigator: Sonia Fernández Veledo 

Inflamación asociada a obesidad y resistencia a insulina: 

papel de quinasas, fosfatasas y desacetilasas 

Banco Santander Central Hispano/UCM, GR58/08: 2009-2010 



Redes de señalización celular en enfermedades de 

etiología inflamatoria 

INSINET-CM network, S-SAL/0159/2006: 2007-2010 



Adult adipose tissue-derived progenitor cells: the influence 

of the clinical phenotype and adipose depot origin on their 

biological properties 

STEMOB: 2009-2010 

Coordinator: Joan J Vendrell 

CIBERDEM groups: S Fernández Veledo, J Vendrell, A Zorzano, J 

Balsinde, AM Gómez Foix, E Montanya, R Simó, M Vázquez Carrera 

PhD theses 

Mecanismos moleculares implicados en la diferenciación 

y termogénesis del tejido adiposo marrón: AMPK y GRK2 

como potenciales dianas terapéuticas para el tratamiento 

de la obesidad 

Author: Rocío Vila Bedmar 

Thesis advisors: Margarita Lorenzo, Sonia Fernández Veledo 


Thesis defense date: November 17, 2010 

Implicación de GRK2 en el proceso miogénico. Identificación 

de una nueva diana para el tratamiento de la resistencia a 

insulina y la obesidad 

Author: Lucía García Guerra 

Thesis advisors: Margarita Lorenzo, Iria Nieto Vázquez 


Thesis defense date: October 15, 2010 

Awards 

Colegio Oficial de Farmacéuticos de Madrid (2010) 

Institution: Real Academia Nacional de Farmacia 

Awardees: Lucía García Guerra, Iria Nieto Vázquez 

Insulin signalling is regulated by GRK2 levels by a mechanism involving 

the formation of dynamic GRK2/IRS1 complexes. 


39

Mechanisms of control of glucose and 

fatty acid metabolism in skeletal muscle cells 

and metabolic impairment in atrophy 

Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona 

www.bq.ub.es 

Principal Investigator Anna Maria Gómez Foix agomezfoix@ub.edu Associate researcher Cèlia García Martínez Research assistants Maria 

Guitart de la Rosa, Marta Montori Grau PhD students Emma Mormeneo Beltran, Oscar Osorio Conles Lab manager Anna Orozco García 


Publications: 3, 1 of them in the first decile and 2 in the first quartile 



With other international groups: 1 





Keywords 

Insulin sensitivity and resistance. Lipid metabolism. 

Carbohydrate metabolism. 


-Mechanisms of control of skeletal muscle glycogen 

metabolism. Differential functionality of the protein 

phosphatase 1 (PP1) glycogen-associated regulatory 

subunits present in human skeletal muscle GM (PPP1R3A), 

PTG (PPP1R3C) and PPP1R6 (PPP1R3D). 

-Metabolic control role of the fatty acid transport protein 

1 (FATP1) in muscle and deleterious effect in high-fat-dietinduced 

diabetes. 

-Transcriptional and metabolic adaptations of noninnervated 

cultured primary human myotubes compared to 

human skeletal muscle. 

Publications* 


Activation of peroxisome proliferator-activated receptor- 

{delta} by GW501516 prevents fatty acid-induced nuclear 

factor-{kappa}B activation and insulin resistance in skeletal 

muscle cells 

Coll T, Alvarez-Guardia D, Barroso E, Gómez-Foix AM, 

Palomer X, Laguna JC, Vázquez-Carrera M 


IF: 4.752 first quartile. With other CIBERDEM groups: 

M Vázquez Carrera 



40 CibeRdem

Comparative gene expression profiling between human 

cultured myotubes and skeletal muscle tissue 

Raymond F, Métairon S, Kussmann M, Colomer J, 

Nascimento A, Mormeneo E, García-Martínez C, Gómez- 

Foix AM 

BMC Genomics, 11, 125 (2010) 

IF: 3.759 first quartile. With other international groups 

Expression of glycogen phosphorylase isoforms in cultured 

muscle from patients with McArdle’s disease carrying the 

p.R771PfsX33 PYGM mutation 

Nogales-Gadea G, Mormeneo E, García-Consuegra I, 

Rubio JC, Orozco A, Arenas J, Martín MA, Lucia A, Gómez- 

Foix AM, Martí R, Andreu AL 

PLoS One, 5, e13164 (2010) 

IF: 4.351 first decile. With other CIBERs: CIBERER 



Estudio de los mecanismos de disfuncionalidad del 

proceso metabólico del glucógeno asociados a la atrofia 

en células de músculo esquelético humano 


2010-2012 

Principal Investigator: Anna Maria Gómez Foix 

Autonomous Community projects 

Acreditació de Grup de Recerca de Catalunya 

Generalitat de Catalunya, 2009 SGR 10: 2009-2013 


Desenvolupament d’un dispositiu d’electroporació a 

plaques estàndard multipouet 

Centro de Innovación y Desarrollo Empresarial (CIDEM), 

Generalitat de Catalunya, VALTEC09-1-00061: 2009-2011 


Coordinator: Ramon Bragós 

Ajut per la contractació de personal de suport a la recerca 

Generalitat de Catalunya, SGR00932: 2007-2010 


Coordinators: AM Gómez Foix, A Boronat 







CIBERDEM groups: AM Gómez Foix, J Vendrell, A Zorzano, 

J Balsinde, S Fernández Veledo, E Montanya, R Simó, M 

Vázquez Carrera ■ 

Effect of PGC-1α-overexpression in myotube lipid droplets. Cells 

were transduced with Ad-GFP or Ad-PGC-1α adenovirus and incubated 

with 0.5 mM oleate for 16 h to induce triglyceride accumulation. 

Cells were fixed and then treated with the lipophilic stain 

Nile Red. Representative lipid droplet micrographs from confocal 

microscopy are shown. White bars represent 5 µm. 


41

Metabolic engineering and diabetes therapy 

Institut de Recerca Biomèdica, Barcelona 

www.irbbarcelona.org 

Principal Investigator Joan J Guinovart guinovart@irbbarcelona.org Associate researchers Joaquim Calbó, María del Mar García Postdoctoral 

fellows Adelaida Díaz, Jordi Duran, Carlos Rodríguez, Delia Zafra Research assistant Anna Adrover PhD students Óscar Blanco, Carles 

Martínez, Laura Nocito, Isabel Sáez, Jordi Vallès Lab technicians Emma Veza, Ester Guerra Administrative staff Carolina Sánchez 






Private funds: 2 


Awards: 2 

Keywords 

Carbohydrate metabolism. Insulin sensitivity and 

resistance. Metabolic syndrome. Oral pharmacological 

agents. Retinopathy. 


-Mechanisms of control of glucose storage in the liver and 

muscle and their alterations in diabetes mellitus. 

-The consequences of altered glycogen deposition 

in various tissues in diabetes mellitus and in several 

neurodegenerative diseases. 

-The identification of potential molecular targets that 

regulate glycogen metabolism and the characterization of 

novel compounds with anti-diabetic action. 

Publications* 


Hepatic overexpression of a constitutively active form of 

liver glycogen synthase improves glucose homeostasis 

Ros S, Zafra D, Valles-Ortega J, García-Rocha M, Forrow S, 

Domínguez J, Calbó J, Guinovart JJ 

J Biol Chem, 285, 37170-37177 (2010) 




Estudio de un nuevo mecanismo de regulación del 

metabolismo del glucógeno. Análisis de las implicaciones 

patológicas de la acumulación anómala de polímeros de 

glucosa 

Ministerio de Ciencia e Innovación, BFU2008-00769: 

2009-2011 

Principal Investigator: Joan J Guinovart 


Ayudas de apoyo a grupos de investigación 

Generalitat de Catalunya (AGAUR), SGR2009-1176: 

2009-2013 




42 CibeRdem

Private funds 

Mejora de la predicción traslacional de los ensayos de 

seguridad no clínica al hombre 

CDTI-Noscira (formerly Neuropharma), MELLIUS (CENIT): 

2007-2010 


A study of the action mechanism of glycogen synthase 

activators 

Hoffmann-La Roche: 2010 




and their involvement in the ethiogenesis of diabetes mellitus 

GIDIPRED: 2009-2010 

Coordinator: Joan J Guinovart 

CIBERDEM groups: JJ Guinovart, R Gomis, R Simó 

Restoration of hepatic glycogen deposition reduces hyperglycaemia 

and hyperphagia in STZ-diabetic rats. Hepatic glycogen 

deposition was restored by targeted expression of an active liver 

glycogen synthase (active LGS). a) Blood glucose (mg/dl) was 

measured daily for 144 hours after adenoviral injection by using 

tail vein blood samples. b) Food intake was measured during three 

successive 24-h periods, beginning 3 days after viral treatment. 

Data represent mean intake/24 h ± S.E. 




Coordinator: Ramon Gomis 

CIBERDEM groups: JJ Guinovart, X Correig, R Gomis 

Awards 

Miembro numerario de la Reial Acadèmia de Farmàcia de 

Catalunya (2010) 

Institution: Reial Acadèmia de Farmàcia de Catalunya 

Awardee: Joan J Guinovart 

Miembro del Institut d’Estudis Catalans (2010) 

Institution: Institut d’Estudis Catalans 

Awardee: Joan J Guinovart ■ 

In the search for potential modulators of glycogen synthase, we 

have determined the crystallographic structure of monomeric 

PaGS. The enzyme is represented by coloured surfaces (carbon 

atoms in grey, nitrogen atoms in blue and oxygen atoms in red) 

while the bound maltotetraose molecule is represented by sticks, 

including its electron density. CBD, Carbohydrate Binding Domain. 


43

Molecular mechanisms of insulin resistance and 

sensitivity in peripheral tissues 

Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Madrid 

www.iib.uam.es 

Principal Investigator Ángela Martínez Valverde avalverde@iib.uam.es Postdoctoral fellows Águeda González, Jesús Revuelta, Beatriz 

Santamaría PhD students Virginia Pardo, Maysa Mobasher Lab technician Soledad Miranda 


Publications: 4, 1 of them in the first decile, 2 in the first quartile 

and 1 in the second quartile 







Keywords 

Cytokines. Hormone receptors. Insulin action. Insulin sensitivity 

and resistance. Retinopathy. Weight regulation and obesity. 


-The inhibition of PTP1B by genetic and pharmacological 

approaches in systemic IRS-2-deficient mice as a molecular 

strategy to restore IRS-1-mediated insulin signalling and 

hepatic insulin sensitization. 

-The study of the critical nodes of the insulin-signalling 

cascade in human biopsies from patients with non-alcoholic 

hepatic steatosis (NAFLD), steatohepatitis (NASH) and 

hepatitis virus C infection (HCV). 

-The effects of insulin sensitization by PTP1B deficiency on 

hepatic regeneration in mice fed on chow or a high fat diet: 

molecular mechanisms involved. 

-The effects of PTP1B deficiency on age-induced insulin 

resistance and metabolic damage. 

-The effect of PTP1B deficiency on postnatal liver growth: 

alterations in the GH/IGF-1 system. 

-The possible beneficial effect of PTP1B inhibition in the 

impairment of survival of photoreceptor cells in IRS-2- 

deficient mice. 

-Stress and survival signalling pathways in diabetic retinopathy. 

Publications* 


Beneficial effects of PTP1B deficiency on brown adipocyte 



44 CibeRdem

differentiation and protection against apoptosis induced by 

pro- and anti-inflammatory stimuli 

Miranda S, González-Rodríguez A, Revuelta-Cervantes J, 

Rondinone CM, Valverde AM 

Cell Signal, 22, 645-659 (2010) 

IF: 4.094 second quartile. With other international groups 

Inhibition of PTP1B restores IRS1-mediated hepatic insulin 

signaling in IRS2-deficient mice 

González-Rodríguez A, Mas Gutierrez JA, Sanz-González 

S, Ros M, Burks DJ, Valverde AM 


IF: 8.505 first decile. With other CIBERDEM groups: D Burks 


The identification of neurodegenerative mechanisms that 


of insulin signalling and apoptosis 

NEURONET-DIAB: 2009-2010 

Coordinator: Deborah Burks 

CIBERDEM groups: A Martínez Valverde, D Burks, R Simó ■ 

Normal proliferation and tumorigenesis but impaired 

pancreatic function in mice lacking the cell cycle 

regulator sei1 

Fernandez-Marcos PJ, Pantoja C, Gonzalez-Rodriguez A, 

Martin N, Flores JM, Valverde AM, Hara E, Serrano M 



PTP1B deficiency enhances liver growth during suckling 

by increasing the expression of insulin-like growth 

factor-I 

Escrivá F, González-Rodriguez A, Fernández-Millán E, 

Rondinone CM, Alvarez C, Valverde AM 

J Cell Physiol, 225, 214-222 (2010) 

IF: 4.586 first quartile. With other international groups. With 

other CIBERDEM groups: C Álvarez 



Hormonal regulation of adipocyte cell death: applications 

in the design of anti-obesity therapies 

Ministerio de Ciencia e Innovación, PROFIT2007-0501: 


Principal Investigator: Ángela Martínez Valverde 

Associate investigators: Soledad Miranda, Águeda 

González, Jesús Revuelta 

Estudio de la sensibilidad hepática a la insulina por la 

inhibición de la proteína tirosina fosfatasa 1B 

Ministerio de Ciencia e Innovación, SAF2009-08114: 



Associate investigators: Águeda González, Jesús Revuelta, 

Beatriz Santamaría, Maysa Mobasher, Virginia Pardo 

Private funds 

The role of PTP1B in hepatocyte apoptosis 

Hoffmann-La Roche: 2009-2011 


Associate investigators: Águeda González, Maysa 

Mobasher, Cristina Rondinone 

PTP1B deficiency protects against resveratrol-induced Foxo1 nuclear 

accumulation in brown adipocytes: (upper panel) Nuclear 

protein (50 µg) was submitted to Western blot analysis with the 

anti-Foxo1 antibody. Nucleolin was used as a loading control. A 

representative experiment is shown. (lower panel) Immunofluorescence 

of Foxo1 in control and brown adipocytes treated with 100 

µM resveratrol for 16 h. Representative images are shown. 


45

Molecular characteristics, and action of incretins, 

in the physiopathology of glucose, lipids and 

bone metabolism 

Fundación Jiménez Díaz, Madrid 

www.fjd.es 

Principal Investigator María Luisa Villanueva Peñacarrillo mlvillanueva@fjd.es Associate researchers Nieves González, Isabel Valverde, 

Alicia Acitores, Bernardo Nuche Berenguer Predoctoral students Irene Gutiérrez, Paola Moreno, Irene Ramos 





PhD theses: 1 

Awards: 1 

Keywords 

Glucose transport. Hormone receptors. Incretins. Insulin 

sensitivity and resistance. Lipid metabolism. 


-The effects and mechanisms in the action of GLP-1 action 

(glucagon-like-peptide 1) -an incretin with antidiabetic 

properties - and also that of GLP-1-homologue peptides, 

on glucose, lipids and bone metabolism. 

-The mechanism of insulin secretion. 

-The genetic characteristics, pharmacology and function 

of the human BRS-3 receptor, a possible target for the 

treatment of diabetes and obesity. 

-The effect of amylin on glucose metabolism. 



The genetic characteristics, pharmacology and function 

of the human BRS-3 receptor, a possible target for the 

treatment of diabetes and obesity 

Instituto de Salud Carlos III (ISCIII), FIS CP08/00158: 2009- 

2011 

Principal Investigator: Nieves González Gómez 

A molecular characterization of GLP-1 receptor in 

extrapancreatic tissues 

Instituto de Salud Carlos III (ISCIII), PS09/01185: 2010- 

2012 

Principal Investigator: Nieves González Gómez 

Associate investigators: ML Villanueva Peñacarrillo, Irene 

Ramos Álvarez, Irene Gutiérrez Rojas 

46 CibeRdem

Private funds 

The role of Amylin in the endothelial dysfunction asociated 

with type 2 diabetes. An experimental model 

Fundación Mutua Madrileña, AP/65232009: 2009-2010 

Principal Investigator: ML Villanueva Peñacarrillo 

Coordinator: Leocadio Rodríguez Mañas 


Mechanisms of endothelial dysfunction in diabetes: the role 

of amylin and circulating endothelial cells 

ENDODIAB: 2009-2010 

Coordinator: Anna Novials 

CIBERDEM groups: ML Villanueva Peñacarrillo, R Gomis, 

A Novials 

PhD theses 

Alterations in the glucose metabolism in insulin-resistant 

and type 2 diabetic states: Normalizing actions of GLP-1 

and Exendin-4 

Author: Paola Moreno Pérez 

Thesis advisor: ML Villanueva Peñacarrillo 

University: Universidad Autónoma de Madrid 

Thesis defense date: December 17, 2010 

Awards 

Premio a la Investigación (2010) 

Institution: Fundación Jiménez Díaz 

Awardee: Bernardo Nuche Berenguer ■ 

Potentiating effect of amylin treatment on insulin-induced glucose 

transport in isolated adipocytes from normal, insulin-resistant (IR) 

and type 2 diabetic (T2D) rats, saline treated (control) and treated 

with amylin ( ). All results (mean±SEM) are expressed as a 

percentage increment of the value obtained in cells from normal 

control rats, incubated in the absence (basal) or presence of 10 -9 

Minsulin ( ). *p

Heterogenic and polygenic diseases. Genexartis 

Institut de Recerca Biomèdica, Barcelona 

www.irbbarcelona.org 

Principal Investigator Antonio Zorzano antonio.zorzano@irbbarcelona.org Associate researchers Marta Camps, Anna Gumà, Manuela 

Sánchez Feutrie, Xavier Testar Postdoctoral fellows Maria Àngels Díaz, Saska Ivanova, Iliana López, Deborah Naon, Montserrat Romero, 

David Sebastián, Eleonore Sorianello Research assistant Juan Carlos Monasterio PhD students Víctor Francis, María Isabel Hernández, 

Vicente Martínez, Caroline Mauvezin, Sónia Pereira, David Sala, Ana Sancho Lab manager Olga Bausà Technologist Jessica Segalés 







European projects: 3 




PhD theses: 1 

Keywords 

Genomics. Insulin action. Insulin sensitivity and resistance. 

Carbohydrate metabolism. Lipid metabolism. Protein 

metabolism. Oral pharmacological agents. Stem cells. 

Transcription factors. Exercise. 


Molecular mechanisms involved in the development of 

insulin resistance and the identification of novel targets for 

diabetes therapy: 

a) analysis of the role of mitochondrial dynamics proteins in 

metabolic homeostasis, in the control of insulin signalling, 

and in the response to cell stress, 

b) a study of the role of DOR protein in insulin resistant 

states, 

c) analysis of the physiological role of neuregulins in skeletal 

muscle. 

Publications* 


dDOR is an EcR coactivator that forms a feed-forward loop 

connecting insulin and ecdysone signalling 

Francis VA, Zorzano A, Teleman AA 

Curr Biol, 20, 1799-1808 (2010) 

IF: 10.992 first decile. With other international groups 

PP2A regulatory subunit PP2A-B’ counteracts S6K 

phosphorylation 

Hahn K, Miranda M, Francis VA, Vendrell J, Zorzano A, 

Teleman AA 

Cell Metab, 11, 438-444 (2010) 

IF: 17.350 first decile. With other international groups. With 

other CIBERDEM groups: J Vendrell 



48 CibeRdem

Subjects with early-onset type 2 diabetes show defective 

activation of the skeletal muscle PGC-1{alpha}/Mitofusin-2 

regulatory pathway in response to physical activity 

Hernández-Alvarez MI, Thabit H, Burns N, Shah S, Brema 

I, Hatunic M, Finucane F, Liesa M, Chiellini C, Naon D, 

Zorzano A, Nolan JJ 

Diabetes Care, 33, 645-651 (2010) 


Am J Physiol Endocrinol Metab, 298, E742-750 (2010) 


Mitochondrial fusion proteins: dual regulators of morphology 

and metabolism 

Zorzano A, Liesa M, Sebastián D, Segalés J, Palacín M 

Semin Cell Dev Biol, 21, 566-574 (2010) 


The nuclear cofactor DOR regulates autophagy in 

mammalian and Drosophila cells 

Mauvezin C, Orpinell M, Francis VA, Mansilla F, 

Duran J, Ribas V, Palacín M, Boya P, Teleman AA, 

Zorzano A 

EMBO Rep, 11, 37-44 (2010) 


Reviews 

Alterations in the mitochondrial regulatory pathways 

constituted by the nuclear co-factors PGC-1alpha or PGC- 

1beta and mitofusin 2 in skeletal muscle in type 2 diabetes 

Zorzano A, Hernández-Alvarez MI, Palacín M, Mingrone G 

Biochim Biophys Acta, 1797, 1028-1033 (2010) 


Emerging role of neuregulin as a modulator of muscle 

metabolism 

Gumà A, Martínez-Redondo V, López-Soldado I, Cantó C, 

Zorzano A 


European projects 

Transnational cooperation for technological innovation in 

the development of molecules for the treatment of obesity 

and diabetes 

SUDOE (European Community Initiative INTERREG IV for 

Southwestern Europe), SOE1/P1/E178: 2009-2012 

Principal Investigator: A Zorzano 

Integration of the system models of mitochondrial function 

and insulin signalling and its application in the study of 

complex diseases 

European Union, Seventh Framework Programme (FP7), 

HEALTH-F4-2008-223450: 2008-2011 

Principal Investigator: A Zorzano 

Adipose tissue: a key target for prevention of the metabolic 

syndrome 

European Science Foundation, COST Action BM0602: 

2007-2011 

Morphology of the endoplasmic reticulum in wild type and Mfn2 knockout mouse embryo fibroblasts. Cells were transfected with sec61b- 

GFP and thereafter were treated with thapsigargin (1µM) to inhibit SERCA activity. Images show labelling of the endoplasmic reticulum. 


49

Principal Investigator: Antonio Zorzano 

Coordinator: Jürgen Eckel 


Genetic determinants of the metabolic alterations in obesity 

and/or type 2 diabetes and their participation in insulin 

resistance 


2009-2013 


Caracterización de los efectos de las neuregulinas en 

modelos de resistencia a la insulina 


2009-2011 


Coordinator: Anna Gumà 


Molecular basis of metabolic disorders 

Departament d’Innovació, Universitats i Empresa, 

Generalitat de Catalunya, 2009SGR915: 2009-2013 








CIBERDEM groups: A Zorzano, J Vendrell, S Fernández 

Veledo, J Balsinde, AM Gómez Foix, E Montanya, R Simó, 


PhD theses 

Diabetes and obesity regulated gene (DOR): dual role in 

Drosophila and in mammalian cells 

Author: Victor Francis Hoste 

Thesis advisor: Antonio Zorzano 

University: Universitat de Barcelona 

Thesis defense date: July 6, 2010 ■ 

50 CibeRdem

Area 2 

Dyslipidaemia, metabolic syndrome 

and microvascular complications of diabetes 










Clinical trials: 27 

Clinical practice guidelines: 3 

Patents: 1 

Spin-offs: 1 

PhD theses: 9

The research activity of this area is focused on the study of dyslipidaemias, metabolic syndrome and diabetic microvascular 

complications. The area comprises a total of 11 research groups and includes both basic and clinical researchers. The 

aim is to generate traslational collaborative research, ranging from epidemiological studies, and a global therapeutic 

approach to diabetes and its complications, reaching into the area of genetic studies and the search for new biomarkers 

of cardiovascular risk in diabetic subjects. 

During the year 2010, the groups included in Area 2 published a total of 59 scientific papers; 22 of them were published 

in journals in the first decile of the speciality. The accumulated Impact Factor (IF) for this period was 268.13. It is important 

to emphasize that 9 papers were the result of collaborations between CIBERDEM research groups, and an additional 21 

papers were the result of working collaborations with other groups included in different CIBER programmes. Furthermore, 

groups from Area 2 were successful in obtaining 60 competitive research grants to fund their respective research projects. 

Thirty of these were grants awarded jointly to different CIBERDEM groups. 

In relation to other scientific activities in Area 2 during 2010, a total of 27 clinical research trials were conducted and 9 

doctoral theses supervised by investigators in the Area were defended. Finally, the results of research activities were 

transferred to clinical practice, with 3 new clinical guidelines being published, but there were also other important 

outcomes, such as the registration of a patent and the generation of a spin-off. 

Rafael Carmena 



53

The Eicosanoid Research Division 

Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Valladolid 

www.balsinde.org 

Principal Investigator Jesús Balsinde jbalsinde@ibgm.uva.es Associate researchers María Ángeles Balboa, Olimpio Montero 

Postdoctoral fellows Clara Meana, Julio Rubio PhD students Alma Astudillo, Esperanza Esquinas, Luis Gil de Gómez, Lucía Peña, Martín 

Valdearcos Lab managers Montserrat Duque, Yolanda Sáez Lab technician David Balgoma 


Publications: 4, 3 of them in the first quartile and 1 in the second 

quartile 





Keywords 

Cytokines. Lipid metabolism. Lipid signalling. Metabolic 

syndrome. Phospholipases. 


-Lipid metabolic pathways in obesity and inflammation. 

-The molecular and cell biology of lipid droplets. 

-Lipidomics and metabolipidomics: characterization of 

cellular lipidomes and lipid pathways by mass spectrometry. 

-Cellular utilization of free fatty acids: acylation and 

transacylation mechanisms. 

Publications* 


Markers of monocyte activation revealed by lipidomic 

profiling of arachidonic acid-containing phospholipids 

Balgoma D, Astudillo AM, Pérez-Chacón G, Montero O, 

Balboa MA, Balsinde J 

J Immunol, 184, 3857-3865 (2010) 


Signaling role for lysophosphatidylcholine acyltransferase 

3 in receptor-regulated arachidonic acid reacylation 

reactions in human monocytes 

Pérez-Chacón G, Astudillo AM, Ruipérez V, Balboa MA, Balsinde J 





54 CibeRdem

The cationic cluster of group IVA phospholipase A2 

(Lys488/Lys541/Lys543/Lys544) is involved in translocation 

of the enzyme to phagosomes in human macrophages 

Casas J, Valdearcos M, Pindado J, Balsinde J, Balboa MA 

J Lipid Res, 51, 388-399 (2010) 




CIBERDEM groups: J Balsinde, J Vendrell, A Zorzano, S 

Fernández Veledo, AM Gómez Foix, E Montanya, R Simó, 

M Vázquez Carrera ■ 

Review 

Lipidomic approaches to the study of phospholipase 

A2-regulated phospholipid fatty acid incorporation and 

remodelling 

Balgoma D, Montero O, Balboa MA, Balsinde J 

Biochimie, 92, 645-650 (2010) 

IF: 3.897 second quartile 



A lipidomics approach to the study of the innate immune 

response: mechanisms governing arachidonic acid 

availability and metabolism in macrophages 



Principal Investigator: J Balsinde 

Associate investigator: O Montero 

Inflammation and obesity, two processes regulated by the 

same enzyme: the magnesium-dependent phosphatidic 

acid phosphatase 



Principal Investigator: MA Balboa 

Mass spectrometry analysis of arachidonic acid-containing glycerophospholipids 

in human macrophages. The cells were transfected 

with siRNA negative control (open bars) or siRNA against 

lipin-1 (grey bars) for 48 h. Afterwards the analysis of arachidonic 

acid-containing phospholipids was carried out by liquid chromatography/mass 

spectrometry. 


The role of calcium-independent phospholipase A2 in 

oxidative stress 

Junta de Castilla y León, CSI09A08: 2008-2010 


Associate investigator: MA Balboa 

The regulation of inflammation by lipin, an enzyme involved 

in obesity 

Junta de Castilla y León, BIO39/VA04/10: 2010-2011 

Principal Investigator: MA Balboa 

Biochemical signalling mechanisms associated with innate 

immunity receptors in myeloid cells 

Junta de Castilla y León, GR230: 2009-2010 


Coordinator: M Sánchez 

Associate investigator: MA Balboa 





Lipin1β localization in human macrophages. The cells were transfected 

with lipin1β-EGFP (green), and stained with DAPI (nuclei, 

blue) and Nile Red (cytoplasmic lipid bodies, red). The picture 

shows a lipin1β-transfected macrophage that has phagocytosed 

a non-transfected cell. 


55

Metabolic disease and cardiovascular risk 

Hospital de la Santa Creu i Sant Pau, Servei de Bioquímica i Endocrinologia, Barcelona 

www.santpau.cat 

Principal Investigator Francisco Blanco Vaca fblancova@santpau.cat Associate researchers Joan Carles Escolà, Jesús María Martín, 

Antonio Pérez, Josep Julve Postdoctoral fellows Gemma Llaverias, Juan Antonio Sánchez Lab technicians Carme Mayoral, Cristina 

Muñoz, Rosa Roig, David Santos 












Keywords 

Genetics type 2 diabetes. Lipid metabolism. Lipids, 

lipoproteins. Metabolic syndrome. Pathogenic mechanisms. 


-Antiinflammatory actions of HDL: effects on diabetes 

mellitus and atherothrombotic cardiovascular disease. 

-Genetics of complex metabolic diseases: hyperlipidaemia, 

type 2 diabetes and hyperhomocysteinaemia. 

-Development of experimental-biochemistry and molecularbiology 

techniques and their application to clinical 

laboratory practice (innovation). 

Publications* 


Cyclooxygenase 2 inhibition exacerbates palmitate-induced 

inflammation and insulin resistance in skeletal muscle cells 

Coll T, Palomer X, Blanco-Vaca F, Escolà-Gil JC, Sánchez 

RM, Laguna JC, Vázquez-Carrera M 




Disodium ascorbyl phytostanol phosphate (FM-VP4), a 

modified phytostanol, is a highly active hypocholesterolaemic 



56 CibeRdem

agent that affects the enterohepatic circulation of both 

cholesterol and bile acids in mice 

Méndez-González J, Süren-Castillo S, Calpe-Berdiel L, 

Rotllan N, Vázquez-Carrera M, Escolà-Gil JC, Blanco-Vaca F 

Br J Nutr, 103, 153-160 (2010) 



Human apolipoprotein A-II determines plasma triglycerides 

by regulating lipoprotein lipase activity and high-density 

lipoprotein proteome 

Julve J, Escolà-Gil JC, Rotllan N, Fiévet C, Vallez E, de la 

Torre C, Ribas V, Sloan JH, Blanco-Vaca F 

Arterioscler Thromb Vasc Biol, 30, 232-238 (2010) 


Books 

Cliniguía - Actualización de diagnóstico y terapéutica, 

EviScience (2010) 

Authors: Muñoz Calvo B, Sampol Rubio G, García Diéz JD, 

Pérez Pérez A, Fdez Fresnedo, Sarria Cepeda C, Escamilla 

Crespo C 

Hiperglucemia en el paciente hospitalizado: Diálogo entre 

expertos, Edika Med, Barcelona (2010) 

Author: Pérez A (coordinator) 

Tratamiento fisiopatológico de la diabetes mellitus tipo 2: 

papel de la vildagliptina, Profármaco.2, Barcelona (2010) 

Author: Pérez A (coordinator) 

Book chapters 

Book: Biochemical Aspects of Human Nutrition (Avigliano L, 

Rossi KL, ed), Transworld Research Network, India, Kerala (2010) 

Chapter: Plant sterols, cholesterol metabolism and related 

disorders 

Authors: Calpe-Berdiel L, Méndez-González J, Llaverias G, 

Escolà-Gil JC, Blanco-Vaca F 

Pages: 223-242 

Book: Formación en Hipertrigliceridemias. JF Ascaso (ed), 

Equalmás 5 SL (2010) 

Chapter: Hipertrigliceridemias. Concepto y valores de corte 

Authors: Masana L, Pérez A 

Pages: 17-34 


European project 

HDL: from biological understanding to clinical exploitation 

COST Actions, European Union, BM0904: 2010-2014 

Principal Investigator: Kardassis D 

Associate investigators: Blanco Vaca F, Gómez-Coronado 

D, Chroni A, Jauhiainen M, Savolainen M, von Eckardstein 

A, Kontsush A, Staels B, Shunkert H, Nofer JR, Calabresi L, 

Bernini F, Kuivenhoven JA, Karlsson H 


Papel de las lipasas que intervienen en el metabolismo 

lipoproteico en la modulación de las propiedades 

antiaterogénicas de las HDL (transporte reverso de 

colesterol específico de macrófagos y capacidad 

antioxidante) 

Instituto de Salud Carlos III, PI08/1147: 2009-2011 

Principal Investigator: Blanco Vaca F 

Associate investigators: Llaverias G, Roig R 

Efectos sistémicos del síndrome de las apneas durante el 

sueño. Análisis mediante modelos animales y estudios en 

humanos 


Principal Investigator: Mayos M 

Associate investigator: Pérez A 

Efecto de la expresión de la nicotinamida n-metiltransferasa 

en la concentración plasmática de homocisteína y su 

relación con la aterogénesis en modelos animales 

Instituto de Salud Carlos III, PI07/1067: 2008-2010 

Principal Investigator: Julve J 

Associate investigators: Calpe Berdiel L, Jorba O, Martínez S, 

Méndez J 

Análisis funcional de las propiedades antiaterogénicas de 

las HDL (transporte reverso de colesterol específico de 

macrófagos in vivo y capacidad antioxidante) en modelos 

animales de diabetes mellitus y arteriosclerosis 

Instituto de Salud Carlos III, PI09/00178: 2010-2012 

Principal Investigator: Escolà Gil JC 

Associate investigators: Roig R, Santos D, Méndez J 


Grup de recerca d’estructura de lipoproteïnes, dislipèmies 

i altres factors de risc cardiovascular 

AGAUR, Generalitat de Catalunya, 2009SGR1205: 2009-2014 

Principal Investigator: Ordóñez Llanos J 

Associate investigators: Blanco Vaca F, Julve J, Escolà Gil 

JC, Benítez S, Sánchez Quesada JL 

Private funds 

Propiedades antiaterogénicas de las HDL en presencia 

de hiperhomocisteinemia: análisis y búsqueda de 

biomarcadores mediante técnicas proteómicas 

Fundación Española de Arteriosclerosis, Beca SEA/FEA 

Almirall: 2010-2011 

Principal Investigator: Blanco Vaca F 

Associate investigator: Julve J 

Efecto de la apolipoproteína A-II sobre el metabolismo 

de los triglicéridos en ratones transgénicos y en sujetos 

normolipémicos 

Fundación Española de Arteriosclerosis, Beca FEA/SEA de 

Investigación Básica: 2008-2010 


57

Principal Investigator: Escolà Gil JC 

Associate investigators: Blanco Vaca F, Julve J 


Characterization of low HDL syndrome in type 2 diabetes 



CIBERDEM groups: F Blanco Vaca, R Carmena, X Correig, 


Cooperative population and database studies for genetic 

association analysis in T2DM and related traits 

INGENFRED: 2009-2010 

Coordinator: Felipe Javier Chaves 

CIBERDEM groups: F Blanco Vaca, R Carmena, M Serrano 

Ríos, F Soriguer 

CIBERDEM Biobank 

Coordinator: A Novials 

CIBERDEM Biobank Nodes: F Blanco Vaca, R Gomis, A 

Novials, J Vendrell, L Masana, L Castaño, M Serrano Ríos, 

F Soriguer, R Carmena 

Clinical trials 

INSPIRE ME/IAA. International Study of Intra-abdominal 

Adiposity and its Relationships with Cardiometabolic Risk/ 

Intra-abdominal Adiposity. Phase IV 

Sanofi-Aventis: 2007-2010 

Researcher: Antonio Pérez 

HOSMIDIA. Manejo de la diabetes mellitus tipo 2 durante 

la hospitalización: eficacia y factibilidad de las pautas 

fisiológicas de insulinoterapia. Phase IV 


Coordinator: Antonio Pérez 

HINTHER. Manejo de la hiperglucemia en los hospitales: 

eficacia de las pautas administradas de insulina más 

fisiológicas. Phase IV 


Coordinator: Antonio Pérez ■ 

HDL inhibits LDL oxidative modification and inflammation. 

58 CibeRdem

Dyslipidaemia, inflammation and endothelial 

dysfunction 

Servicio de Endocrinología y Nutrición, Fundación Investigación Hospital Clínico Universitario de Valencia 

www.fihcuv.es 

Principal Investigator Rafael Carmena rafael.carmena@uv.es Associate researchers Juan Francisco Ascaso, Miguel Catalá, Felipe Javier 

Chaves, Sergio Martínez Hervás, José Tomás Real Postdoctoral fellows Ana Bárbara García, Marta Peiró Lab manager Sebastián Blesa 

Lab technicians Esther Benito, Clara María Bixquert, Nieves Brito, Griselda de Marco 










PhD theses: 1 

Keywords 

Insulin sensitivity and resistance. Lipid metabolism. 

Macrovascular disease. Metabolic syndrome. Weight 

regulation and obesity. 


The degree of arterial damage and age of onset of 

arteriosclerosis varies in patients with primary dyslipidaemias 

or diabetes, indicating the existence of other contributing 

factors. We have investigated the role of oxidative stress 

(OS), inflammation, insulin resistance, and prediabetic states 

as possible candidates. 

Our research lines include: primary hyperlipidaemias 

- genetic diagnosis and cardiovascular risk; primary 

mixed hyperlipidaemias - insulin resistance and diabetes 

mellitus; postprandial lipidaemia and arteriosclerosis in 

insulin-resistant states; insulin resistance, inflammation 

and oxidative stress; diabetic foot - diagnosis, prevention 

and treatment; and genetic factors regulating BMI and 

abdominal obesity. 

Publications* 


Association of selected ABC gene family single nucleotide 

polymorphisms with postprandial lipoproteins: results from 




59

the population-based Hortega study 

Abellán R, Mansego ML, Martínez-Hervás S, Martín- 

Escudero JC, Carmena R, Real JT, Redon J, Castrodeza- 

Sanz JJ, Chaves FJ 

Atherosclerosis, 211, 203-209 (2010) 

IF: 4.522 first decile. With other CIBERs: CIBEROBN 

Circulating mononuclear cells nuclear factor-kappa 

B activity, plasma xanthine oxidase, and low grade 

inflammatory markers in adult patients with familial 

hypercholesterolaemia 

Real JT, Martínez-Hervás S, García-García AB, Civera M, 

Pallardó FV, Ascaso JF, Viña JR, Chaves FJ, Carmena R 

Eur J Clin Invest, 40, 89-94 (2010) 

IF: 2.643 first quartile. With other CIBERs: CIBERER 

FABP4 plasma levels are increased in familial combined 

hyperlipidemia 

Cabré A, Lázaro I, Cofán M, Jarauta E, Plana N, Garcia-Otín 

AL, Ascaso JF, Ferré R, Civeira F, Ros E, Masana L 



L Masana. With other CIBERs: CIBEROBN 

How ineffective hypertension control in subjects treated 

with angiotensin-converting enzyme inhibitors is related to 

polymorphisms in the renin-angiotensin-aldosterone system 

Morales-Suárez-Varela MM, Mansego ML, Martín-Escudero 

JC, Llopis-González A, Chaves FJ, López-Izquierdo R, 

Frutos-Llanes R, Vicedo-Cabrera AM 

Eur J Pharm Sci, 39, 380-386 (2010) 

IF: 2.608 second quartile. With other CIBERs: CIBERESP, 

CIBEROBN 

Plasma homocysteine levels are associated with ulceration 

of the foot in patients with type 2 diabetes mellitus 

González R, Pedro T, Real JT, Martínez-Hervás S, Abellán 

MR, Lorente R, Priego A, Catalá M, Chaves FJ, Ascaso JF, 

Carmena R 

Diabetes Metab Res Rev, 26, 115-120 (2010) 


Book chapter 

Book: Endocrinología, Editorial Panamericana, Madrid (2010) 

Chapter: Dislipemias. Metabolismo lipídico. 

Authors: Ascaso JF, Martínez-Hervás S 

Pages: 1075-1086 



CAIBER de Unidades Centrales de Investigación Clínica y 

en Ensayos Clínicos 

Instituto de Salud Carlos III, CAI08/01/0039: 2010 

Principal Investigator: Andrés Cervantes 

Associate investigator: Rafael Carmena 

Scanning microarrays. 

60 CibeRdem

Daño orgánico en la diabetes mellitus tipo 2 y prediabetes: 

factores de riesgo e influencia de los sistemas 

reninaangiotensina-aldosterona y óxido nítrico-estrés 

oxidativo 


Principal Investigator: Felipe Javier Chaves 


Regulación del IMC, de la circunferencia abdominal, del 

desarrollo de obesidad y de obesidad central 

Conselleria d’Educació, Generalitat Valenciana, 

PROMETEO/2009/029: 2010 

Principal Investigator: Rafael Carmena 





CIBERDEM groups: R Carmena, F Blanco Vaca, X Correig, 






CIBERDEM groups: R Carmena, F Blanco Vaca, M Serrano 

Ríos, F Soriguer 

Di@bet.es Study: 1st epidemiological study of the 

prevalence of type 2 diabetes in Spain 

Coordinator: F Soriguer 

CIBERDEM groups: R Carmena, F Soriguer, L Castaño, R 

Gomis, M Serrano Ríos, J Vendrell 



CIBERDEM Biobank Nodes: R Carmena, R Gomis, A 

Novials, J Vendrell, L Masana, L Castaño, M Serrano Ríos, 

F Soriguer, F Blanco Vaca 

PhD theses 

Elucidating the genetic susceptibility of hypertension 

associated microalbuminuria: genome wide scan study 

(GWAS) 

Author: Fernando Martínez García 

Thesis advisors: Josep Redón, Felipe Javier Chaves 

University: Universidad de Valencia 

Thesis defense date: 2010 ■ 


61

Diabetes, Obesity and Reproductive Endocrinology 

Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS and Universidad de Alcalá, 

Madrid 

www.hrc.es 

Principal Investigator Héctor F Escobar Morreale hescobarm.hrc@salud.madrid.org Associate researchers Francisco Álvarez Blasco, 

Susana Borruel Nacenta, María Rosa Insenser, Manuel Luque Ramírez, David Martí Sánchez, María Ángeles Martínez, Rafael Montes, 

José Luis San Millán PhD student Macarena Alpañés Lab manager Elena Fernández 


Publications: 5, 2 of them in the first decile and 3 in the second 

quartile 






Keywords 

Biomarkers and Imaging. Insulin sensitivity and resistance. 

Polycystic ovary syndrome. Proteomics. Metabolic surgery. 


The influence of the balance between androgens and 

oestrogens on the development of abdominal adiposity 

and visceral adipose tissue dysfunction in humans as 

pathogenetic factors of insulin resistance and diabetes, 

including: 

a) an integrated approach to the influence of sex 

hormones on the amount and dysfunction of visceral and 

subcutaneous fat as studied by clinical research, molecular 

genetics, molecular biology, genomics, proteomics and 

metabolomics. 

b) the identification of pathogenetic markers of diabetes in 

severe obesity and predictors of diabetes remission after 

bariatric surgery. 

Publications* 


Obesity impairs general health-related quality of life (HR- 

QoL) in premenopausal women to a greater extent than 

polycystic ovary syndrome (PCOS) 

Alvarez-Blasco F, Luque-Ramírez M, Escobar-Morreale HF 

Clin Endocrinol, 73, 595-601 (2010) 




62 CibeRdem

Proteomic analysis of plasma in the polycystic ovary 

syndrome identifies novel markers involved in iron 

metabolism, acute-phase response, and inflammation 

Insenser M, Martínez-García MA, Montes R, San-Millán JL, 

Escobar-Morreale HF 

J Clin Endocrinol Metab, 95, 3863-3870 (2010) 


The determinants of insulin sensitivity, β-cell function, 

and glucose tolerance are different in patients with 

polycystic ovary syndrome than in women who do not have 

hyperandrogenism 

Luque-Ramírez M, Alpañés M, Escobar-Morreale HF 

Fertil Steril, 94, 2214-2221 (2010) 


The role of genetic variation in peroxisome proliferatoractivated 

receptors in the polycystic ovary syndrome 

(PCOS): an original case-control study followed by 

systematic review and meta-analysis of existing evidence 

San-Millán JL, Escobar-Morreale HF 



frente a un anticonceptivo oral más un antiandrógeno 

(espironolactona). Phase II 

ENDOPCOS 02/2008: 2010-ongoing 

Name of the participants: HF Escobar Morreale (coordinator 

and researcher), M Alpañés Buesa and M Luque Ramírez 

(researchers) 


Assessment of cardiovascular risk and prevention of 

cardiovascular disease in women with the polycystic ovary 

syndrome: a position statement by the Androgen Excess & 

Polycystic Ovary Syndrome (AE-PCOS) Society 



Institution: Androgen Excess & Polycystic Ovary Syndrome 

(AE-PCOS) Society 

Authors: RA Wild, E Carmina, E Diamanti-Kandarakis, A 

Dokras, HF Escobar Morreale, W Futterweit, R Lobo, RJ 

Norman, E Talbott, DA Dumesic 

Treatment of polycystic ovary syndrome (PCOS) with 

metformin ameliorates insulin resistance in parallel with the 

decrease of serum interleukin-6 concentrations 

Luque-Ramírez M, Escobar-Morreale HF 

Horm Metab Res, 42, 815-820 (2010) 




Influencia de los andrógenos en el desarrollo de la 

adiposidad abdominal y de la disfunción metabólica 

del tejido adiposo visceral en humanos, como factores 

etiopatogénicos de la resistencia insulínica y la diabetes 

Instituto de Salud Carlos III, Fondo de Investigación 

Sanitaria, PI081147: 2009-2011 

Principal Investigator: Héctor F Escobar Morreale 



disorders, including diabetes, in severe obesity and their 

changes after bariatric surgery-induced weight loss 



CIBERDEM groups: HF Escobar Morreale, X Correig, E 

Montanya, R Simó, J Vendrell 


Protocolo de investigación sobre el perfil de riesgo 

cardiovascular asociado a mujeres con síndrome de 

ovario poliquístico o hiperandrogenismo ovulatorio, y 

evolución del mismo durante el tratamiento con metformina 

Representative Cy2-labelled internal standard proteome map indicating 

the proteins altered in PCOS. The four protein spots found 

significantly increased in the plasma samples from PCOS patients 

(P

Meta-analysis of the mean difference in fasting insulin levels among carriers of the PPAR-γ2 Pro12Ala variant compared with PPAR-γ2 

Reproduced from San-Mill‡ n & Escobar-Morreale. Clinical Endocrinology 72:383-392 

(2010), with permission from the Authors. 

Pro12Pro subjects considering PCOS patients and controls as a whole. CI, confidence interval; ID, identification; MD, mean difference. 

Image from: Clin Endocrinol, 2010 ■ 

64 CibeRdem

Prenatal growth restriction and subsequent risks 

for type 2 diabetes and cardiovascular disease 

Hospital Sant Joan de Déu, Universitat de Barcelona 

www.hsjdbcn.org 

Principal Investigator Lourdes Ibáñez libanez@hsjdbcn.org Associate researchers Paula Casano, María Victoria Marcos, Carme Valls 

Postdoctoral fellows Marta Díaz, David Sánchez Infantes Research assistant Cristina Duran PhD student Giorgia Sebastiani 


Publications: 5, 4 of them in the first decile and 1 in the first 

quartile 



International projects: 1 







Patents: 1 

Awards: 1 

Keywords 

Cytokines. Insulin sensitivity and resistance. Metabolic 

syndrome. Oral pharmacological agents. Paediatrics. 

Prevention of type 2 diabetes. 


-The influence of early nutrition on growth 

patterns, endocrine-metabolic profile and future 

cardiovascular risks in small-for-gestational-age 

(SGA) newborns. 

-The association of specific SNPs with catch-up growth 

characteristics, body composition and abdominal fat 

partitioning in SGA children. 

-The usefulness of insulin sensitizers as modifiers of 

pubertal onset and progression in SGA girls with excessive 

catch-up growth and advanced and rapidly progressive 

puberty. 

-The effects of low-dose combinations of insulin 

sensitizers and antiandrogens on cardiovascular risk 

parameters and body fat in adolescents with ovarian 

hyperandrogenism, hyperinsulinism, and cardiovascular 

risk factors. 

-The influence of genetic polymorphisms on the clinical 

response to insulin sensitization. 


65

Publications* 


A single nucleotide polymorphism in STK11 influences 

insulin sensitivity and metformin efficacy in hyperinsulinemic 

girls with androgen excess 

López-Bermejo A, Díaz M, Morán E, de Zegher F, Ibáñez L 



Carboxylation of osteocalcin affects its association with 

metabolic parameters in healthy children 

Prats-Puig A, Mas-Parareda M, Riera-Pérez E, González- 

Forcadell D, Mier C, Mallol-Guisset M, Díaz M, Bassols J, de 

Zegher F, Ibáñez L, López-Bermejo A 



Low body adiposity and high leptinemia in breast-fed 

infants born small-for-gestational-age 

Ibáñez L, Sebastiani G, Diaz M, Gómez-Roig MD, Lopez- 

Bermejo A, de Zegher F 

J Pediatr, 156, 145-147 (2010) 


Placental FTO expression relates to fetal growth 

Bassols J, Prats-Puig A, Vázquez-Ruíz M, García-González 

MM, Martínez-Pascual M, Avellí P, Martínez-Martínez R, 

Fàbrega R, Colomer-Virosta C, Soriano-Rodríguez P, Díaz 

M, de Zegher F, Ibánez L, López-Bermejo A 

Int J Obes, 34, 1365-1370 (2010) 


Pubertal metformin therapy to reduce total, visceral, and 

hepatic adiposity 

Ibáñez L, Lopez-Bermejo A, Diaz M, Marcos MV, de Zegher F 

J Pediatr, 156, 98-102e1 (2010) 



International project 

Infant manifestations of adult obesity susceptibility 

genotypes 

Research Unit, European Society for Paediatric 

Endocrinology, ESPE Research Unit Grant: 2010-2012 

Principal Investigators: Lourdes Ibáñez, Ken Ong, Francis 

de Zegher, David Dunger, Barbara Heude, Marie-Aline 

Charles 

Coordinator: Ken Ong 


Influence of early feeding in neurodevelopment and in 

subsequent cardiovascular risks in infants born small for 

gestational age 

MICINN-ISCIII, PI08/0443: 2008-2010 

Principal Investigator: Lourdes Ibáñez 

Associate investigators: Díaz M, Sebastiani G, Bosch L, del 

Rio L, Jiménez R, Hernández A, Gómez-Roig MD 

Stabilization programme for researchers and research 

support technicians and intensification of research 

activities in the Spanish health service 

MICINN-ISCIII, INT10/205: 2010 


IIntrauterine restriction and endocrine-metabolic 

abnormalities (proficient post-doc contracts in health 

research «Sara Borrell») 

MICINN-ISCIII, CD10/00234: 2010-2014 

Principal Investigator: David Sánchez Infantes 


Ovarian hyperandrogenism and polycystic ovaries in 

adolescence: the influence of birthweight and postnatal 

body mass index 

Hospital Sant Joan de Déu, AFR 08/004: 2008-2010 


Associate investigator: Nuria Conde 

Endocrine-metabolic profile and body composition in 

infants born large-for-gestational age 

Hospital Sant Joan de Déu, AFR 09/00020: 2009-2011 


Associate investigator: Miriam Pérez Cruz 

The influence of the erythrocyte fatty acid profile (as a 

surrogate of lipid intake in pregnant women during the 

third trimester) on postnatal growth, and on the adipokine 

profile in newborns born both small and appropriate for 

gestational age 

Hospital Sant Joan de Déu, AFR 10/00026: 2010-2012 


Associate investigator: Nuria Sanz 

Private funds 

Genetic and molecular factors influencing the development 

of visceral adiposity and its interaction with prenatal and 

postnatal growth in prepubertal children 

Nutribén, 10 Premio de Investigación Pediátrica: 2008-2010 

Principal Investigator: Abel López Bermejo 

Associate investigator: Lourdes Ibáñez 

The effects of early feeding and genetic polymorphisms 

related to metabolic syndrome and adipose tissue on 

visceral adiposity and intima media thickness in infants and 

children born small-for-gestational age 

Nutribén, 11 Premio de Investigación Pediátrica: 2009-2011 


Associate investigators: Abel López Bermejo, Marta 

Díaz, Paula Casano, Martí Iriondo, Isabel Iglesias, 

Carme Valls 



66 CibeRdem

The effects of metformin on cardiovascular risk factors in 

prepubertal children born small for gestational age without 

postnatal catch-up growth, currently treated with growth 

hormone 

Pfizer, PCP00046: 2009-2011 


Associate investigators: Paula Casano, Marta Díaz, Carme 

Valls, María Victoria Marcos 






CIBERDEM groups: L Ibáñez, X Correig, L Masana 


Endocrine-metabolic and body composition effects of 

metformin administration in prepubertal children with a 

low birthweight for gestational age, postnatal catch-up 

growth and risk markers for the metabolic syndrome. 

Phase II 


Sanitaria, EC08/00160: 2008-2010 

Name of the participants: Ibáñez L (PI), Casano P, Diaz M, 

Valls C, del Rio L, Marcos MV, Enríquez G, Sebastiani G, 

Hollenberg G, Fortea E and Cortés R (researchers) 

Cumulative gain in total and abdominal fat mass in prepubertal 

girls (age ~ 8 years) with a history of low birthweight and precocious 

pubarche, who were randomized to remain untreated (n=19; 

open circles) or to receive metformin (n=19; closed circles) for 4 yr, 

and who were then followed for 1 yr without intervention. Pubertal 

metformin treatment reduced fat gain not only through puberty, but 

also beyond puberty. Mean and 95% CI are shown. Difference in 

rate of change between subgroups significant by repeated-measures 

ANOVA. Image from: J Pediatr, 2010. 

Effects of the addition of metformin to growth hormone 

therapy on cardiovascular risk factors in prepubertal short 

children born small for gestational age. Phase II 


Sanitaria, EC10/0031: 2010-2012 

Name of the participants: Casano P (PI), Ibáñez L, Diaz M 

and Sebastiani G (researchers) 

Ethynil-estradiol-cyproterone acetate versus low-dose 

pioglitazone + flutamide + metformin in adolescents with 

hyperinsulinemic ovarian hyperandrogenism: Effects on 

parameters of chronic inflammation and on risk factors of 

type 2 diabetes and cardiovascular risk. Phase II 


Sanitaria, PI09/90444: 2009-2011 

Name of the participants: Ibáñez L (PI), Diaz M, Casano P, 

López-Bermejo A, Marcos MV, Mir I, Moran E and Salvador 

C (researchers) 

Comparative study of subcutaneous insulin pump, 

glargine insulin and NPH in diabetic children aged 0-6 yr. 

Phase II 


Sanitaria, EC07/90900: 2009-2011 

Name of the participants: Torres M (PI), Casano P, Díaz R, 

Jaramillo A, Anguita C, Gómez A and Marin S (researchers) 

Changes over 4 months (mean ± SEM) in total fat mass (by absorptiometry), 

abdominal (abd) subcutaneous (subc) fat (by magnetic 

resonance imaging), high-molecular-weight adiponectin (HMW adipo) 

and follistatin in short SGA children, before (N=18; open bars) 

and during (N=35; shaded bars) growth hormone (GH) treatment. 

*p


Insulin resistance in children: consensus, perspective, and 

future directions 



Institution: Consensus Meeting (ESPE-LWPES-ISPAD- 

APPES-APEG-SLEP-JSPE) 

Authors: Levy-Marchal C, Arslanian S, Cutfield W, Sinaiko A, 

Druet C, Marcovecchio ML, Chiarelli F; ESPE-LWPES-ISPAD- 

APPES-APEG-SLEP-JSPE; Insulin Resistance in Children 

Consensus Conference Group 

Patents 

International patent 

Composition comprising an androgen receptor blocker and 

an insulin sensitizing agent and use thereof for treatment of 

polycystic ovary syndrome 

Patent application number: PCT/BE 02/00052 

Inventors: Francis de Zegher, Lourdes Ibáñez 

University of Leuven and University of Barcelona (2010) 

Awards 

Accésit Premio Merck-Serono de Investigación de la Sociedad 

Española de Endocrinología Pediátrica. Original: Abdominal 

fat partitioning and high-molecular-weight adiponectin in short 

children born small-for-gestational-age. Hospital Sant Joan de 

Déu (2010) 

Awardees: Ibáñez L, López-Bermejo A, Diaz M, Marcos 

MV, Casano P, de Zegher F ■ 

68 CibeRdem

Lipids and Arteriosclerosis Research Unit 

Institut d’Investigació Sanitària Pere Virgili, Hospital Universitari Sant Joan de Reus 

www.iispv.cat 

Principal Investigator Lluís Masana luis.masana@urv.cat Research directors Josep Ribalta, Rosa Solà Senior researchers Anna Cabré, 

Joan Carles Vallvé Associate researcher Núria Plana Nutritionist Jordi Merino Postdoctoral fellows Montserrat Guardiola, Rosa Maria Valls 

PhD students Gemma Aragonès, Úrsula Catalán, Raimon Ferré, Marta González, Iolanda Lázaro, Isabel Martorell, Anna Pedret, Paula 

Saavedra Lab manager Josefa Girona Lab technicians Mercedes Heras, Carme Buixadera, Sara Fernández, Roser Rosales Administrative 

staff Sílvia Solé 











Spin-offs: 1 

PhD theses: 4 

Awards: 1 

Keywords 

Genetics type 2 diabetes. Insulin sensitivity and resistance. 

Metabolic syndrome. Biomarkers and Imaging. Prevention 

of type 2 diabetes. Endothelium. Macrovascular disease. 

Nutrigenomics. 


-Atherogenic dyslipidaemia in diabetes, obesity and 

metabolic syndrome. 

-The characterization of plasma lipoprotein subclasses by 

NMR, metabolomics and lipidomics. 

-Adipose tissue dysfunction as a major determinant of AD. 

-Fatty Acid-Binding Proteins (FABPs) and insulin resistance 

in different tissues. 

-Fatty acids and adipokine-induced endothelial dysfunction. 

-AD and subclinical atherosclerosis. 

-FFA, extracellular matrix and artery wall dysfunction in diabetes. 

-The epigenetics of atherosclerosis. 


69

-The impact of nutrition on metabolic and cardiovascular risk. 

-Nutrigenomics. 

Publications* 


APOH is increased in the plasma and liver of type 2 diabetic 

patients with metabolic syndrome 

Castro A, Lázaro I, Selva DM, Céspedes E, Girona J, Plana 

N, Guardiola M, Cabré A, Simó R, Masana L 


IF: 4.522 first decile. With other CIBERDEM groups: R Simó 

Effect of nut consumption on oxidative stress and the 

endothelial function in metabolic syndrome 

López-Uriarte P, Nogués R, Saez G, Bulló M, Romeu M, 

Masana L, Tormos C, Casas-Agustench P, Salas-Salvadó J 

Clin Nutr, 29, 373-380 (2010) 

IF: 3.247 first quartile. With other CIBERs: CIBEROBN 

Effect of the long-term regular intake of virgin olive oil on 

the phenolic metabolites in human fasting plasma 

Valls RM, Soler A, Girona J, Heras M, Romero MP, Covas MI, 

Solà R, Masana L, Motilva MJ 

J Pharm Biomed Anal, 53, 68-74 (2010) 

IF: 2.453 second quartile. With other CIBERs: CIBEROBN 

FABP4 plasma levels are increased in familial combined 

hiperlipidemias 

Cabré A, Lázaro I, Cofán M, Jarauta E, Plana N, Garcia-Otín 

AL, Ascaso JF, Ferré R, Civeira F, Ros E, Masana L 



R Carmena. With other CIBERs: CIBEROBN 

Fatty acid-binding protein 4 is associated with endothelial 

dysfunction in patients with type 2 diabetes 

Aragonès G, Ferré R, Lázaro I, Cabré A, Plana N, Merino J, 

Heras M, Girona J, Masana L 



Olive oil and health: summary of the II international conference 

on olive oil and health consensus report, Jaén and Córdoba 

(Spain) 2008 

López-Miranda J, Pérez-Jiménez F, Ros E, De Caterina R, 

Badimón L, Covas MI, Escrich E, Ordovás JM, Soriguer F, 

Abiá R, de la Lastra CA, Battino M, Corella D, Chamorro- 

Quirós J, Delgado-Lista J, Giugliano D, Esposito K, Estruch 

R, Fernandez-Real JM, Gaforio JJ, La Vecchia C, Lairon D, 

López-Segura F, Mata P, Menéndez JA, Muriana FJ, Osada 

J, Panagiotakos DB, Paniagua JA, Pérez-Martinez P, Perona 

J, Peinado MA, Pineda-Priego M, Poulsen HE, Quiles JL, 

Ramírez-Tortosa MC, Ruano J, Serra-Majem L, Solá R, Solanas 

M, Solfrizzi V, de la Torre-Fornell R, Trichopoulou A, Uceda M, 

Villalba-Montoro JM, Villar-Ortiz JR, Visioli F, Yiannakouris N 

Nutr Metab Cardiovasc Dis, 20, 284-294 (2010) 

IF: 3.517 first quartile. With other international groups. With other 

CIBERDEM groups: F Soriguer. With other CIBERs: CIBEROBN 

Polyunsaturated fatty acids down-regulate in vitro expression 

of the key intestinal cholesterol absorption protein NPC1L1: 

no effect of monounsaturated nor saturated fatty acids 

Alvaro A, Rosales R, Masana L, Vallvé JC 

J Nutr Biochem, 21, 518-525 (2010) 


Soluble fibre (Plantago ovata husk) reduces plasma 

low-density lipoprotein (LDL) cholesterol, triglycerides, 

insulin, oxidised LDL and systolic blood pressure in 

hypercholesterolaemic patients: A randomised trial 

Solà R, Bruckert E, Valls RM, Narejos S, Luque X, Castro- 

Cabezas M, Doménech G, Torres F, Heras M, Farrés X, 

Vaquer JV, Martínez JM, Almaraz MC, Anguera A 


IF: 4.522 first decile. With other CIBERDEM groups: F Soriguer 

The APOA5-1131 T>C variant enhances the association 

between RBP4 and hypertriglyceridemia in diabetes 

Cabré A, Lázaro I, Girona J, Manzanares JM, Marimón F, 

Plana N, Guardiola M, Heras M, Masana L 



Monitoring cells in the cell-culture cabinet. 

The apolipoprotein A5 gene predisposes Caucasian children 

to elevated triglycerides and vitamin E (Four Provinces Study) 

Guardiola M, Ribalta J, Gómez-Coronado D, Lasunción MA, 

de Oya M, Garcés C 





70 CibeRdem

Review 

Pitavastatin - from clinical trials to clinical practice 

Masana L 

Atheroscler Suppl, 11, 15-22 (2010) 


Editorial 

Progress in understanding postprandial dyslipidaemia: 

Second International Symposium on the Role of Chylomicrons 

in Disease l 

Watts GF, Ribalta J 

Atheroscler Suppl, 11, 1-2 (2010) 


Book chapter 

Book: Formación en Hipertrigliceridemias. JF Ascaso (ed), 

Equalmás 5 SL (2010) 

Chapter: Hipertrigliceridemias. Concepto y valores de 

corte 

Authors: Masana L, Pérez A 

Pages: 17-34 



Dislipemia aterógena de la obesidad, síndrome metabólico 

y diabetes tipo 2: caracterización metabólica y mecanismos 

patogénicos 

FIS, PI081409: 2008-2011 

Principal Investigator: Lluís Masana 

Associate investigator: Jesús Brezmes 

CIBERDEM groups: L Masana, X Correig 

Caracterización bioquímica, metabólica y genética de la 

hipertrigliceridemia asociada a alto riesgo cardiovascular 

FIS, PI081579: 2008-2011 

Principal Investigator: Josep Ribalta 

Associate investigator: Nicolau Cañellas 

CIBERDEM groups: L Masana, X Correig 





CIBERDEM groups: L Masana, F Blanco Vaca, R Carmena, 

X Correig, M Vázquez Carrera 





CIBERDEM groups: L Masana, L Ibáñez, X Correig 



CIBERDEM Biobank Nodes: L Masana, R Gomis, A Novials, J 

Vendrell, L Castaño, M Serrano Ríos, F Soriguer, R Carmena, 

F Blanco Vaca 


MK-0524A Estudio multicéntrico aletorizado, doble ciego, con 

grupos paralelos y de 12 semanas de tratamiento. Phase III 

Merck Sharp & Dohme: 2007-2010 

Researchers: Lluís Masana, Núria Plana, Raimon Ferré 

UCR 2007-01 Investigación de la genética del riesgo de 

padecer una enfermedad coronaria en voluntarios. Phase IV 

UNILEVER UK Central Resources Ltd: 2008-2012 


Cardiovascular Fixed Combination Pill ASR: Ensayo clínico 

farmacodinámico de la combinación a dosis fijas de ácido 

acetilsalicílico, simvastatina y ramipril (Cardiovascular 

Polypill); Colesterol LDL. Phase III 

Laboratoris Ferrer: 2010 


Aceite de oliva virgen y función de las lipoproteínas de alta 

desnsidad (HDL), un modelo de preparación especializada 

de un alimento funcional 

Ministerio de Ciencia e Innovación, AGL2009-13517-C03-03: 

2008-2012 

Research Director: Rosa Solà 

Ensayo de intervención nutricional aleatorizado, 

doble ciego, controlado con placebo, para valorar la 

eficacia y la seguridad de yogur suplementado con 

mobilee comparado con yogur no suplementado, 

sobre la función articular, evolución ecográfica y 

calidad de vida de adultos con gonalgia de baja 

intensidad 

Ministerio de Ciencia e Innovación, CENIT: 2010-2011 

Research Director: Rosa Solà 

Carotid intima-media thickness assessment in patients. 


71

An international multicentre, randomized, parallel group, 

double-blind trial to evaluate different close combinations 

of Lercadinipine and Enalapril in comparison with each 

component administered alone and with placebo in patients 

with essential hypertension. Phase III 

Recordati España, SL: 2010-2011 


Spin-offs 

Beyond Food SL 

Description: Support to industry for the validation of 

functional food 

Researchers: L Masana, R Solà, JC Vallvé, J Ribalta, J 

Girona, C Prats 

Collaborating institution: Universitat Rovira i Virgili 

Year of creation: 2007 

PhD theses 

Estudio de la variabilidad del gen CRABP2 en el 

metabolismo lipídico y de la influencia del ácido retinoico 

en el endotelio vascular 

Author: Juliana Salazar Blanco 

University: Universitat Rovira i Virgili 

Thesis defense date: January 27, 2010 

Implementation of in vitro screening assays to test 

inflammation, thrombosis and endothelial function in cells 

Author: Laia Pons Llecha 



FABP4 i biomarcadors de disfunció endotelial. Estudi clínic 

i in vitro. 

Author: Gemma Aragonès Bargalló 



Regulació de la FABP4 depenent de NRF2 en macròfags. 

Author: Iolanda Lázaro López 



Awards 

IAS Visiting Fellowship Award, International Atherosclerosis 

Society (2010) 

Awardee: Montserrat Guardiola ■ 

72 CibeRdem

Diabetobe 

Hospital Clínico San Carlos, Madrid 

www.madrid.org 

Principal Investigator Manuel Serrano Ríos mserrano.hcsc@salud.madrid.org Associate researchers María Teresa Martínez Larrad, 

Jesús Álvarez Fernández Represa, Arturo Corbatón, Vicente Estrada, Cristina Fernández Research assistants Covadonga Caso, Bernat 

Jiménez, Carina Zabena Lab technicians Carmen Obiang, Noelia Rodríguez Administrative staff María del Mar González 


Publications: 1, in the second quartile 






PhD theses: 2 

Keywords 

Epidemiology. Genetics type 2 diabetes. Genomics. Metabolic 

syndrome. Prevention of type 1 diabetes. Proteomics. 


-A genowide study of the Spanish population. Search of 

loci for FG, FI, HbA1C and others. 

-A genomic, lipidomic and proteomic study of subcutaneous/ 

abdominal adipose tissue and its relationship to type 2 

diabetes and obesity. 

-Genes and inflammatory markers in children with obesity 

and/or metabolic syndrome. 

-Analysis of genetic markers, circulating adipokines and 

insulin-resistance status in HIV naïve patients and those 

undergoing retroviral treatment. 

-Analysis of genetic markers, circulating adipokines and 

insulin-resistance status in polycystic ovary syndrome and 

obesity. 

-Nutritional primary prevention of type 1 diabetes in children 

(TRIGR). 

Publications* 


WWOX gene is associated with HDL cholesterol and 

triglyceride levels 

Sáez ME, González-Pérez A, Martínez-Larrad MT, Gayán J, 

Real LM, Serrano-Ríos M, Ruiz A 




73

BMC Med Genet, 11, 148 (2010) 


Books 

Obesity, Elsevier (2010) 

Authors: Manuel Serrano Ríos, José M Ordovás, José A 

Gutiérrez Fuentes 

Type 2 Diabetes Mellitus, Elsevier (2010) 

Authors: Manuel Serrano Ríos, José A Gutiérrez Fuentes 

Book chapters 

Book: Obesity, Elsevier (2010) 

Chapter: Obesity and Type 2 Diabetes Mellitus. The 

reciprocal impact 

Authors: Manuel Serrano Ríos, José A Gutiérrez Fuentes 

Pages: 215-232 

Book: Type 2 Diabetes Mellitus, Elsevier (2010) 

Chapter: Classification of Dibetes Mellitus: Criteria for Diagnosis 

Authors: Manuel Serrano Ríos, Jesús Reviriego, José A 

Gutiérrez Fuentes 

Pages: 1-23 


International project 

Nutritional Primary Prevention of Type1 Diabetes in Children 

NIH, QLK1-CT-2002-00372: 2002-2012 

Principal Investigator: Manuel Serrano Ríos 

Private funds 

Morbi-Mortabilidad y Caracterización Genética en el 

ámbito Rural y Urbano de la Provincia de Segovia 

Fundación Mutua Madrileña, FMM08: 2008-2010 

Principal Investigators: Cristina Fernández Pérez, Manuel 

Serrano Ríos 

An analysis of the change in the distribution of body fat and 

the relationship with adipokine levels in patients with HIV 

undergoing retroviral treatment 

Fipse, 236697/07/07: 2007-2010 

Principal Investigators: Vicente Estrada, Manuel Serrano Ríos 

Metabolic syndrome, genes, inflammation markers 

Lilly SA: 2006-2011 

Principal Investigator: Manuel Serrano Ríos 

Fat tissue in morbid obesity: from histology to gene expression, proteomics and lipidomics. 

74 CibeRdem






CIBERDEM groups: M Serrano Ríos, F Blanco Vaca, 

R Carmena, F Soriguer 

The impact of overnutrition, diabetes-obesity, and 

undernutrition on the regulation of energy homeostasis in 

the central nervous system. From animal models to humans 

IODURE: 2009-2010 

Coordinator: Manuel Serrano Ríos 

CIBERDEM groups: M Serrano Ríos, C Álvarez, E Blázquez, 

D Burks, M Vallejo 



Coordinator: Federico Soriguer 

CIBERDEM groups: M Serrano Ríos, F Soriguer, R Carmena, 

L Castaño, R Gomis, J Vendrell 



CIBERDEM Biobank Nodes: M Serrano Ríos, R Gomis, 

A Novials, J Vendrell, L Masana, L Castaño, F Soriguer, 

R Carmena, F Blanco Vaca 


Alimentación para Personas Mayores (2010) 

Institution: Instituto Danone 

Authors: Manuel Serrano Ríos, Pilar López Nomdebeu, 

José Manuel Ribera Casado, Ana Sastre Gallego 

PhD theses 

Obesidad Mórbida. Estudio de expresión genética y 

análisis proteómico del tejido adiposo en individuos obesos 

mórbidos 

Author: Carina A Zabena 


Thesis defense date: 2010 

Prevalencia de obesidad según diferentes índices 

atropométricos en población adulta de la provincia de 

Segovia 

Author: María Dolores Martín Ríos 

University: Universidad Rey Juan Carlos 

Thesis defense date: 2010 ■ 


75

Diabetes and Metabolism Research Group 

Institut de Recerca Hospital Universitari Vall d’Hebron, Barcelona 

www.ir.vhebron.net 

Principal Investigator Rafael Simó rsimo@ir.vhebron.net Associate researchers Cristina Hernández, Albert Lecube, Jordi Mesa 

Postdoctoral fellows Marta García Ramírez, David Martínez Selva, Josep A Villena Research assistants Anna Barbosa, Lidia Corraliza 

PhD student Marta Villarroel Lab technician Lorena Ramos 













Awards: 2 

Keywords 

Clinical diabetes. Retinopathy. Weight regulation and 

obesity. Lipid metabolism. Metabolic syndrome. 


-The physiopathology of diabetic retinopathy. A new 

approach using integrated biological systems. 

-Insulin resistance and obesity: new pathogenic candidates 

and the study of co-morbidities. 

-Endothelial dysfunction, dyslipidaemia and cardiovascular 

disease in type 2 diabetes. 

-Non-invasive monitorization of blood glucose. The clinical 

development of a new system of glucose monitoring based 

on near-infrared technology. 

Publications* 


APOH is increased in the plasma and liver of type 2 diabetic 

patients with metabolic syndrome 

Castro A, Lázaro I, Selva DM, Céspedes E, Girona J, Plana 

N, Guardiola M, Cabré A, Simó R, Masana L 



76 CibeRdem


IF: 4.522 first decile. With other CIBERDEM groups: L Masana 

Asymptomatic sleep-disordered breathing in premenopausal 

women awaiting bariatric surgery 

Lecube A, Sampol G, Lloberes P, Romero O, Mesa J, Morell 

F, Simó R 

Obes Surg, 20, 454-461 (2010) 

IF: 2.934 first quartile. With other CIBERs: CIBERES 

Effect of intensive insulin therapy on macular biometrics, 

plasma VEGF and its soluble receptor in newly diagnosed 

diabetic patients 

Hernández C, Zapata MA, Losada E, Villarroel M, García- 

Ramírez M, García-Arumí J, Simó R 



Insulin resistance is related to impaired lung function in 

morbidly obese women: a case-control study 

Lecube A, Sampol G, Muñoz X, Lloberes P, Hernández C, 

Simó R 


IF: 2.762 second quartile. With other CIBERs: CIBERES 

Lipopolysaccharide-binding protein and soluble CD14 

in the vitreous fluid of patients with proliferative diabetic 

retinopathy 

Hernández C, Ortega F, García-Ramírez M, Villarroel M, 

Casado J, García-Pascual L, Fernández-Real JM, Simó R 

Retina, 30, 345-352 (2010) 


Metabolic fingerprints of proliferative diabetic retinopathy: 

an 1H-NMR-based metabonomic approach using vitreous 

humor 

Barba I, Garcia-Ramírez M, Hernández C, Alonso MA, 

Masmiquel L, García-Dorado D, Simó R 

Invest Ophthalmol Vis Sci, 51, 4416-4421 (2010) 


New pathogenic candidates for diabetic macular edema 

detected by proteomic analysis 

Hernández C, García-Ramírez M, Colomé N, Villarroel M, 

Corraliza L, García-Pascual L, Casado J, Canals F, Simó R 

Diabetes Care, 33, e92 (2010) 


The relationships between IGF-1 and CRP, NO, leptin, 

and adiponectin during weight loss in the morbidly 

obese 

Pardina E, Ferrer R, Baena-Fustegueras JA, Lecube A, Fort 

JM, Vargas V, Catalán R, Peinado-Onsurbe J 


IF: 2.934 first quartile. With other CIBERs: CIBEREHD 

Type 2 diabetes impairs pulmonary function in morbidly 

obese women: a case-control study 

Lecube A, Sampol G, Muñoz X, Hernández C, Mesa J, Simó R 

Diabetologia, 53, 1210-1216 (2010) 

IF: 6.551 first decile. With other CIBERs: CIBERES 

Review 

Iron in obesity. An ancient micronutrient for a modern 

disease 

Zafon C, Lecube A, Simó R 

Obes Rev, 11, 322-328 (2010) 


Book chapters 

Book: Experimental Approaches to Diabetic Retinopathy, 

Frontiers in Diabetes. Vol 20, Karger (eds HP Hammes and 

M Porta), Basel (2010) 

Chapter: Growth factors in the Diabetic Eye 

Authors: Simó R, Hernández C 

Book: Neurodegeneration: Theory, Disorders and Treatments, 

Nova Science Publishers (Ed McNeill AS), New York/USA 


Chapter: Retinal Neurodegeneration is an Early Event in 

the Pathogenesis of Diabetic Retinopathy: Therapeutic 

Implications 

Authors: Simó R, Hernández C 

Book: Permeability Barrier: Methods and Protocols, 

Humana Press, Springer (Ed Turksen K), New York 


Chapter: Measuring Permeability in Human Retinal 

Epithelial Cells (ARPE-19). Implications for the Study of 

Diabetic Retinopathy 

Authors: García Ramírez M, Villarroel M, Corraliza L, 

Hernández C, Simó R 

Book: Visual Dysfunction in Diabetes: The Science of 

Patient Impairment and Healthcare, Humana Press (eds 

J Tombran-Tink, CJ Barnstable, TW Gardner), New York 


Chapter: Neurodegeneration, Neuropeptides and Diabetic 

Retinopathy 

Authors: Hernández C, Villarroel M, Simó R 



Neurodegeneration as an early event in the pathogenesis 

of diabetic retinopathy. A study of the mechanisms involved 

and new therapeutic strategies 

European Association for the Study of Diabetes Foundation, 

EFSD-Sanofi/Aventis Programme: 2010-2011 

Principal Investigator: R Simó 

Associate investigators: C Hernández, M García Ramírez, 

M Villarroel, L Corraliza, L Ramos 


77


Impacto del uso de insulina en el riesgo de cáncer en 

pacientes con diabetes mellitus tipo 2 

Ministerio de Sanidad y Política Social, SAS/2377/2010: 



Associate investigator: IDIAP (Instituto de Investigación en 

Asistencia Primaria, Barcelona) 


diabética incipiente Estudio de los mecanismos implicados 

a través de un abordaje integrado de biología de sistemas 


2009-2011 

Principal Investigator: Rafael Simó 

Associate investigators: M García Ramírez, M Villarroel, L 

Corraliza 

CIBERDEM groups: R Simó, X Correig 

Depósito de glucógeno en la retina y neurodegeneración: 

un nuevo mecanismo implicado en la patogénesis de la 

retinopatía diabética 

Instituto de Salud Carlos III, FIS, PI10/01219: 2010-2013 

Principal Investigator: C Hernández 

Associate investigators: M García Ramírez, L Corraliza 

Role of PGC-1beta in white adipose tissue and its 

contribution to the development of obesity and type 2 

diabetes 

Ministerio de Ciencia e Innovación, SAF2008-03644: 2009-2011 

Principal Investigator: Josep A Villena 

Function of PGC-1® and PGC-1® coactivators in adipose 

tissue. Implications in obesity and insulin resistance 

Ministerio de Ciencia e Innovación, RYC-2006-002429: 

2007-2012 


Sex hormone-binding globulin (SHBG): Identificación de 

los mecanismos moleculares que regulan su expresión 

y papel en la distribución de la grasa corporal y en el 

desarrollo de la diabetes mellitus (DM) tipo2 

Instituto de Salud Carlos III, Programa Miguel Servet, 

CP08/00058: 2009-2011 

Principal Investigator: David M Selva 

Papel de la sex hormone-binding globulin (SHBG) y de los 

esteroides sexuales en la distribución de la grasa corporal 

y en la aparición de la diabetes mellitus tipo 2 

Instituto de Salud Carlos III, FIS, PI09/0144: 2009-2011 

Principal Investigator: David M Selva 

Associate investigator: L Ramos 

Diabetes and insulin resistance 

Cardiovascular diseases network (RECAVA), Instituto de 

Salud Carlos III: RD06/0014/1014: 2006-2010 


Associate investigators: C Hernández, M García Ramírez 


Suport a grups de recerca 

Generalitat de Catalunya, AGAUR, 2009SGR 739: 

2009-2013 



M Villarroel, L Corraliza, A Lecube, J Mesa, DM Selva, L 

Ramos 

Private funds 


diabética incipiente 

Fundación Sociedad Española de Endocrinología y 

Nutrición, Beca Novo Nordisk: 2009-2010 

Principal Investigator: C Hernández 

Associate investigators: R Simó, M García Ramírez, M 

Villarroel, L Corraliza, L Ramos 

Estudio del efecto neuroprotector del fenofibrato y 

candesartan en la retinopatía diabética 

Fundación Sociedad Española de Endocrinología y 

Nutrición, Beca Sanofi Aventis: 2009-2010 



M Villarroel, L Corraliza, L Ramos 

Implication of oestrogen-related receptors in the etiology 

of diabetic cardiomyopathy: role as potential targets for 

treatment of diabetic cardiomyopathy 

Fundació La Marató de TV3, 082610: 2009-2011 


Neuroprotection by enhancing GLP-1R signalling, a 

new therapeutic strategy in the early stages of diabetic 

retinopathy 

Novo Nordisk SA: 2010-2012 



M Villarroel, L Corraliza, DM Selva 

Desarrollo de variantes moleculares y análogos de 

somatostatina con potencial aplicación en retinopatía 

diabética y otras enfermedades oculares 

BCN Peptides, SA: 2009-2010 



M Villarroel 

Efecto del fenofibrato sobre la permeabilidad de la 

barrera retiniana externa en cultivos de células de epitelio 

pigmentario de retina 

78 CibeRdem

Solvay, SA: 2008-2010 



M Villarroel, L Corraliza 







CIBERDEM groups: R Simó, D Burks, A Martínez Valverde 


and their involvement in the ethiogenesis of diabetes 

mellitus 



CIBERDEM groups: R Simó, R Gomis, JJ Guinovart 






CIBERDEM groups: R Simó, J Vendrell, A Zorzano, 

J Balsinde, AM Gómez Foix, E Montanya, S Fernández 

Veledo, M Vázquez Carrera 

DEFEND-2: Durable-Response Therapy Evaluation for 

Early- or New-Onset Type 1 Diabetes. TRX4_DM_007_ 

EU_08. Phase III 

Constella Group SA: 2010-2012 

Name of the participants: C Hernández (researcher), R 

Simó (coordinator) 

A 26-week, multinational, multi-centre, open-labelled, twoarm, 

parallel, randomised, treat-to-target, efficacy and 

safety comprisons of soluble insulin analogue combination 

(SIAC) once daily (OD) and insulin glargine OD both in 

combination with metformin in insulin-naïve subjects with 

type 2 diabetes inadequately controlled on oral antidiabetic 

drugs (OADs). NN5401-3590. Phase III 

Novo Nordisk SA: 2009-2010 

Name of the participants: A Lecube (researcher), R Simó 

(coordinator) 

Estudio de extension de 26 semanas, multinacional, 

multicéntrico, abierto, de dos grupos paralelos y con ajuste 

de dosis para comparar la eficacia y seguridad de una 

combinación de un análogo soluble de insulina (SIAC) 

administrado una vez al día (OD) frente a insulina glargina 

(OD), ambas en combinación con metformina, en sujetos 

con Diabetes tipo 2. NN5401-3726. Phase III 

Novo Nordisk SA: 2010-2011 






CIBERDEM groups: R Simó, X Correig, E Montanya, 

HF Escobar Morreale, J Vendrell 


Estudio multicéntrico, de 24 semanas seguido por 

una extensión, aleatorizado, doble ciego controlado 

con placebo y de grupos paralelos, para evaluar 

la eficacia y seguridad de AVE0010 añadido a 

metformina en pacientes con diabetes tipo 2 no 

controlados adecuadamente con metformina. 

EFC6014. Phase III 


Name of the participants: R Simó, J Mesa and A Lecube 

(researchers) 

DEFEND-1: Durable-Response Therapy Evaluation for 

Early- or New-Onset Type 1 Diabetes. TRX4_DM_007_ 

EU_08. Phase III 

Constella Group SA: 2009-2011 

Name of the participants: C Hernández (researcher), R 

Simó (coordinator) 

Immunohistochemistry of ARPE-19 cell monolayer. Tight junction 

protein ZO-1 appears in red and F-actin network of the cytoskeleton 

in green. Nuclei were stained with DAPI (blue). Bar: 20 µm. 


79

Name of the participants: A Lecube (researcher), J Mesa 

(coordinator) 

Tratamiento combinado de insulina glargina o sitagliptina 

en pacientes con diabetes tipo 2, no controlados 

suficientemente con un tratamiento previo con metformina 

y con insulina glargina o sitagliptina. EXT_LANTU_ C 

_02761. Phase III/IV 


Name of the participant: J Mesa (researcher) 

A 52 week randomised, controlled, open label, multicentre, 

multinational treat-to-target trial comparing efficacy and 

safety of SIBA and insulin glargine both administered 

once daily in a basal-bolus regimen with insulin aspart as 

mealtime insulin + treatment with metformin, + pioglitazone 

or both in subjects with type 2 diabetes currently treated 

with insulin qualifying for intensified treatment. NN1250- 

3582. Phase III 

Novo Nordisk SA: 2009-2010 


A 78 week open label extension to trials assessing the safety 

and efficacy of BI 10773 as monotherapy or in combination 

with Metformin in type 2 diabetic patients. 1245.24. Phase III 

Boehringer Ingelheim: 2009-2010 


An open label extension to trials assessing the safety and 

efficacy of BI 10773 as monotherapy in type 2 diabetic 

patients. 1245.25. Phase III 

Boehringer Ingelheim: 2010-2014 


Estudio multicéntrico aleatorizado, doble ciego y controlado 

con placebo para evaluar resultados cardiovasculares 

después del tratamiento con alogliptina en combinación 

con la asistencia habitual en sujetos con diabetes tipo2 y 

síndrome coronario agudo. SYR-322_302. Phase III 

Takeda Global Resarch: 2009-2013 


Awards 

Premio Dr. Josep Trueta a la trayectoria de investigación 

dentro del ámbito de las Ciencias de la Salud, Academia 

de Ciencias Médicas y de la Salud de Catalunya y Baleares 


Awardee: Rafael Simó 

Premio Sanofi Aventis a la trayectoria en diabetes para 

jóvenes endocrinólogos, Fundación Sociedad Española de 

Endocrinología y Nutrición (2010) 

Awardee: Albert Lecube ■ 

80 CibeRdem

Endocrinology and Nutrition Service 

Hospital Regional Universitario Carlos Haya, Málaga 

www.carloshaya.net 

www.imabis.org 

Principal Investigator Federico Soriguer federico.soriguer.sspa@juntadeandalucia.es Associate researchers María Cruz Almaraz, Isabel 

Esteva de Antonio, Juan Miguel Gómez, María Stella González, Sonsoles Morcillo, Gabriel Olveira, Gemma Rojo, María Soledad Ruiz de 

Adana, Sergio Valdés Postdoctoral fellow Eva García Research assistants Isabel Cardona, Sara García, Francisca Linares, Gracia María 

Martín, Nuria Porras Nursing assistant M José Moreno PhD students Carolina Gutiérrez, Juan José Haro, Elehazara Rubio, Gracia María 

Martín Lab technician María de Haro Martín Administrative staff Patricia González 













PhD theses: 1 

Keywords 

Epidemiology. Insulin therapy. Metabolic syndrome. 

Prediction/prevention of type 2 diabetes. Weight regulation 

and obesity. 


-The biomolecular epidemiology of diabetes, obesity and 

metabolic syndrome (Pizarra Study, Egabro Study, Di@bet. 

es Study, Di@bet.an Study). 

-The study of insulin resistance in patients with extreme 

obesity undergoing bariatric surgery. 

-Fatty acids, insulin resistance and adipocyte metabolism. 

-New technologies applied to the treatment of type 1 diabetes. 

Publications* 


Intake and home use of olive oil or mixed oils in relation to 

healthy lifestyles in a Mediterranean population. Findings 




81

from the prospective Pizarra study 

Soriguer F, Almaraz MC, García-Almeida JM, Cardona I, 

Linares F, Morcillo S, García-Escobar E, Dobarganes MC, 

Olveira G, Hernando V, Valdes S, Ruiz-de-Adana MS, 

Esteva I, Rojo-Martínez G 



Jejunal wall triglyceride concentration of morbidly obese 

persons is lower in those with type 2 diabetes mellitus 

Soriguer F, García-Serrano S, Garrido-Sánchez L, Gutierrez- 

Repiso C, Rojo-Martínez G, Garcia-Escobar E, García- 

Arnés J, Gallego-Perales JL, Delgado V, García-Fuentes E 



Nutritional regulation of interleukin-6 release from 

adipocytes 

García-Escobar E, Rodríguez-Pacheco F, García-Serrano 

S, Gómez-Zumaquero JM, Haro-Mora JJ, Soriguer F, Rojo- 

Martínez G 



Olive oil and health: summary of the II international conference 

on olive oil and health consensus report, Jaén and Córdoba 

(Spain) 2008 

López-Miranda J, Pérez-Jiménez F, Ros E, De Caterina R, 

Badimón L, Covas MI, Escrich E, Ordovás JM, Soriguer F, 

Abiá R, de la Lastra CA, Battino M, Corella D, Chamorro- 

Quirós J, Delgado-Lista J, Giugliano D, Esposito K, Estruch 

R, Fernandez-Real JM, Gaforio JJ, La Vecchia C, Lairon D, 

López-Segura F, Mata P, Menéndez JA, Muriana FJ, Osada 

J, Panagiotakos DB, Paniagua JA, Pérez-Martinez P, Perona 

J, Peinado MA, Pineda-Priego M, Poulsen HE, Quiles JL, 

Ramírez-Tortosa MC, Ruano J, Serra-Majem L, Solá R, 

Solanas M, Solfrizzi V, de la Torre-Fornell R, Trichopoulou 

A, Uceda M, Villalba-Montoro JM, Villar-Ortiz JR, Visioli F, 

Yiannakouris N 



other CIBERDEM groups: L Masana. With other CIBERs: 

CIBEROBN 

PPARgamma expression after a high-fat meal is associated 

with plasma superoxide dismutase activity in morbidly 

obese persons 

Garcia-Fuentes E, Murri M, Garrido-Sanchez L, Garcia- 

Serrano S, García-Almeida JM, Moreno-Santos I, Tinahones 

FJ, Macias-Gonzalez M 

Obesity (Silver Spring), 18, 952-958 (2010) 

IF: 3.366 second quartile. With other CIBERs: CIBEROBN 

Soluble fibre (Plantago ovata husk) reduces 

plasma low-density lipoprotein (LDL) cholesterol, 

triglycerides, insulin, oxidised LDL and systolic 

blood pressure in hypercholesterolaemic patients: A 

randomised trial 

Solà R, Bruckert E, Valls RM, Narejos S, Luque X, 

Castro-Cabezas M, Doménech G, Torres F, Heras 

M, Farrés X, Vaquer JV, Martínez JM, Almaraz MC, 

Anguera A 


IF: 4.522 first decile. With other CIBERDEM groups: L Masana 



REPROBESITY: Search For New Therapeutic Agents 

Against Complicated Obesity By Reprofiling Existing Drugs 

European Union, Seventh Framework Programme, FP7- 

HEALTH-2007-B: 2009-2012 

Principal Investigator: Fernando Rodríguez de Fonseca 


Estudio de los polimorfismos de los genes Ar, Er beta y 

Cyp19, y de reordenaciones en los cromosomas X e Y, en 

dos poblaciones de personas con trastorno de identidad 

de género (TIG) 

Ministerio de Ciencia e Innovación, Proyectos de 

Investigación Fundamental no orientada: 2010-12 

Principal Investigator: Eduardo Pásaro 

Associate investigators: Rosa Fernández, Blanca Laffon, 

Antonio Guillamón, Isabel Esteva, Maricruz Almaraz, 

Raquel Yahyahoui, Juan Haro, Esther Gómez Gil 

Epigenética y Riesgo de diabetes mellitus tipo 2 

Instituto de Salud Carlos III, PS09/0217: 2010-2012 

Principal Investigator: Sonsoles Morcillo Espina 

Associate investigators: Juan Miguel Gómez Zumaquero, 

Elehazara Rubio Martín, Gracia María Martín Núñez, 

Gabriel Olveira, M Soledad Ruiz de Adana, Isabel Esteva 

de Antonio 

Estudio del papel biológico de la SCD1 como posible 

mediador entre la obesidad e insulinresistencia en 

individuos obesos mórbidos desde una aproximación in 

vivo e in vitro 


Principal Investigator: Eduardo García Fuentes 

Associate investigators: Sara García Serrano, Carolina 

Gutiérrez Repiso, Gabriel Olveira, Eva García Escobar, 

José Luis Gallego Perales, Juan García Arnés 

Adaptación psicosocial, calidad de vida, y demanda 

de asistencia sanitaria durante 10 años en personas 

diagnosticadas de trastorno de la identidad de género 

Ministerio de Igualdad, IMG 2009-PI040964: 2009-2011 

Principal Investigator: Esther Gómez Gil 

Associate investigators: I Esteva, MC Almaraz, J Martínez, 

A Guillamón, M Salamero, T Godás 

82 CibeRdem

Prevención de la Diabetes mellitus tipo 2. Estudio Egabro- 

Pizarra 

Instituto Salud Carlos III, PI08/1592: 2009-2011 

Principal Investigator: Gemma Rojo Martínez 

Associate investigators: Federico Soriguer, Sergio Valdés, 

Curra Linares, Juan Haro Mora, Raquel Yahyahoui, Francisco 

Rivas Ruiz, Pedro Benito López, María Sierra Corpas 

Estudio de la variabilidad genética de la delta-9-desaturasa 

en la población general y su asociación con la obesidad 

Instituto de Salud Carlos III, CP07/00187: 2008-2011 

Principal Investigator: Juan Miguel Gómez Zumaquero 

Estudio comparativo de terapia con infusores subcutáneos 

de insulina (isci) versus sistema integrado isci y sensor 

continuo de glucosa con transmisión a tiempo real por 

ondas. Impacto sobre variables metabólicas, psicológicas 

y de calidad de vida 

Fondo de Investigación Sanitaria, Evaluación de 

Tecnologías Sanitarias, PI 07/90330: 2008-2010 

Principal Investigator: M Soledad Ruiz de Adana Navas 

Associate investigators: Curra Linares, Isabel Cardona, 

Teresa Anarte, Alberto Machado, Marta Domínguez, 

José Tapia, María Lainez, Magdalena de la Higuera, M 

Inmaculada González Molero 

Impacto de las nuevas tecnologías en el tratamiento de 

la diabetes mellitus tipo 1: efectos en la calidad de vida, 

variables psicológicas y metabólicas 

Ministerio de Educación y Ciencia, SEJ07-63786/PSIC: 


Principal Investigator: M Teresa Anarte 

Associate investigators: Sergio Valdés, M Soledad Ruiz de 

Adana Navas 


Nuevos retos sobre el papel de las hormonas tiroideas 

en la regulación del peso corporal. Efecto de SNPs en 

el gen del receptor alpha de las hormonas tiroideas en 

la respuesta a una intervención sobre estilos de vida 

mediante dieta mediterránea y ejercicio físico en individuos 

con prediabetes. Estudio Egabro/Pizarra 

Consejería de Salud Junta de Andalucía, PI-0327-2010: 


Principal Investigator: Sergio Valdés Hernández 

Associate investigators: M Cruz Almaraz, Inmaculada 

González Molero, Isabel Cardona, Elehazara Rubio 

Martín 

Implicación del Transporte de Ácidos Grasos y del Factor 

de Crecimiento del Endotelio Vascular B (Vegf-B) en el 

Desarrollo de Diabetes. Estudio de Prevención Primaria de 

la Diabetes Tipo 2 

Consejería de Salud Junta de Andalucía, PI-0532-2010: 



Associate investigators: María José Leña Carrillo, Fuensanta 

Lima Rubio, Nuria Porras Pérez, Gabriel Olveira Fuster, 

Araceli Chicano Gálvez, Juan Miguel Gómez Zumaquero 

Estudio de la función tiroidea e ingesta de yodo en el periodo 

final de la gestación en mujeres embarazadas sanas 

Consejería de Salud Junta de Andalucía, PI 0501/2009: 

2009-2011 

Principal Investigator: Inés Velasco López 

Associate investigators: Federico Soriguer, Ernesto 

González, José Alberto Herrera, María Gallego, Jessica 

Martín, M José Garriga 

Papel del tejido adiposo y las adipoquinas en el desarrollo 

de Diabetes tipo 2. Un estudio de cohortes poblacional 

Consejería de Salud Junta de Andalucía, 0189/2008: 



Associate investigators: Juan Haro Mora, Nuria Porras, 

Isabel Esteva, M Cruz Almaraz, Curra Linares, Isabel 

Cardona, Carolina Gutiérrez, Stella González 

Prevención de la Diabetes mellitus tipo 2. Estudio Egabro 

Consejería de Salud Junta de Andalucía, 0188/2008: 2008-2010 

Principal Investigator: Federico Soriguer 

Associate investigators: Gabriel Olveira, Carolina Gutiérrez, 

Isabel Cardona, Stella González, Isabel Cardona, Juan 

Pedro López Siguero 

Genes candidatos y Dieta Mediterránea: prevalencia de 

Diabetes tipo 2 en Andalucía. Estudio Di@bet.an 


Principal Investigator: Sonsoles Morcillo Espina 

Associate investigators: Raquel Yahyahoui, Sergio Valdés, 

Francisca Linares, Sara García Serrano, Elehazara Rubio Martín, 

Juan Miguel Gómez Zumaquero, Isabel Esteva de Antonio 

Estudio del dimorfismo sexual metabólico y hormonal en 

personas transexuales durante el proceso de reasignación 

de sexo 


Principal Investigator: Isabel Esteva de Antonio 

Associate investigators: M Cruz Almaraz, Raquel Yahyahoui, 

Juana Martínez Tudela, Pilar Rocío Carrasco López 

Prevención de la Diabetes mellitus tipo 2. Estudio Egabro- 

Pizarra 

Consejería de Innovación Junta de Andalucía, P09- 

CTS-5125: 2010-2012 






83


Coordinator: FJ Chaves 

CIBERDEM groups: F Soriguer, F Blanco Vaca, R Carmena, 

M Serrano Ríos 




CIBERDEM groups: F Soriguer, R Carmena, L Castaño, R Gomis, 

M Serrano Ríos, J Vendrell 



CIBERDEM Biobank Nodes: F Soriguer, R Gomis, A Novials, 

J Vendrell, L Masana, L Castaño, M Serrano Ríos, R Carmena, 

F Blanco Vaca 


Estudio multicéntrico, aleatoriazdo, doble ciego controlado 

con fármaco activo para comparar el efecto del tratamiento 

a largo plazo (hasta 5 años) de 50 mg LAF237 bid con 

glimepirida a dosis de hasta 6mg/dia como terapia añadida 

en pacientes con diabetes Tipo 2 que no estén controlados 

adecuadamente con metformin a en monoterapia. 

CLAF237A2308 

Novartis: 2005-2011 

Efecto de la insulina glulisina en comparación con la 

insulina aspart y la insulina lispro cuando se administran 

mediante Infusión Subcutánea Continua de Insulina (ISCI) 

sobre parámetros específicos de la bomba en pacientes 

con Diabetes Mellitus tipo 1. APIDR_C_02083. Phase III 


RT-PCR on screen. 

Ensayo multicéntrico, abierto, aleatorizado, de dos grupos, 

paralelos para comparar el cambio en la distribución de 

grasa en sujetos con sobrepeso y obesos con diabetes 

tipo 2 tras 26 semanas de tratamiento con insulina detemir 

una vez al día frente a insulina nph una vez al día, ambas 

con insulina aspart a la hora de las comidas. NN 304 3614. 

Phase III 

Novo Nordisk: 2010-2012 

Estudio en fase II para evaluar la seguridad y eficacia de 

BI10773 administrado una vez al día durante 12 semanas, 

comparado con placebo y un brazo abierto con Sitagliptina 

en Diabetes tipo 2. 1245.10. Phase II 

AstraZeneca: 2009-2011 

Ensayo abierto de grupos paralelos para evaluar el impacto 

de la insulina inhalada (EXUBERA), en el control glucémico 

de pacientes ambulatorios con Diabetes Mellitus Tipo II 

poco controlados con dos antidiabéticos orales, durante 

seis meses. A2171121. Phase II 

Pfizer: 2008-2011 

PhD theses 

Metabolismo lipídico e hidrocarbonado en la obesidad 

mórbida. Efecto de la cirugía bariátrica 

Author: Sara García Serrano 

Thesis advisors: Federico Soriguer Escofet, Eduardo García 

Fuentes 

University: Universidad de Málaga 

Thesis defense date: June 25, 2010 ■ 

RT-PCR rotors ready for work. 

84 CibeRdem

Pharmacological targets in inflammation and 

metabolic diseases 

Unitat de Farmacologia, Facultat de Farmàcia, Universitat de Barcelona 

www.ub.edu 

Principal Investigator Manuel Vázquez Carrera mvazquezcarrera@ub.edu Postdoctoral fellow Xavier Palomer PhD students Lucía 

Serrano Marco, Emma Barroso, Laia Salvadó, Eva Capdevila Lab technician David Álvarez Guardia 








Keywords 

Insulin sensitivity and resistance. Lipid metabolism. Cardiac 

complications. Lipids, lipoproteins. Transcription factors. PPAR. 


A study of the molecular mechanisms involved in the link 

between inflammation and insulin resistance: 

a) evaluating the molecular mechanisms by which PPAR 

agonists prevent inflammation and insulin resistance, 

b) studying how monounsaturated fatty acids prevent 

saturated fatty-acid-induced insulin resistance, 

c) evaluating the mechanisms through which PPAR agonists 

may prevent the development of metabolic syndrome, 

dyslipidaemia and cardiac hypertrophy. 

Publications* 


Activation of peroxisome proliferator-activated receptor- 

{delta} by GW501516 prevents fatty acid-induced nuclear 

factor-{kappa}B activation and insulin resistance in skeletal 

muscle cells 

Coll T, Alvarez-Guardia D, Barroso E, Gómez-Foix AM, 

Palomer X, Laguna JC, Vázquez-Carrera M 


IF: 5.801 first quartile. With other CIBERDEM groups: AM 

Gómez Foix 

Cyclooxygenase 2 inhibition exacerbates palmitate-induced 

inflammation and insulin resistance in skeletal muscle cells 

Coll T, Palomer X, Blanco-Vaca F, Escolà-Gil JC, Sánchez 




85

RM, Laguna JC, Vázquez-Carrera M 


IF: 4.752 first quartile. With other CIBERDEM groups: F Blanco Vaca 

Disodium ascorbyl phytostanol phosphate (FM-VP4), a modified 

phytostanol, is a highly active hypocholesterolaemic agent 

that affects the enterohepatic circulation of both cholesterol 

and bile acids in mice 

Méndez-González J, Süren-Castillo S, Calpe-Berdiel L, 

Rotllan N, Vázquez-Carrera M, Escolà-Gil JC, Blanco-Vaca F 


IF: 3.446 first quartile. With other CIBERDEM groups: F Blanco Vaca 

The p65 subunit of NF-kappaB binds to PGC-1alpha, linking 

inflammation and metabolic disturbances in cardiac cells 

Alvarez-Guardia D, Palomer X, Coll T, Davidson MM, Chan 

TO, Feldman AM, Laguna JC, Vázquez-Carrera M 

Cardiovasc Res, 87, 449-458 (2010) 






CIBERDEM groups: M Vázquez Carrera, F Blanco Vaca, 

R Carmena, X Correig, L Masana 






CIBERDEM groups: M Vázquez Carrera, J Vendrell, 

A Zorzano, J Balsinde, AM Gómez Foix, S Fernández Veledo, 

E Montanya, R Simó ■ 

Book chapter 

Book: Research Advances in Endocrinology, Global 

Research Network, Kerala, India (2010) 

Chapter: New advances in inflammation and fatty acidinduced 

insulin resistance in skeletal muscle cells 

Authors: Coll T, Barroso E, Serrano L, Álvarez Guardia D, 

Salvadó L, Merlos M, Palomar X, Vázquez Carrera M 

Pages: 1-17 



Vías moleculares que conectan la inflamación con la 

resistencia a la insulina y la hipertrofia cardíaca. Estudio de 

los efectos de los ligandos de PPAR-beta/delta, el ácido oleico 

y las estatinas en modelos celulares y animales de resistencia 

a la insulina, síndrome metabólico e hipertrofia cardíaca 

MICINN, SAF2009-06939: 2009-2011 

Principal Investigator: Manuel Vázquez Carrera 

Adipocytes. 

86 CibeRdem

Diabetes and Metabolic Associated Diseases 

Research Group 

Hospital Universitari de Tarragona Joan XXIII, Institut d’Investigació Sanitària Pere Virgili 

www.iispv.cat 

Principal Investigator Joan J Vendrell jvo@comt.es Associate researchers Luís Gallart, Cristina Gutiérrez, Ana Megía, Matilde Rodríguez, 

Inmaculada Simón Postdoctoral fellows Xavier Escoté, Lourdes Garrido, Mercedes Miranda Research assistant María Victoria Ceperuelo 

Lab technicians Miriam Campos, Francesc Xavier Duran, Elsa Maymó, Gisela Pachón 












PhD theses: 1 

Awards: 1 

Keywords 

Insulin sensitivity and resistance. Metabolic syndrome. 

Prediction/prevention of type 2 diabetes. Pregnancy. Weight 

regulation and obesity. 


-Inflammatory mechanisms in type 2 diabetes and insulin 

resistance (chronic activation of the immune system). 

-Genetic susceptibility markers in diabetes (genetic and 

environmental interaction in diabetes). 

-Adipose cell biology - regulatory mechanisms of different 

adipose tissue cell types. Mesenchymal stem-cell biology 

(genes involved in adipose cell differentiation - paracrine/ 

endocrine analysis of adipose tissue inflammatory 

mechanisms in obesity and diabetes). 

Publications* 


Circulating bactericidal/permeability-increasing protein 

(BPI) is associated with serum lipids and endothelial 

function 

Esteve E, Castro A, Moreno JM, Vendrell J, Ricart W, 

Fernández-Real JM 




87

Thromb Haemost, 103, 780-787 (2010) 


Cyclin G2 regulates adipogenesis through PPAR gamma 

coactivation 

Aguilar V, Annicotte JS, Escote X, Vendrell J, Langin D, Fajas L 



Lpin1 in human visceral and subcutaneous adipose tissue: 

similar levels but different associations with lipogenic and 

lipolytic genes 

Miranda M, Escoté X, Alcaide MJ, Solano E, Ceperuelo- 

Mallafré V, Hernández P, Wabitsch M, Vendrell J 



Obesity and insulin resistance-related changes in the 

expression of lipogenic and lipolytic genes in morbidly 

obese subjects 

Tinahones FJ, Garrido-Sanchez L, Miranda M, García- 

Almeida JM, Macias-Gonzalez M, Ceperuelo V, Gluckmann 

E, Rivas-Marin J, Vendrell J, García-Fuentes E 



Paired subcutaneous and visceral adipose tissue 

aquaporin-7 expression in human obesity and type 2 

diabetes: differences and similarities between depots 

Miranda M, Escoté X, Ceperuelo-Mallafré V, Alcaide MJ, 

Simón I, Vilarrasa N, Wabitsch M, Vendrell J 



other CIBERDEM groups: E Montanya 

PP2A regulatory subunit PP2A-B’ counteracts S6K 

phosphorylation 

Hahn K, Miranda M, Francis VA, Vendrell J, Zorzano A, 

Teleman AA 



other CIBERDEM groups: A Zorzano 

Relation between human LPIN1, hypoxia and endoplasmic 

reticulum stress genes in subcutaneous and visceral 

adipose tissue 

Miranda M, Escoté X, Ceperuelo-Mallafré V, Megía A, 

Caubet E, Näf S, Gómez JM, González-Clemente JM, 

Vicente V, Vendrell J 



E Montanya 

The obese healthy paradox: is inflammation the answer? 

Barbarroja N, López-Pedrera R, Mayas MD, García-Fuentes 

E, Garrido-Sánchez L, Macías-González M, El Bekay R, 

Vidal-Puig A, Tinahones FJ 

Biochem J, 430, 141-149 (2010) 


Tumor necrosis-like weak inducer of apoptosis as a 

proinflammatory cytokine in human adipocyte cells: upregulation 

in severe obesity is mediated by inflammation 

but not hypoxia 

Vendrell J, Maymó-Masip E, Tinahones F, García-España A, 

Megia A, Caubet E, García-Fuentes E, Chacón MR 



Weight loss in prepubertal obese children is associated 

with a decrease in adipocyte fatty-acid-binding protein 

without changes in lipocalin-2: a 2-year longitudinal 

study 

Corripio R, Gónzalez-Clemente JM, Pérez-Sánchez J, Näf 

S, Gallart L, Nosàs R, Vendrell J, Caixàs A 

Eur J Endocrinol, 163, 887-893 (2010) 




Estudio del canal de glicerol (acuaporina 7) en la regulación 

coordinada del metabolismo del glicerol y de la glucosa 

en tejido adiposo abdominal humano. Disfunción en la 

obesidad y en la diabetes tipo 2 

Instituto de Salud Carlos III, FIS, 07/1024: 2008-2010 

Principal Investigator: Joan Vendrell Ortega 

Associate investigator: Cristina Gutiérrez 

Estudio de la regulación del gen LPIN1 en pacientes con 

obesidad y diabetes mellitus tipo 2. Análisis in vitro en 

adipocitos humanos de su respuesta a diferentes estímulos 

lipolíticos 

Instituto de Salud Carlos III, FIS, 08/1195: 2009-2011 


Estudio del efecto de la citocina TWEAK en la insulino 

resistencia del adipocito. Relación de la fracción soluble 

y de su expresión génica con marcadores inflamatorios en 

pacientes obesos con diabetes tipo 2 y con diferente grado 

de insulino resistencia 

Instituto de Salud Carlos III, FIS, 08/0733: 2009-2011 

Principal Investigator: Matilde Rodríguez Chacón 

Associate investigators: M Victoria Ceperuelo, Ana Megía 

Papel de las isoformas circulantes de adiponectina en 

la diabetes gestacional. Relación con el metabolismo 

hidrocarbonado y el desarrollo antropométrico fetal 

Instituto de Salud Carlos III, FIS, 09/2152: 2010-2012 

Principal Investigator: Inmaculada Simón Muela 

Associate investigator: Ana Megía 

88 CibeRdem


Grup de recerca en diabetis i co-morbiditats associades. 

DiReCor 

Generalitat de Catalunya, AGAUR, 2009 SGR 01257: 2009- 

2013 


Associate investigators: Miriam Campos, Victoria 

Ceperuelo, Xavier Escoté, Luís Gallart, Cristina Gutiérrez, 

Elsa Maymó, Ana Megía, Mercedes Miranda, Matilde 

Rodríguez, Inmaculada Simón 

Private funds 

El papel de la citoquina TWEAK en la diabetes gestacional 

y su relación con otras adipoquinas y la sensibilidad a la 

insulina 

Novo Nordisk: 2009-2011 


Associate investigators: Xavier Escoté, Ana Megía, 

Inmaculada Simón 

PhD theses 

Estudio del canal de glicerol AQP7 y de la adipoquina ZAG 

en el ámbito de la obesidad, la diabetes tipo 2 y el síndrome 

metabólico. Dos proteínas implicadas en la lipólisis del 

tejido adiposo 

Author: Victoria Ceperuelo Mallafré 

Thesis advisor: Joan Vendrell Ortega 


Thesis defense date: May 14, 2010 

Awards 

Award for a short term fellowship to visit the Montpellier 

Cancer Research Institute, Montpellier, EMBO-European 

Molecular Biology Organization (2010) 

Awardee: Xavier Escoté ■ 

Biology of GLP1 in adipose tissue: Characterization of 

a new insulin-mediated adipose cell proliferation control 

factor and its implications in inflammation and diabetes 

Laboratorios MSD: 2008-2010 








CIBERDEM groups: J Vendrell, S Fernández Veledo, 

A Zorzano, J Balsinde, AM Gómez Foix, E Montanya, R 

Simó, M Vázquez Carrera 






CIBERDEM groups: J Vendrell, X Correig, E Montanya, 

HF Escobar Morreale, R Simó 




CIBERDEM groups: J Vendrell, F Soriguer, R Carmena, 

L Castaño, R Gomis, M Serrano Ríos 



CIBERDEM Biobank Nodes: J Vendrell, R Gomis, A Novials, 

L Masana, L Castaño, M Serrano Ríos, F Soriguer, R Carmena, 

M Blanco Vaca 

Immunostaining in Caco-2 polarized cells. Differentiated Caco-2 

cells were immunostained with several organelle markers: A, Golgi 

(GM130); B, ER (calreticulin); C, F-actin (phalloidin) and D, tight 

junctions (ZO-1). 


89

Area 3 

Islet dysfunction, destruction and regeneration 

Autoimmunity 

Impact on the pathogenesis of diabetes 











Patents: 4 

PhD theses: 8

Area 3 of CIBERDEM comprises thirteen groups focused on developing new tools and knowledge for the molecular 

diagnosis of beta-cell function and for the cell and gene therapy of diabetes. 

Research initiated in previous years led to a remarkable number of articles, reviews and editorials (45), books and book 

chapters being published in 2010 in renowned publications including outstanding medical journals. Basic research into 

molecular mechanisms in metabolism, physiology and signalling in beta cells demonstrated the important role of key 

molecules such as GLP-1, ANP/ GC-A system, glucocorticoids, TH, PKCdelta, SOCS2, IRS2, TMEM2, and BACE2, which 

resulted in 19 publications. Cell- and gene-therapy approaches to recover beta-cell mass is an emerging field and novel 

findings involving mesenchymal stem cells, embryonic stem cells and bone marrow cells were reported in 6 articles. 

In addition, studies with human islet samples resulted in significant advances in knowledge about epigenic regulation 

of beta cells (open chromatin map) and the characterization of TMEM27 as a potential biomarker of beta-cell mass. 

Human genetic studies were also conducted this year and results involving mutations in GCK, SUR1, KIR6.2 and INS 

genes were reported. Furthermore, an in vivo strategy to study combinatorial gene regulation revealed how HNF1alpha 

and HNF4alpha control a common islet-cell regulatory programme which is defective in human monogenic diabetes. In 

addition to basic research, Area 3 has a strong focus on human clinical studies. In this regard, 21 clinical trials (phases I, 

II, III and IV) took place during 2010. 

A total of 8 PhD theses were defended, and 4 patents were applied for. It is worthy of note that 12 of the 45 total 

publications were in collaboration with other CIBERDEM groups, and 5 with other CIBERs. This demonstrates the good 

understanding between CIBERDEM and other CIBER groups. 

In summary, the activities conducted during 2010 proved very successful and resulted in key developments in the betacell 

field. 

Fàtima Bosch 



91

Endocrinology and metabolism 

Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, Universidad Complutense de Madrid 

www.ucm.es/info/biomol2 

Principal Investigator Carmen Álvarez calvarez@farm.ucm.es Associate researchers Fernando Escrivá, María Ángeles Martín 

Postdoctoral fellow Elisa Fernández PhD student Juan de Toro Lab technician Esther Lizárraga 


Publications: 2, 1 in the first quartile and 1 in the second quartile 







PhD theses: 1 

Keywords 

Islet degeneration and damage. Beta-cell signal transduction. 

Insulin action. Insulin sensitivity and resistance. Gastroentero 

pancreatic factors. 


The identification of the cellular and molecular mechanisms 

that link poor perinatal growth and increased risk of obesity 

and type 2 diabetes in adult life through the use of animal 

models of nutritional manipulation: maternal undernutrition 

followed or not by overnutrition, focused on: 

a) the effects of nutrients on the development, growth 

and death of pancreatic islet-cells and the implication 

of the IGFs. 

b) insulin/glucagon signalling pathways in both peripheral 

and central tissues: liver, cortex and hypothalamus. 

c) the possible alterations of hypothalamic response to 

leptin associated with under/overnutrition. 

d) the potential role of incretins in the relationship between 

intrauterine growth restriction and the development of 

glucose intolerance. 

Publications* 


Maternal undernutrition increases pancreatic IGF-2 and 

partially suppresses the physiological wave of {beta}-cell 

apoptosis during the neonatal period 

de Miguel-Santos L, Fernández-Millán E, Angeles Martín M, 



92 CibeRdem

Escrivá F, Alvarez C 

J Mol Endocrinol, 44, 25-36 (2010) 


PTP1B deficiency enhances liver growth during suckling by 

increasing the expression of insulin-like growth factor-I 

Escrivá F, González-Rodriguez A, Fernández-Millán E, 

Rondinone CM, Alvarez C, Valverde AM 



other CIBERDEM groups: A Martínez Valverde 



Mecanismos moleculares que regulan el crecimiento y 

muerte de las células beta pancreáticas y las acciones 

insulínicas en el SNC: estudio en ratas subnutridas y 

diabéticas 

Ministerio de Ciencia e Innovación, BFU 2008-02930: 

2009-2011 

Principal Investigator: Carmen Álvarez 

Programming of beta cell mass homeostasis in diabetes. 

Relationship with pancreatic IGFs 

Ministerio de Ciencia e Innovación, HF2007-0076: 


Principal Investigator: Carmen Álvarez 

Coordinator: Bernard Portha 

Comunidad Autónoma de Madrid, CCG07-UCM/SAL-3004: 


Principal Investigator: Fernando Escrivá 







CIBERDEM groups: C Álvarez, M Serrano Ríos, E Blázquez, 


PhD theses 

Implicación del sistema de IGFs en el desarrollo y 

crecimiento de las células beta pancreáticas en dos 

modelos de experimentación animal: subnutrición y 

diabetes 

Author: Laura de Miguel de Santos 

Thesis advisors: Carmen Álvarez Escolá, Elisa Fernández 

Millán 


Thesis defense date: October 9, 2010 ■ 


Mecanismos moleculares implicados en el desarrollo 

y crecimiento de las células beta pancreáticas y en 

las acciones de la insulina en el SNC: estudio en ratas 

subnutridas 

Periodic Acid Schiff (PAS) stain for liver glycogen detection in control (C) and undernourished (U) adult rats (x20). 


93

Brain glucose sensor, satiety control, insulin 

resistance and type 2 diabetes 

Universidad Complutense de Madrid 

www.ucm.es 

Principal Investigator Enrique Blázquez eblazquez@med.ucm.es Associate researchers Elvira Álvarez García, María Ángeles Navas 

Hernández, Isabel Roncero Rincón, Juan Miguel Ruiz Albusac, María del Carmen Sanz Miguel, Esther Velázquez Sánchez PhD students 

Carmen García Herrero, Verónica Hurtado Carneiro Lab manager Pedro Alberto Barrio Lab technicians Alberto Crespo, Laura del Barrio 

Diez, Ana María de Lucas Cerrillo 









Keywords 

Genetics type 2 diabetes. Hormone receptors. Incretins. 

Stem cells. Weight regulation and obesity. 


-Modifications of cerebral glucose metabolism in 

pathophysiological states related to feeding behaviour. 

-The effects of GLP-1 and GLP-2 on the expression and activity 

of hypothalamic metabolic sensors and characterization of 

the neuroprotective role of these peptides. 

-The effect of GLP-2 on the proliferation of cultured rat 

astrocytes. 

-Signalling and the biological effects of GLP-1 on 

mesenchymal stem cells of human bone marrow and mouse 

embryonic stem cells - its effect on cell differentiation. 

-Molecular diagnosis of monogenic diabetes (MODY) and 

the functional characterization of MODY mutations. 

Publications* 


Signaling and biological effects of glucagon-like peptide 

1 on the differentiation of mesenchymal stem cells from 

human bone marrow 

Sanz C, Vázquez P, Blázquez C, Barrio PA, Alvarez M del 

M, Blázquez E 



94 CibeRdem


IF: 4.395 first quartile. With other CIBERDEM groups: Flora 

de Pablo 



Efectos de los péptidos semejantes al glucagon GLP-1 

y GLP-2 y otros péptidos anorexigénicos y orexigénicos 

sobre el metabolismo de la glucosa y el contenido de 

serotonina y su relector 1A en cerebro de rata 


2009-2012 

Principal Investigator: Enrique Blázquez 

Associate investigators: M del Carmen Sanz Miguel, José Antonio 

Zueco Alegre, Luís García García, Pedro A Barrio Caballero 


Estudio funcional de mutaciones en los factores de 

transcripción HNF-1A y HNF-1B asociados a diabetes 

monogénica 

UCM-Comunidad Autónoma de Madrid, CCG08-UCM/SAL- 

3623: 2009-2010 

Principal Investigator: María Ángeles Navas 

Associate investigator: CM García Herrero 

Programa de Creación y Consolidación de Grupos de 

Investigación Universidad Complutense-Comunidad 

Autónoma de Madrid al Grupo «Sensores cerebrales de 

glucosa, control de la saciedad, obesidad y diabetes tipo 2» 

UCM-Santander, GR58/08: 2009-2010 

Principal Investigator: Elvira Álvarez 

Associate investigators: E Blázquez, I Roncero, MC Sanz, 

E Velázquez, JM Ruiz, JA Zueco, MA Navas, MC García 

Herrero 

Private funds 

Papel de péptidos anorexigénicos sobre el metabolismo 

cerebral de glucosa y del receptor IA de serotonina en 

pacientes con anorexia y bulimia nerviosa u obesidad por 

atracón 

Fundación Médica Mutua Madrileña: 2007-2010 

Principal Investigator: Enrique Blázquez 

Associate investigators: E Álvarez, I Roncero, JI Ulibarri, S 

Bescos, JE García Camba, MA Pozo 

Representative scheme of GLP-1 effects. 


95

Caracterización del mecanismo neuroprotector de GLP-1 y 

GLP-2 en cerebro. Potencial aplicación de estos péptidos 

en enfermedades neurodegenerativas 

Fundación Médica Mutua Madrileña: 2008-2011 

Principal Investigator: Elvira Álvarez 

Associate investigators: E Blázquez, I Roncero, MC Sanz, E 

Velázquez, JM Ruiz, JA Zueco 







CIBERDEM groups: E Blázquez, C Álvarez, M Serrano Ríos, 



monogenic diabetes: from the bench to the bedside 

MODIAB: 2009-2010 

Coordinator: Luis Castaño 

CIBERDEM groups: E Blázquez, L Castaño, J Ferrer, 

M Vallejo ■ 

96 CibeRdem

Transgenic animal models and gene therapy 

approaches for diabetes 

Centre de Biotecnologia Animal i Teràpia Gènica, Universitat Autònoma de Barcelona 

http://cbateg.uab.cat 

Principal Investigator Fàtima Bosch fatima.bosch@uab.cat Associate researchers Ana Carretero, Tura Ferré, Sylvie Franckhauser, Miquel 

García, Xavier Leon, Maria Molas, Sergio Antonio Muñoz, Víctor Nacher, Marc Navarro, Pedro José Otaegui, Anna Pujol, Martí Pumarola, 

Efren Riu, Jesús Ruberte, Virginia Haurigot Postdoctoral fellows Eduard Ayuso, Alba Casellas, Judith Agudo, Laia Vilà, Mercè Obach, 

Ricardo Lage PhD students David Callejas, Ivet Elias, Verónica Jiménez, Albert Ribera, Carles Roca, Albert Ruzo, Pilar Villacampa, 

Meritxell Morró Lab technicians Jennifer Barrero, Marta Moya, Mireia Zaguirre Administrative staff Montse Bellido 









Patents: 2 

PhD theses: 1 

Keywords 

Beta-cell signal transduction. Gene therapy. Insulin 

sensitivity and resistance. Neuropathy-somatic. 

Retinopathy. 


-The study of the causes and pathophysiological 

mechanisms of diabetes mellitus using transgenic animal 

models. 

-Analysis of the role of metabolic pathways in the 

development of insulin resistance and obesity, and 

the investigation of the molecular mechanisms 

involved in secondary complications (retinopathy, 

neuropathy). 

-The development of new gene-therapy approaches for the 

treatment of diabetes mellitus based: 

a) on the manipulation of skeletal muscle and the liver to 

increase glucose uptake, and 

b) on engineering the endocrine pancreas in vivo to 

regenerate beta cell mass. 


97

Publications* 


Chronically increased glucose uptake by adipose tissue 

leads to lactate production and improved insulin sensitivity 

rather than obesity in the mouse 

Muñoz S, Franckhauser S, Elias I, Ferré T, Hidalgo A, 

Monteys AM, Molas M, Cerdán S, Pujol A, 

Ruberte J, Bosch F 



Deficiency of CB2 cannabinoid receptor in mice improves 

insulin sensitivity but increases food intake and obesity 

with age 

Agudo J, Martin M, Roca C, Molas M, Bura AS, Zimmer A, 

Bosch F, Maldonado R 



Diabetic neuropathy: electrophysiological and morphological 

study of peripheral nerve degeneration and regeneration in 

transgenic mice that express IFNbeta in beta cells 

Serafín A, Molín J, Márquez M, Blasco E, Vidal E, 

Foradada L, Añor S, Rabanal RM, Fondevila D, Bosch F, 

Pumarola M 

Muscle Nerve, 41, 630-641 (2010) 


High AAV vector purity results in serotype- and tissueindependent 

enhancement of transduction efficiency 

Ayuso E, Mingozzi F, Montane J, Leon X, Anguela XM, Haurigot 

V, Edmonson SA, Africa L, Zhou S, High KA, Bosch F, Wright JF 

Gene Ther, 17, 503-510 (2010) 


Hypothalamic-specific manipulation of Fto, the ortholog of 

the human obesity gene FTO, affects food intake in rats 

Tung YC, Ayuso E, Shan X, Bosch F, O’Rahilly S, Coll AP, Yeo 

GS 



Overexpression of kinase-negative protein kinase Cdelta 

in pancreatic beta-cells protects mice from diet-induced 

glucose intolerance and beta-cell dysfunction 

Hennige AM, Ranta F, Heinzelmann I, Düfer M, Michael 

D, Braumüller H, Lutz SZ, Lammers R, Drews G, Bosch F, 

Häring HU, Ullrich S 



The suppressor of cytokine signalling 2 (SOCS2) is a key 

repressor of insulin secretion 

Lebrun P, Cognard E, Gontard P, Bellon-Paul R, Filloux C, 

Berthault MF, Magnan C, Ruberte J, Luppo M, Pujol A, 

Pachera N, Herchuelz A, Bosch F, Van Obberghen E 



Reviews 

Production, purification and characterization of adenoassociated 

vectors 

Representative laser-scanning confocal images in isolated adipocytes from transgenic mice aP2-GK. Co-localization (c, merged) of 

glucokinase (GK) (a) with mitochondria (b). GK was marked with green fluorescent Alexa 488 and mitochondria with orange rosamine 

mitotracker. Nuclei of adipocytes were marked with blue Hoechst stain solution. Note that GK and mitochondria surround an empty space 

corresponding to the unilocular lipid droplet. Scale bar, 11 µm. Image from: Diabetologia, 2010. 



98 CibeRdem

Ayuso E, Mingozzi F, Bosch F 

Curr Gene Ther, 10, 423-436 (2010) 


Skeletal muscle metabolism in the pathology and treatment 

of type 1 diabetes 

Mann CJ, Ayuso E, Anguela XM, Bosch F 

Curr Pharm Des, 16, 1002-1020 (2010) 




Identification of the genes regulated by the SIRT1 histone 

deacetylase and their contribution in the pathogenesis of 

type 2 diabetes and obesity 

EU, Marie Curie International Reintegration Grant, MIRG- 

CT-2007-207745: 2008-2012 

Principal Investigator: Efrén Riu 

Analysis of a new pathway to import iron into the retina: 

role of ferritin as iron carrier and implications in radical 

detoxification 

FCT Fundaçao para a ciência e a tecnologia. Ministério da 

ciência, tecnologia e ensino superior 

Portugal, PTDC/SAU-ORG/110856/2009: 2010-2012 

Principal Investigator: Jesús Ruberte 

INFRAFRONTIER. The European Infrastructure for 

phenotyping, archiving and dissemination of disease 

models 

EU, European Strategy Forum on Research Infrastructures, 

FP7-INFRA-STRUCTURES-2007-1: 2008-2012 

Principal Investigator: Fàtima Bosch 

Coordinator: Martin Hrabé d’Angelis 

EUMODIC. The European Mouse Disease Clinic. A distributed 

phenotyping resource for studying human disease 

EU, Integrated Project FP6-2005-LIFESCIHEALTH-6, LSHG- 

CT-2006-037188: 2007-2011 


Coordinator: Steve Brown 

CLINIGENE. European Network for the Advancement of 

Clinical Gene Transfer and Therapy 

EU, Network of Excellence, FP6-2004-LIFESCIHEALTH-5, 

LSHB-CT-2006-018933: 2006-2011 


Coordinator: Odile Cohen-Haguenauer 


Estudio del papel de los leucotrienos en el desarrollo de 

la resistencia a la insulina y aterosclerosis asociadas a la 

obesidad 


Principal Investigator: Sylvie Franckhauser 

Neuropatía Diabética: estudio de la expresión génica en 

la degeneración y posterior regeneración nerviosa en un 

modelo murino transgénico RIP/IFNbeta 

Ministerio de Educación y Ciencia, PI 05/0892: 2008-2010 

Principal Investigator: Martí Pumarola 

Atlas morfológico para el fenotipado de ratones mutantes 

Ministerio de Ciencia e Innovación, SAF2008-0581-E: 

2009-2011 


Estudio del efecto de la deacetilación de cromatina por 

miembros de la familia de las sirtuinas en la patogénesis 

de la resistencia a la insulina y diabetes tipo 2 

Ministerio de Ciencia e Innovación, SAF2008- 03083: 2009-2011 

Principal Investigator: Efrén Riu 

Estudio del papel de los factores de crecimiento similares 

a la insulina en la regeneracion de la celula ß pancreática 

Ministerio de Educación y Ciencia, SAF2008-00962: 

2009-2011 


Desarrollo de vectores adeno-asociados (AAV) para la 

terapia neuroprotectora en enfermedades degenerativas 

de la retina 

Proyectos TRACER, Ministerio de Ciencia e Innovación 

en colaboración con ProRetina Therapeutics SL, 

PET2008_0282_02: 2009-2011 

Principal Investigators: Enrique de la Rosa, Fàtima Bosch 

With other CIBERs: CIBERER 

Senescencia celular en los vasos sanguíneos de 

la retina: implicaciones de P16 en el cross-linking 

enzimático del colágeno de la membrana basal durante 

el envejecimiento 



Generación de una librería AAV-CRE para la obtención de 

ratones mutantes condicionales 

Ministerio de Educación y Ciencia, SAF2010-10507-E: 




Ajut per a grups de recerca consolidats 

Agència de Gestió d´Ajuts Universitaris i de Recerca 

(AGAUR), Generalitat de Catalunya, SGR 224: 2009-2013 


Patents 

European patents 

Telomerase reverse transcriptase for protection against 

ageing 


99




Inventors: M Antonia Blasco, Bruno Bernardes, Fàtima 

Bosch, Eduard Ayuso 

Universitat Autònoma de Barcelona and Centro Nacional 

de Investigaciones Oncológicas 

Gene Therapy composition for use in diabetes treatment 




Inventors: Fàtima Bosch, Eduard Ayuso, David Callejas 

Universitat Autònoma de Barcelona 

PhD theses 

A study of the role of VEGF overexpression in adipose 

tissue in diet-induced obesity and insulin resistance 

Author: Ivet Elias Puigdomènech 

Thesis advisors: Fàtima Bosch, Sylvie Franckhauser 

University: Universitat Autònoma de Barcelona 

Thesis defense date: December 15, 2010 ■ 

100 CibeRdem

Laboratory of Molecular Endocrinology 

Centro de Investigación Príncipe Felipe, Valencia 

www.cipf.es 

Principal Investigator Deborah Burks dburks@cipf.es Postdoctoral fellows Silvia Sanz, Carlos Acosta, Luke Noon, Ana Sánchez 

PhD students Juan Martin, Verónica Moreno Lab manager Lorena Menes 


Publications: 3, in the first decile 








PhD theses: 1 

Keywords 

Beta-cell signal transduction. Insulin sensitivity and 

resistance. Islet degeneration and damage. Retinopathy. 

Obesity. Stem cells. 


-Regulation of the cell-cycle in pancreatic beta cells. 

-The role of IRS-2 signals in the differentiation of human 

embryonic stem cells to endoderm lineages. 

-IRS-2 signalling in the regulation of neuronal function. 

-The role of insulin/IGF-I signalling in diabetic retinopathy. 

Publications* 


Bisphenol A exposure during pregnancy disrupts 

glucose homeostasis in mothers and adult male 

offspring 

Alonso-Magdalena P, Vieira E, Soriano S, Menes L, Burks D, 

Quesada I, Nadal A 

Environ Health Perspect, 118, 1243-1250 (2010) 

IF: 6.191 first decile. With other CIBERDEM groups: A Nadal 

Inhibition of PTP1B restores IRS1-mediated hepatic insulin 

signaling in IRS2-deficient mice 

González-Rodríguez A, Mas Gutierrez JA, Sanz-González 

S, Ros M, Burks DJ, Valverde AM 





101

IF: 8.505 first decile. With other CIBERDEM groups: 

A Martínez Valverde 

Hypoxia promotes efficient differentiation of human 

embryonic stem cells to functional endothelium 

Prado-Lopez S, Conesa A, Armiñán A, Martínez-Losa 

M, Escobedo-Lucea C, Gandia C, Tarazona S, Melguizo 

D, Blesa D, Montaner D, Sanz-González S, Sepúlveda 

P, Götz S, O’Connor JE, Moreno R, Dopazo J, Burks DJ, 

Stojkovic M 

Stem Cells, 28, 407-418 (2010) 


other CIBERs: CIBERNED 


CIBERDEM groups: D Burks, M Benito, R Gomis 

PhD theses 

La regulación de la expresión de IRS-2 en el sistema 

nervioso 

Author: María Jesús García Belda 

Thesis advisor: Deborah Burks 

University: Universidad de Valencia 

Thesis defense date: September 24, 2010 ■ 



LIV-ES: Development of culture conditions for the 

differentiation of hES cells to hepatocytes 

European Commission, Seventh Framework Programme, 

FP7-HEALTH-2007-B: 2008-2011 

Principal Investigator: Deborah Burks 

Coordinator: Anne Weber 


Análisis de la vía de señalización insulina/IRS-2 como un link 

molecular entre metabolismo diabético y neurodegeneración 


2008-2011 


El papel de IRS-2 en la regeneración del páncreas endocrino 

Instituto de Salud Carlos III, Programa de Estabilización del 

Grupos EMER07/012: 2007-2012 








CIBERDEM groups: D Burks, A Martínez Valverde, R Simó 






CIBERDEM groups: D Burks, C Álvarez, E Blázquez, M Serrano 

Ríos, M Vallejo 





IRS2-mediated GFP expression in developing human hepatocytes. 

102 CibeRdem

Hospital de Cruces Diabetes Research Group 

Hospital de Cruces, Barakaldo 

www.hospitalcruces.com 

Principal Investigator Luis Castaño lcastano@osakidetza.net Associate researchers María Ángeles Aniel Quiroga, Jose Ramon Bilbao, 

María Ángeles Busturia, Alicia Cortázar, Sonia Gaztambide, Itxaso Rica, Federico Vázquez, Amaia Vela Postdoctoral fellows Rosa María 

Martínez, Miriam Ramírez Research assistant Inés María Urrutia PhD students Anibal Aguayo, Oihana Belar, Ainara Castellanos, Javier 

de las Heras, Teba González, Tamara López, Leticia Plaza, Nora Fernández Lab managers Galder Gutiérrez, Gustavo Pérez de Nanclares 

Nurse Alicia Cobo Nutritionist Ana María Megido Administrative staff Sorkunde Rivero 

Total IF: 116.098 

Publications: 6, 4 of them in the first decile and 2 in the second quartile 










PhD theses: 1 

Awards: 2 

Keywords 

Clinical diabetes. Genetics type 1 diabetes. Monogenic 

diabetes. Oral pharmacological agents. Prediction/ 

prevention of type 1 diabetes. 


-The identification of additional genetic susceptibility 

markers for type 1 diabetes and related autoimmune 

disorders in the extended MHC (6p21) and other regions 

using high throughput genotyping. 

-The study of immune mediators of disease 

development, characterization of novel autoantigens/ 

antibodies and cell populations in patients: Th1, Th2 

and Th17 responses. 

-The identification of new genes responsible for monogenic 

diabetes by genome wide analysis (both CGI and CGH 

approaches). 

-The molecular and clinical characterization of monogenic 


103

diabetes and new therapeutic strategies for KATP channel 

alterations. 

-The prediction and prevention of type 1 diabetes. 

-The control of diabetes complications. 

-The epidemiology of diabetes. 

Publications* 


Effect of nateglinide on the incidence of diabetes and 

cardiovascular events 

NAVIGATOR Study Group, Holman RR, Haffner SM, 

McMurray JJ, Bethel MA, Holzhauer B, Hua TA, Belenkov 

Y, Boolell M, Buse JB, Buckley BM, Chacra AR, Chiang FT, 

Charbonnel B, Chow CC, Davies MJ, Deedwania P, Diem P, 

Einhorn D, Fonseca V, Fulcher GR, Gaciong Z, Gaztambide 

S, Giles T, Horton E, Ilkova H, Jenssen T, Kahn SE, Krum 

H, Laakso M, Leiter LA, Levitt NS, Mareev V, Martinez F, 

Masson C, Mazzone T, Meaney E, Nesto R, Pan C, Prager 

R, Raptis SA, Rutten GE, Sandstroem H, Schaper F, Scheen 

A, Schmitz O, Sinay I, Soska V, Stender S, Tamás G, Tognoni 

G, Tuomilehto J, Villamil AS, Vozár J, Califf RM 

N Engl J Med, 362, 1463-1476 (2010) 


Effect of valsartan on the incidence of diabetes and 

cardiovascular events 

NAVIGATOR Study Group, McMurray JJ, Holman RR, 

Haffner SM, Bethel MA, Holzhauer B, Hua TA, Belenkov Y, 

Boolell M, Buse JB, Buckley BM, Chacra AR, Chiang FT, 

Charbonnel B, Chow CC, Davies MJ, Deedwania P, Diem P, 

Einhorn D, Fonseca V, Fulcher GR, Gaciong Z, Gaztambide 

S, Giles T, Horton E, Ilkova H, Jenssen T, Kahn SE, Krum 

H, Laakso M, Leiter LA, Levitt NS, Mareev V, Martinez F, 

Masson C, Mazzone T, Meaney E, Nesto R, Pan C, Prager 

R, Raptis SA, Rutten GE, Sandstroem H, Schaper F, Scheen 

A, Schmitz O, Sinay I, Soska V, Stender S, Tamás G, Tognoni 

G, Tuomilehto J, Villamil AS, Vozár J, Califf RM 



Recessive mutations in the INS gene result in neonatal 

diabetes through reduced insulin biosynthesis 

Garin I, Edghill EL, Akerman I, Rubio-Cabezas O, Rica I, 

Locke JM, Maestro MA, Alshaikh A, Bundak R, del Castillo 

G, Deeb A, Deiss D, Fernandez JM, Godbole K, Hussain K, 

O’Connell M, Klupa T, Kolouskova S, Mohsin F, Perlman K, 

Sumnik Z, Rial JM, Ugarte E, Vasanthi T; Neonatal Diabetes 

International Group, Johnstone K, Flanagan SE, Martínez 

R, Castaño C, Patch AM, Fernández-Rebollo E, Raile K, 

Morgan N, Harries LW, Castaño L, Ellard S, Ferrer J, Perez 

de Nanclares G, Hattersley AT 

Proc Natl Acad Sci U S A, 107, 3105-3110 (2010) 


other CIBERDEM groups: J Ferrer. With other CIBERs: 

CIBERER 

The first clinical case of a mutation at residue K185 of 

Kir6.2 (KCNJ11): a major ATP-binding residue 

Shimomura K, de Nanclares GP, Foutinou C, Caimari M, 

Castaño L, Ashcroft FM 

Diabet Med, 27, 225-229 (2010) 


Book chapters 

Book: Diagnóstico y tratamiento de las Enfermedades 

Metabólicas Hereditarias, Ed. Ergón (2010) 

Chapter: Hiperinsulinismo persistente en el neonato 

Authors: Castaño L, Pérez de Nanclares G, Vela A, Garin I 

Pages: 364-375 

Book: Tecnologías aplicadas a la diabetes, Sociedad 

Española de Diabetes (2010) 

Chapter: Retinografía con cámara de retina no midriática 

para el cribado de la retinopatía diabética 

Authors: Vázquez San Miguel F, Goñi Iriarte MJ, Martínez 

Alday N 

Pages: 103-124 

Heterozygous glucokinase mutations and birth weight in 

Spanish children 

de Las Heras J, Martínez R, Rica I, de Nanclares GP, Vela A, 

Castaño L; Spanish MODY Group 



Neonatal diabetes caused by mutations in sulfonylurea 

receptor 1: interplay between expression and Mg-nucleotide 

gating defects of ATP-sensitive potassium channels 

Zhou Q, Garin I, Castaño L, Argente J, Muñoz-Calvo MT, 

Perez de Nanclares G, Shyng SL 

J Clin Endocrinol Metab, 95, E473-478 (2010) 


other CIBERs: CIBEROBN 

Functional characterization of SUR1 mutations: 86 Rb + efflux profile 

from COS cells transiently expressing WT or mutant K ATP 

channel 

subunits. 



104 CibeRdem


International projects 

Trial to reduce IDDM in children at genetic risk. TRIGR 

National Institutes of Health, 5U01HD040364-08: 

2007-2011 

Principal Investigator: Castaño L 

Coordinator: Akerbloom H 

Associate investigators: Martul P, Bilbao JR, Rica I 

Centre Differences study in children aged under 11 years 

Hvidore Study Group on Childhood diabetes, Novo-Nordisk: 



Associate investigator: de Beaufort C 


Diabetes Neonatal y de comienzo precoz: Caracterización 

molecular y fenotipo 

Ministerio de Sanidad y Consumo-ISCIII, PS09/01492: 



Associate investigators: Fernández Ramos C, Busturia MA, Rica 

I, Martínez R, Rodríguez A, Blarduni E, Chueca M, Oyarzabal M 


Etiopatogenia de los trastornos autoinmunes: Diabetes 

mellitus tipo 1 y Enfermedad Celiaca 

Departamento de Educación - Gobierno Vasco, IT-472-07: 

2007-2012 


Associate investigators: Vitoria JC, Gaztambide S, Bilbao JR 

Epidemiología de la diabetes en el Pais Vasco 

Departamento de Sanidad y Consumo - Gobierno Vasco, 

2009COM11: 2009-2010 


Associate investigator: Gaztambide S 

Encapsulación de islotes pancreáticos de ratón: Análisis 

de la funcionalidad y revascularización in vitro e in vivo 

Departamento de Industria - Gobierno Vasco, SAIO09- 

PE09BF01: 2009-2010 


Associate investigators: Ramírez M, Vázquez F, Pérez de 

Nanclares G 






CIBERDEM groups: L Castaño, E Blázquez, J Ferrer, M Vallejo 




CIBERDEM groups: L Castaño, F Soriguer, R Carmena, 

R Gomis, M Serrano Ríos, J Vendrell 



CIBERDEM Biobank Nodes: L Castaño, R Gomis, A Novials, J 

Vendrell, L Masana, M Serrano Ríos, F Soriguer, R Carmena, F 

Blanco Vaca 


Estudio aleatorizado, controlado frente a placebo, doble 

ciego, paralelo y multicéntrico para evaluar antagonistas de 

IL-1 en sujetos con diabetes tipo 1 de reciente diagnóstico. 

AIDA. Phase II B 

Steno Diabetes Center, EudraCT 2007-007146-34: 2009-2010 

Name of the participants: Gaztambide S, Vázquez F, Moure 

MD, Moreno A, Gallego P 

Estudio multicéntrico, randomizado, abierto, doble ciego, 

con doble enmascaramiento, controlado frente a un 

comparador activo para evaluar eficacia, seguridad y 

tolerancia de taspoglutida comparado con pioglitazona 

en pacientes con diabetes mellitus tipo 2 controlados 

inadecuadamente con sulfonilurea (SU) en monoterapia o 

con la combinación metformina más sulfonilurea. Phase II B 

Hoffmann-La Roche, RO5073031: 2009-2010 

Name of the participants: Santamaría J, Cortázar A 

A phase III 3 arm randomized double-blind placebo 

controlled multicenter study to investigate the impact of 

Diamyd on the progression of diabetes in patients newly 

diagnosed with type 1 diabetes mellitus. Phase III 

Diamyd Therapeutics, D/P3/07/4: 2008-2010 

Name of the participants: Castaño L, Rica I 

European prescription survey of short acting insulin 

analogues in children and adolescents. EPIC Study. Phase III 

Sanofi-Aventis, DIREG_R_04154: 2008-2010 

Name of the participant: Castaño L (steering committee 

member) 

European postmarketing observational prospective cohort 

study of children with type 1 diabetes treated with apidra. 

OCAPI Study. Phase III 

Sanofi-Aventis, APIDR_C_03909: 2008-2010 

Name of the participant: Castaño L (steering committee 

member) 

Ensayo de fase 2, multicéntrico, en doble ciego, controlado 

con placebo, de grupos paralelos y aleatorizado para 

evaluar la eficacia hipoglucemiante, la seguridad renal, la 

farmacodicinética y la farmacodinámica de DAPAGLIFLOZIN 

en sujetos con diabetes mellitus tipo 2 e insuficiencia renal 

moderada con un inadecuado control glucémico. Phase II 


105

Bristol-Myers Squibb, CEIC 08/47: 2008-2010 

Name of the participants: Gaztambide S, Goikolea I 

PhD theses 

Functional players in coeliac disease: identification and 

genetic association 

Author: Ainara Castellanos Rubio 

Thesis advisors: Bilbao JR, Castaño L 

University: Universidad del Pais Vasco, European thesis 


Awards 

Premio a la Investigación en Endocrinologia Pediátrica y 

crecimiento (2010) 

Institution: Fundación de la Sociedad Española de 

Endocrinología Pediátrica 

Awardees: Castaño L, Bilbao JR 

Premio a la mejor Comunicación Básica (2010) 

Institution: XII Congreso de la Sociedad de Endocrinología, 

Diabetes y Nutrición de Euskadi 

Awardees: Ramírez Domínguez M, López Euba T, 

Castaño L ■ 

106 CibeRdem

Proinsulin and tyrosine hydroxilase in development 

and differentiation 

Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid 

www.cib.csic.es 

Principal Investigator Flora de Pablo fdepablo@cib.csic.es Associate researcher Catalina Hernández Postdoctoral fellow Patricia 

Vázquez Lab technician Cayetana Murillo 






Patents: 1 

Keywords 

Catecholamines. Hormone receptors. Proinsulin. Islet 

development. Insulin sensitivity and resistance. 


To characterize TH expression pattern in mouse pancreas 

development and the analysis of TH function by studying 

pancreatic cell markers in TH-/- developing mice. 

Publications* 


Signaling and biological effects of glucagon-like peptide 

1 on the differentiation of mesenchymal stem cells from 

human bone marrow 

Sanz C, Vázquez P, Blázquez C, Barrio PA, Alvarez M del 

M, Blázquez E 



E Blázquez 



Transcritos quimera y otras formas atípicas de regulación 

génica y sus implicaciones en el desarrollo temprano 

Ministerio de Ciencia e Innovación, BFU2007-61055: 2007-2010 

Principal Investigator: Flora de Pablo 

Patents 

National patent 

Uso de la proinsulina para la elaboración de una 

composición farmacéutica neuroprotectora, composición 




107

terapéutica que la contiene y sus aplicaciones 

Patent application number: ES2331342B1 

Inventors: EJ de la Rosa Cano, F de Pablo Dávila, P Boya 

Tremoleda, S Corrochano Sánchez, P de la Villa Polo, R 

Barhoum Tannous and F Bosch Tubert 

CIB-CSIC, Universitat Autònoma de Barcelona and 

Universidad de Alcalá de Henares (2010) ■ 

Effects of dopamine treatment on embryonic pancreas in organotypic 

culture. 

108 CibeRdem

Genomic programming of beta cells 

Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona 

www.betacellregulation.net 

Principal Investigator Jorge Ferrer jferrer@clinic.ub.es Postdoctoral fellows Ildem Akerman, Miguel Ángel Maestro, Lorenzo Pasquali, 

Santiago Rodríguez PhD students Ignasi Moran, Myriam Solar, Joris van Arensbergen, Nikolina Nakic, Miguel A Correa Lab manager 

Carme Sanahuja Lab technician Xavier Garcia, Vanesa Grau 











Keywords 

Genetics type 2 diabetes. Genomics. Islet development. 

Transcription factors. 


-Mouse genetic analysis of beta-cell regulation. 

-Understanding the epigenome of pancreatic beta cells 

and its implications for the development, plasticity and 

growth of beta cells. 

-The regeneration of pancreatic beta cells. 

Publications* 


A map of open chromatin in human pancreatic islets 

Gaulton KJ, Nammo T, Pasquali L, Simon JM, Giresi PG, 

Fogarty MP, Panhuis TM, Mieczkowski P, Secchi A, Bosco D, 

Berney T, Montanya E, Mohlke KL, Lieb JD, Ferrer J 

Nat Genet, 42, 255-259 (2010) 



Derepression of Polycomb targets during pancreatic 

organogenesis allows insulin-producing beta-cells to adopt 

a neural gene activity program 

van Arensbergen J, García-Hurtado J, Moran I, Maestro 




109

MA, Xu X, Van de Casteele M, Skoudy AL, Palassini M, 

Heimberg H, Ferrer J 

Genome Res, 20, 722-732 (2010) 


Epistasis of transcriptomes reveals synergism between 

transcriptional activators Hnf1alpha and Hnf4alpha 

Boj SF, Petrov D, Ferrer J 

PLoS Genet, 6, e1000970 (2010) 


Recessive mutations in the INS gene result in neonatal 

diabetes through reduced insulin biosynthesis 

Garin I, Edghill EL, Akerman I, Rubio-Cabezas O, Rica I, 

Locke JM, Maestro MA, Alshaikh A, Bundak R, del Castillo 

G, Deeb A, Deiss D, Fernandez JM, Godbole K, Hussain K, 

O’Connell M, Klupa T, Kolouskova S, Mohsin F, Perlman K, 

Sumnik Z, Rial JM, Ugarte E, Vasanthi T; Neonatal Diabetes 

International Group, Johnstone K, Flanagan SE, Martínez 

R, Castaño C, Patch AM, Fernández-Rebollo E, Raile K, 

Morgan N, Harries LW, Castaño L, Ellard S, Ferrer J, Perez 

de Nanclares G, Hattersley AT 



other CIBERDEM groups: L Castaño. With other CIBERs: 

CIBERER 



Collaborative European Effort to Develop Diabetes Diagnosis 

University of Exeter, CE_FP7_HealthB07: 2008-2012 

Principal Investigator: Jorge Ferrer 

Biology of Liver and Pancreatic Development and Disease 

University of Birmingham, CE_FP7_PEOPLE-ITN-08, Marie 

Curie Training Network: 2009-2013 



Regulación Epigenética y Plasticidad de las Células Beta 

Pancreáticas 


2009-2011 


Epibetacell- Empleo de epigenomas celulares para 

optimizar la terapia celular a partir de células madre 

Ministerio de Ciencia e Innovación, PLE2009-0162: 



Private funds 

Analysis of the plasticity of pancreatic duct cells 

Juvenile Diabetes Research Foundation, 26-2008-633: 








CIBERDEM groups: J Ferrer, L Castaño, E Blázquez, M 

Vallejo ■ 

Pancreatic bile duct. In red CK19; in green Hnf1b; in blue topro3. 

110 CibeRdem

Diabetes and obesity: 

biopathology and cellular plasticity 


www.diabetisiobesitat.org 

Principal Investigator Ramon Gomis rgomis@clinic.ub.es Associate researchers Roser Casamitjana, Ignacio Conget, Enric Esmatjes, 

Liliam Flores, Rosa Gasa, Felicia Hanzu, Marga Giménez, Belén Nadal, Marcelina Parrizas, Josep Vidal, Emilio Ortega, Sara Cervantes, 

M Carmen Carmona, Marc Claret, María José Coves Postdoctoral fellows Rebeca Fernández, Nathalie Nicod, Sandra Rebuffat 

PhD students Jordi Altirriba, Marta Amigó, Joana Duarte, Miriam Ejarque, Katerina Papageorgiou, Fabián Pardo, Gemma Pujadas 

Lab manager Marta Julià Lab technicians Yaiza Esteban, Ainhoa García, Sandra Piquer, Lídia Sánchez 












PhD theses: 3 

Keywords 

Clinical diabetes. Endothelium. Islet degeneration and 

damage. Islet development. Weight regulation and obesity. 


-The effects of pancreatic-mesenteric adipose tissue on 

beta cell plasticity. 

-Crosstalk between adipose tissue and endothelium in 

obesity and type 2 diabetes: the role of adipocytokines 

in the aetiology and development of the atherothrombotic 

complications in both diseases. 

-The molecular determinants involved in pancreatic 

beta-cell apoptosis and regeneration: clinical 

applications. 

-Transcriptional networks which control beta-cell population 

and function. 

-Metabolic and molecular targets of the antidiabetic effect 

of sodium tungstate. 

-The role of the hypothalamus in energy homeostasis control in 

obesity. 


111

-Epigenetic regulation of adipogenesis. 

-Genetic determinants involved in the risk of type 2 diabetes. 

Publications* 


BACE2 plays a role in the insulin receptor trafficking in 

pancreatic beta cells 

Casas S, Casini P, Piquer S, Altirriba J, Soty M, Cadavez L, 

Gomis R, Novials A 

Am J Physiol Endocrinol Metab, 299, E1087-E1095 (2010) 

IF: 4.395 first quartile. With other CIBERDEM groups: A Novials 

Histone demethylase LSD1 regulates adipogenesis 

Musri MM, Carmona MC, Hanzu FA, Kaliman P, Gomis R, 

Párrizas M 



Authors: Conget I, Giménez M 

Editorial: Viguera Editores SL (2010) 

La cirugía de la obesidad y la buena mesa 

Authors: Violeta Moizé, Josep Vidal 

Editorial: Nestlé Nutrition (2010) 

Optimización del control glucémico mediante monitorización 

continua de glucosa interactiva en pacientes adultos y en 

edad pediátrica. Manual para profesionales no iniciados y 

avanzados 

Authors: Ampudia-Blasco F Javier, Conget I, Giménez M, 

Torres M 

Editorial: Medtronic Eds (2010) 

Pancreas and kidney transplantation: long-term endocrine 

function 

Mora M, Ricart MJ, Casamitjana R, Astudillo E, López I, 

Jiménez A, Fernández-Cruz L, Esmatjes E 

Clin Transplant, 24, E236-E240 (2010) 


Proof-of-concept trial on the efficacy of sodium tungstate 

in human obesity 

Hanzu F, Gomis R, Coves MJ, Viaplana J, Palomo M, Andreu 

A, Szpunar J, Vidal J 

Diabetes Obes Metab, 12, 1013-1018 (2010) 


Protein intake, body composition, and protein status 

following bariatric surgery 

Andreu A, Moizé V, Rodríguez L, Flores L, Vidal J 



Regeneration of insulin production by autologous bone marrow 

blood autotransplantation in patients with type 1 diabetes 

Esmatjes E, Montaña X, Real MI, Blanco J, Conget I, 

Casamitjana R, Rovira M, Gomis R, Marin P 



The role of transmembrane protein 27 (TMEM27) in islet 

physiology and its potential use as a beta cell mass biomarker 

Altirriba J, Gasa R, Casas S, Ramírez-Bajo MJ, Ros S, 

Gutierrez-Dalmau A, Ruiz de Villa MC, Barbera A, Gomis R 


IF: 6.551 first decile. With other CIBERDEM groups: A Novials 

Books 

Guia de diabetes mellitus tipo 2. Actualización para el 

Especialista 

TMEM27 is mainly produced in beta cells in the human pancreas. 

Representative immunofluorescence images of human healthy (a– 

d) and diabetic (e–h) pancreases using antibodies against TMEM27 

(a, e), insulin (b, f) and glucagon (c, g). Merged images are shown in 

d and h. All images are at ×40 magnification. No staining was visible 

in exocrine tissue in either control or diabetic pancreases. Image 

from: Diabetologia, 2010. 



112 CibeRdem

Utilidad de la ecografía arterial en el diagnóstico precoz de 

la aterosclerosis en la diabetes 

Authors: Giménez M, Conget I 

Editorial: Biblioteca de la Sociedad Española de Diabetes (2010) 

Book chapters 

Book: Endocrinologia, 2nd Edition 

Chapter: Nefropatía diabética 

Author: E Esmatjes 

Pages: 673-677 

Editorial: Editorial Panamericana (2010) 

Book: Trasplante de Páncreas en España 

Chapter: Efecto del trasplante de páncreas sobre el control 

metabólico y las complicaciones de la diabetes 

Authors: Esmatjes E, Ricart MJ, Astudillo E, Fernández-Cruz L 

Pages: 157-167 

Editorial: Ed. Fundación Canaria Salud y Sanidad de 

Tenerife (2010) 



FOOD FOR LIFE - Supporting Healthy Lifestyles in the 

Mediterranean Area 

Marie Curie Actions, International Research Staff Exchange 

Scheme (FP7-PEOPLE-IRSES-2008), 230848: 2009-2011 

Principal Investigator: Ramon Gomis 

The role of adipose tissue in obesity: beta cell crosstalk 

(ADIBET) 

FP7 PEOPLE-2007-3-1-IAPP, 218131: 2008-2011 



Molecular targets induced by tungstate in obesity 


2006-2011 


Transcriptional cascade induced by neurogenin3 in the 

pancreas: a study of the transcription factors math6 and ebf1 

Ministerio de Ciencia e Innovación, BFU2008-02299/BMC: 

2009-2011 

Principal Investigator: Rosa Gasa 

The role of LSD1 histone demethylase in adipogenesis 



Principal Investigator: Marcelina Parrizas 

The role of miRNAs in hypothalamic populations of neurons 

in energy and glucose homeostasis: potential targets for 

obesity and diabetes treatment 


Principal Investigator: Marc Claret 

The effects of gastric bypass on blood pressure and 

endothelial dysfunction in severely obese subjects 

Ministerio de Sanidad y Consumo, FIS PI070124: 


Principal Investigator: Enric Esmatjes 


Estudio aleatorizado prospectivo sobre los efectos del 

tratamiento médico intensivo con o sin bypass gástrico en 

Y de Roux, sobre el grueso de la íntima media carotidea en 

enfermos con obesidad grave I 

Agència d’Avaluació de Tecnologia i Recerca Mèdiques, 

Generalitat de Catalunya: 2009-2011 

Principal Investigator: Josep Vidal 

Experimental diabetes, cellular and molecular research in 

experimental diabetic models 

Direcció General de Recerca, Generalitat de Catalunya, 

2009 SGR 1426: 2009-2013 


Private funds 

GLP-1 y resolución tras el bypass gástrico de la diabetes 

tipo 2 asociada a obesidad 

Mútua Madrileña: 2009-2011 

Principal Investigator: Josep Vidal 






CIBERDEM groups: R Gomis, X Correig, A Novials 





CIBERDEM groups: R Gomis, A Novials, ML Villanueva Peñacarrillo 




Project coordinator: Ramon Gomis 

CIBERDEM groups: R Gomis, X Correig, JJ Guinovart 


and their involvement in the ethiogenesis of diabetes mellitus 



CIBERDEM groups: R Gomis, JJ Guinovart, R Simó 





113



CIBERDEM groups: R Gomis, M Benito, D Burks 




CIBERDEM groups: R Gomis, F Soriguer, R Carmena, L 

Castaño, M Serrano Ríos, J Vendrell 



CIBERDEM Biobank Nodes: R Gomis, A Novials, J Vendrell, 

L Masana, L Castaño, M Serrano Ríos, F Soriguer, R 

Carmena, F Blanco Vaca 


Trial, randomized, double-blind, placebo controlled and 

peer-group to assess the efficacy and safety of Linagliptin 

(5 mg) orally administered once a day for more than 52 

weeks in type 2 diabetes patients combined with insulin as 

base treatment. Phase III 

Boehringer Ingelheim: 2009-in progress 

Researcher: Ramon Gomis 

Multicenter trial, international, randomized and 2x2 factorial 

to assess the effects of Lantus (glargin insulin) compared to 

the standard treatment with omega 3 fatty acids compared 

to placebo, in the decrease in cardiovascular morbility and 

mortality in high risk patients with altered fasting glucose 

(AFG), decrease in glucose tolerance (TGD) or type 2 

diabetes in initial stages. Phase IV 

Sanofi Aventis: 2004- in progress 

Steering Committee Member: Ramon Gomis 

Observational follow-up study of patients previously 

attended in exubera controlled clinical trials. Phase IV 

Pfizer: 2009- in progress 


AstraZeneca Farmacéutica: 2008-2010 


Glucose Control in Type 2 Diabetes Mellitus with insulin 

pump therapy. OpT2mise Project 

IP for the center and Steering Committee Member: Ignacio 

Conget 

Sensing With Insulin Pump Therapy to Control HbA1c. 

SWITCH study 

IP for the center and Steering Committee Member: Ignacio 

Conget 

Proyecto REWIND Reducing CV Events by a Weekly INcretin 

in Diabetes 

2010-in progress 

Coordinator and Steering Committee Member: Ignacio 

Conget 

PhD theses 

Efecte hipotalàmic del tungstat de sodi i la seva relació 

amb la via de la leptina: una posible teràpia antiobesitat 

Author: Marta Amigó Correig 

Thesis advisors: Ramon Gomis, M Carmen Carmona 



Bases moleculares del efecto del tungstato de sodio sobre 

la plasticidad pancreática y Tmem27 

Author: Jordi Altirriba Gutiérrez 

Thesis advisor: Ramon Gomis 


Thesis defense date: July 27, 2010 

Plasticitat de la cèl·lula beta en l’obesitat 

Author: Núria Palau Balañá 

Thesis advisor: Ramon Gomis 


Thesis defense date: July 29, 2010 ■ 

Study of 24 weeks, international, randomized, peer-group, 

double-blind and placebo controlled with an extended period 

of 24 weeks to assess efficacy and safety of dapaglifocin 

added to treatment of type 2 diabetes mellitus patients with 

poor control of glycaemia with insulin. Phase III 

Astra Zeneca : 2009- in progress 


Study of 24 weeks and 28 weeks of follow-up, multicenter, 

randomized, double-blind, age stratified, and placebo 

controlled to evaluate the efficacy and safety of 

dapagliflozin 10mg once a day, in DM2 patients with 

history of cardiovascular disease, hypertensive and with 

poor control of glycaemia with their usual treatment. 

Phase III 

114 CibeRdem

Islet cell and stem cell physiology 

Universidad Pablo de Olavide, Centro Andaluz de Biología Molecular y Medicina Regenerativa, Sevilla 

www.cabimer.es 

Principal Investigator Franz Martín fmarber@upo.es Associate researchers Francisco Bedoya, Genoveva Berná, Gladys Cahuana, 

Remedios Ramírez, Bernat Soria, Juan Tejedo Postdoctoral fellows Anabel Rojas, Ángeles de la Torre Ortega PhD student Manuel 

Carrasco Lab technicians Raquel Araujo, Irene Díaz Contreras, Antonio Cárdenas, Ana Belén Hitos, Sergio Mora 










Patents: 1 

-The role of NO in embryonic stem cell differentiation and 

survival. 

-Transcriptional network operating during pancreas 

development. 

-The differentiation of human embryonic stem cells (hESCs) 

to beta-cell like. 

-The obtention of IPS and differentiation to beta-cell like. 

-The role of endothelial factors in adult islet-cell proliferation. 

-The regulation of beta-cell survival. 

-Clinical trials for diabetes complications. 

Keywords 

Beta-cell signal transduction. Islet degeneration and 

damage. Islet development. Stem cells. Clinical trial. 


-The study of interactive pathways implicated in «stemness». 

Publications* 


Direct transcriptional regulation of Gata4 during early 

endoderm specification is controlled by FoxA2 binding to 

an intronic enhancer 

Rojas A, Schachterle W, Xu SM, Martín F, Black BL 




115

Dev Biol, 346, 346-355 (2010) 


Nitric oxide repression of Nanog promotes mouse 

embryonic stem cell differentiation 

Mora-Castilla S, Tejedo JR, Hmadcha A, Cahuana GM, 

Martín F, Soria B, Bedoya FJ 

Cell Death Differ, 17, 1025-1033 (2010) 


Pancreatic islet cells: a model for calcium-dependent 

peptide release 

Soria B, Tuduri E, Gonzalez A, Hmadcha A, Martin F, Nadal 

A, Quesada I 

HFSP Journal, 4, 52-60 (2010) 

IF: 1.600 first quartile. With other CIBERDEM groups: A Nadal 



TERCEL Network 

Instituto de Salud Carlos III, RD06/0010/0025: 2010-2011 

Principal Investigator: Bernat Soria 

Associate investigators: Franz Martín, Karim Hmdcha, 

Francisco Bedoya, Juan Tejedo 

Molecular characterization of protective action of NO on 

the pancreatic beta-cell 

Ministerio de Ciencia e Innovación, SAF-2007-602105: 


Principal Investigator: Francisco J Bedoya 

Associate investigators: Gladys M Cahuana, Juan R Tejedo 

The role of GATA4 transcription factor in endoderm and 

pancreas development 


Principal Investigator: Anabel Rojas 

Diabetes mellitus cell therapy: the role of intercellular 

signalling pathways and intracellular material transfer 

Instituto de Salud Carlos III, PI-10/00964: 2010-2013 


Associate investigators: Franz Martín, Karim Hmadcha, 

Miguel Martín, Lourdes Acosta, Ana Serna, Alfredo 

Santana, Rafael Ruiz, Antonio de la Cuesta, Inmaculada 

Pérez Camacho, Yolanda Aguilera, Mónica Navarro 

Cell therapy for critical lower-limb ischemia in type 

2 diabetes insulinized patients: a study of insulin 

demand 

MSPS/Dirección General de terapias Avanzadas, TRA-120: 



Associate investigators: Karim Hmadcha, Rafael Ruiz, 

Antonio de la Cuesta, Inmaculada Pérez Camacho, 

Franz Martín 


The role of endothelial factors in the obtention of insulinsecreting 

cells from adult pancreatic stem cells 

Consejería de Salud, Junta de Andalucía, PI00022/2008: 

2009-2012 

Principal Investigator: Franz Martín 

Associate investigators: Patricia Moreno, Elvira León, 

Verónica Rivero, Javier Navarro 

NO regulation of mouse and human beta-cell and 

pancreatic islet survival during the isolation process 


2008-2011 

Principal Investigator: Juan R Tejedo 

Associate investigators: Francisco J Bedoya, Gladys M Cahuana 

Transcriptional control during endoderm pancreas development 



Principal Investigator: Anabel Rojas 

Associate investigators: Raquel Araujo 

Monoclonal antibody characterization 

Fundación Progreso y Salud: 2010-2011 

Principal Investigator: Franz Martín 

Associate investigators: Genoveva Berná, Gladys M Cahuana 




beta cells 

ANTIBECELL: 2009-2010 

Coordinator: Juan Tejedo 

CIBERDEM groups: F Martín, E Montanya, A Nadal 


Intraarterial infusion of autologous mesenchymal stem cells 

from adipose tissue in diabetic patients with chronic critical 

limb ischemia. Phases I and II 

IATA (Iniciativa Andaluza de Terapias Avanzadas), 

(CeTMAd/ICPD2008), ClinicalTrials.gov NCT01079403: 


Name of the participants: Ruiz R, De la Cuesta A, Soria B, 

Hmadcha K 

Cellular therapy for type 2 diabetic patients with CLI: Study 

of Insulin needs. Phases I and II 

IATA (Iniciativa Andaluza de Terapias Avanzadas), 

(CeTMOTa/ICPDI/2010) CT 2010-019774-33: 2010-2011 


Hmadcha K 

Multicenter clinical trial for the evaluation of intraarterial 

infusion of autologous marrow derived mononuclear cells 

116 CibeRdem

in diabetic patients with chronic critical limb ischemia. 

Phases I and II 

IATA (Iniciativa Andaluza de Terapias Avanzadas), (CMMo/ 

ICPC/2008), ClinicalTrials.gov NCT00987363: 2009-2010 


Hmadcha K 

Autologous mesenchymal stem cells from adipose tissue 

in patients with secondary progressive multiple sclerosis. 

Phases I and II 

IATA (Iniciativa Andaluza de Terapias Avanzadas), (CMM/ 

EM/2008), ClinicalTrials.gov NCT01056471: 2010-2011 

Name of the participants: Fernández O, Izquierdo G, Soria 

B, Hmadcha K 

Patents 

National patent 

A method for the in vitro proliferation of cells coming from 

tissues of endodermic origin 

Patent application number: P201030365 

Inventors: Adrian Khoo, Franz Martín, Bernat Soria 

FPS-UPO (2010) ■ 

9.5 day-murine embryo showing Pdx1 expression using X-Gal 

dye. 

Culture of pancreatic progenitor cells expressing cytokeratin 19 

(green) and insulin (red). 


117

Group of Research into Diabetes and Metabolism 

Hospital Universitari de Bellvitge, Institut d’Investigació Biomèdica de Bellvitge, Universitat de Barcelona 

www.bellvitgehospital.cat 

www.idibell.cat 

www.ub.edu 

Principal Investigator Eduard Montanya montanya@ub.edu Associate researchers José Manuel Gómez, Montserrat Nacher, Manuel 

Pérez, Juan Soler, Noèlia Téllez, Nuria Vilarrasa Research assistant Elisabet Estil·les PhD students Jorge Caballero, Mar Pairó, Marina 

Vilaseca Lab technician Jessica Escoriza 


Publications: 6, 4 of them in the first decile and 2 in the 

first quartile 









PhD theses: 1 

Keywords 

Islet degeneration and damage. Islet transplantation. Stem 

cells. Gastro-entero pancreatic factors. Weight regulation 

and obesity. 


The study of the cellular and molecular biology of pancreatic islet 

cells and the study of insulin resistance in obesity. The specific 

focus of the group is the mechanisms of destruction, protection 

and regeneration of pancreatic beta cells with a particular 

interest in the cell therapy of diabetes, and the metabolic and 

molecular regulation of insulin resistance by adipose tissue. 

Publications* 



Gaulton KJ, Nammo T, Pasquali L, Simon JM, Giresi PG, 

Fogarty MP, Panhuis TM, Mieczkowski P, Secchi A, Bosco D, 




other CIBERDEM groups: J Ferrer 



118 CibeRdem

Liraglutide versus sitagliptin for patients with type 2 

diabetes who did not have adequate glycaemic control with 

metformin: a 26-week, randomised, parallel-group, openlabel 

trial 

Pratley RE, Nauck M, Bailey T, Montanya E, Cuddihy R, Filetti 

S, Thomsen AB, Søndergaard RE, Davies M; 1860-LIRA- 

DPP-4 Study Group 

Lancet, 375, 1447-1456 (2010) 


Paired subcutaneous and visceral adipose tissue 

aquaporin-7 expression in human obesity and type 2 

diabetes: differences and similarities between depots 

Miranda M, Escoté X, Ceperuelo-Mallafré V, Alcaide MJ, 

Simón I, Vilarrasa N, Wabitsch M, Vendrell J 



other CIBERDEM groups: J Vendrell 

Relation between human LPIN1, hypoxia and endoplasmic 

reticulum stress genes in subcutaneous and visceral 

adipose tissue 

Miranda M, Escoté X, Ceperuelo-Mallafré V, Megía A, 

Caubet E, Näf S, Gómez JM, González-Clemente JM, 

Vicente V, Vendrell J 



J Vendrell 

Switching to once-daily liraglutide from twice-daily 

exenatide further improves glycemic control in patients with 

type 2 diabetes using oral agents 

Buse JB, Sesti G, Schmidt WE, Montanya E, Chang CT, 

Xu Y, Blonde L, Rosenstock J; Liraglutide Effect Action in 

Diabetes-6 Study Group 



The atrial natriuretic peptide and guanylyl cyclase-A system 

modulates pancreatic beta-cell function 

Ropero AB, Soriano S, Tudurí E, Marroquí L, Téllez N, Gassner 

B, Juan-Picó P, Montanya E, Quesada I, Kuhn M, Nadal A 



other CIBERDEM groups: A Nadal 



IMMEEDIA 

IRSES-247472: 2010-2014 

Coordinator: R Cobella 

Principal Investigator: Eduard Montanya 


Diferenciación de células productoras de insulina a partir 

de células troncales del páncreas adulto. Aplicación en 

terapia celular de la diabetes 


Principal Investigator: Eduard Montanya 


Grup de Recerca en Diabetes i Metabolisme 

Agència de Gestió d’Ajuts Universitaris i de Recerca 

(AGAUR), 2009SGR201: 2009-2013 

Coordinator: Eduard Montanya 

A study on the effect of human albumin versus human 

serum on the culture and transplant of human islets 

Centre de Medicina Regenerativa de Barcelona (CMRB), 

Generalitat de Catalunya, PROMT_0901-3: 2009-2010 

Principal Investigators: Eduard Montanya, Anna Novials 

CIBERDEM groups: E Montanya, A Novials 







CIBERDEM groups: E Montanya, J Vendrell, A Zorzano, J 

Balsinde, AM Gómez Foix, S Fernández Veledo, R Simó, 


Insulin-positive cells budding from metaplastic ducts during pancreas regeneration following 90% pancreatectomy. DIC: Differential Interference 

Contrast. 


119






CIBERDEM groups: E Montanya, X Correig, HF Escobar 

Morreale, R Simó, J Vendrell 

The production of monoclonal antibodies which selectively react 

with cell surface molecules on human pancreatic beta cells 



CIBERDEM groups: HF Montanya, F Martín, A Nadal 


Efecto de Liraglutida en comparación con sitagliptina, 

ambas en combinación con metformina en sujetos con 

diabetes tipo 2. Ensayo de 26 semanas, aletaorizado, 

abierto, con comparador activo, de tres grupos paralelos, 

multicéntrico, multinacional. Phase III 

Novo Nordisk, A/S: 2008-2010 

Name of the participants: Eduard Montanya, Manuel Pérez, 

Jorge Caballero 

Estudio multicéntrico, randomizado, doble ciego, 

con doble enmascaramiento, controlado frente a un 

comparador activo para evaluar la eficacia, seguridad 

y tolerancia de Taspoglutida (RO5073031) comparado 

con Pioglitazona en pacientes con diabetes mellitus tipo 

2 controlados inadecuadamente con sulfonilurea (SU) 

en monoterapia o con la combinación metformina más 

sulfonilurea. Phase III 

Hoffmann La Roche: 2009-2011 

Name of the participants: Eduard Montanya, Manuel Pérez, 

Jorge Caballero 

PhD theses 

Expresion y distribución de la maquinaria proteica de la 

secreción de insulina. Regulación mediada por glucosa y 

fibronectina 

Author: Ruben Darío Fernández Montes 

Thesis advisors: Eduard Montanya, Montserrat Nacher 


Thesis defense date: June 4, 2010 ■ 

120 CibeRdem

Unit of Cell Physiology and Nutrition IB-UMH 

Instituto de Bioingeniería, Universidad Miguel Hernández, Elx 

http://diabetes.umh.es 

Principal Investigator Angel Nadal nadal@umh.es Associate researchers Esther Fuentes, Elena García, Ivan Quesada, Cristina Ripoll, 

Ana Belén Ropero Postdoctoral fellows Paloma Alonso Magdalena, Sergi Soriano, Elaine Vieira PhD students Ernesto Caballero, Marta 

García Arévalo, Alejandro González, Laura Marroquí Lab technicians Pablo Juan Picó, María Luisa Navarro, Ana Belén Rufete 











Keywords 

Beta-cell signal transduction. Hormone receptors. 

Hormones (non-insulin), action. Insulin secretion. Insulin 

sensitivity and resistance. Cytokines. 


-The role of oestrogen receptors in the physiology of the 

islet of Langerhans. We study the actions of oestrogens 

and environmental oestrogenic pollutants in the function of 

pancreatic alpha and beta cells with an emphasis on the 

molecular mechanisms involved. 

-Signal transduction pathways involved in the function 

of alpha, beta and delta cells. We study the activation 

of signalling pathways by leptin receptors and its 

consequences in alpha- and beta-cell function. 

-The role of ANP (atrial natriuretic peptide) 

receptors in beta-cell function and blood glucose 

homeostasis. 

Publications* 


Bisphenol A exposure during pregnancy disrupts glucose 

homeostasis in mothers and adult male offspring 

Alonso-Magdalena P, Vieira E, Soriano S, Menes L, Burks D, 

Quesada I, Nadal A 




121


IF: 6.191 first decile. With other CIBERDEM groups: D Burks 

Glucocorticoids in vivo induce both insulin hypersecretion 

and enhanced glucose sensitivity of stimulus-secretion 

coupling in isolated rat islets 

Rafacho A, Marroquí L, Taboga SR, Abrantes JL, Silveira 

LR, Boschero AC, Carneiro EM, Bosqueiro JR, Nadal A, 

Quesada I 



Minimal state models for ionic channels involved in glucagon 

secretion 

Gonzalez-Velez V, Gil A, Quesada I 

Math Biosci Eng, 7, 793-807 (2010) 


Pancreatic islet cells: a model for calcium-dependent 

peptide release 

Soria B, Tuduri E, Gonzalez A, Hmadcha A, Martin F, Nadal 

A, Quesada I 


IF: 1.600 first quartile. With other CIBERDEM groups: F Martín 

Reduced insulin secretion in protein malnourished mice is 

associated with multiple changes in the beta-cell stimulussecretion 

coupling 

Soriano S, Gonzalez A, Marroquí L, Tudurí E, Vieira E, 

Amaral AG, Batista TM, Rafacho A, Boschero AC, Nadal A, 

Carneiro EM, Quesada I 



The atrial natriuretic peptide and guanylyl cyclase-A system 

modulates pancreatic beta-cell function 

Ropero AB, Soriano S, Tudurí E, Marroquí L, Téllez N, 

Gassner B, Juan-Picó P, Montanya E, Quesada I, Kuhn M, 

Nadal A 




Editorial 

Position paper: Rapid responses to steroids: current status 

and future prospects 

Wendler A, Baldi E, Harvey BJ, Nadal A, Norman A, Wehling M 





Circadian regulation in the control of insulin and glucagon 

release and its role in Type 2 diabetes 

European Commission (Programme PEOPLE), 234879: 

2009-2011 

Principal Investigator: Ivan Quesada 

Associate investigator: Elaine Vieira 

A 

B 

Inmunocytochemistry for Bromodeoxyuridine (5-bromo-2’-deoxyuridine). A) A non-endocrine cell from the pancreas during mitosis probably 

at later anaphase B) A beta cell after mitosis and during cytokinesis. 

122 CibeRdem


Efectos a corto y largo plazo de la activación de los 

receptores de estrógenos sobre el contenido, la secreción 

y la supervivencia de la célula-beta pancreática 

DGICYT, MICINN: 2009-2011 

Principal Investigator: Angel Nadal 

Efecto de la leptina sobre la expresión y secreción de 

glucagón y sobre la plasticidad del páncreas endocrino 

DGICYT, MICINN, BFU2007-67607/BFI: 2007-2010 

Principal Investigator: Ivan Quesada 

Associate investigators: Cristina Ripoll, Elena García, Laura 

Marroquí, Sergi Soriano, Alejandro González 


Papel de los péptidos natriuréticos en el síndrome 

metabólico. Estudio sobre la homeostasis de la glucosa 

UMH-Bancaja: 2009-2010 

Principal Investigator: Ana B Ropero 

Ayuda complementaria al proyecto: Efectos a corto y largo 

plazo de la activación de los receptores de estrógenos 

sobre el contenido, la secreción y la supervivencia de la 

célula- beta pancreática 

Generalitat Valenciana: 2010 

Principal Investigator: Angel Nadal 




beta cells 



CIBERDEM groups: A Nadal, F Martín, E Montanya ■ 


123

Metabolic and molecular disturbances in diabetes 


www.diabetisiobesitat.org 

Principal Investigator Anna Novials anovials@clinic.ub.es Associate researcher Joan Marc Servitja Postdoctoral fellows Maud Soty, 

Paola Casini Research assistants Serafín Murillo, Laura Brugnara PhD students Montse Visa, Lisa Cadavez, Alba Moreno Lab technician 

Carlos Castaño 


Publications: 2, 1 in the first decile and 1 in the first quartile 








Keywords 

Islet amyloid polypeptide/amylin. Islet degeneration and 

damage. Transcription factors. Exercise. Endothelium. 


-Mechanisms of pancreatic islet dysfunction in type 2 

diabetes mellitus, in particular, the process of cytotoxicity 

as induced by amyloidogenesis. 

-Signalling and transcriptional networks in the pancreatic 

beta cell, mainly related to the modulation of the 

transcriptional programme under stress conditions. 

-Impact of lifestyle on diabetes: metabolic and molecular 

responses to exercise and nutrition in diabetic patients. 

Publications* 


BACE2 plays a role in the insulin receptor trafficking in 

pancreatic beta cells 

Casas S, Casini P, Piquer S, Altirriba J, Soty M, Cadavez L, 

Gomis R, Novials A 


IF: 4.395 first quartile. With other CIBERDEM groups: R Gomis 

The role of transmembrane protein 27 (TMEM27) in islet 

physiology and its potential use as a beta cell mass biomarker 



124 CibeRdem

Altirriba J, Gasa R, Casas S, Ramírez-Bajo MJ, Ros S, 

Gutierrez-Dalmau A, Ruiz de Villa MC, Barbera A, Gomis R 


IF: 6.551 first decile. With other CIBERDEM groups: R Gomis 



Epigenetic control of gene expression in pancreatic islets 

European Foundation for the Study of Diabetes (EFSD)-Lilly 

Research Fellowship: 2010 

Principal Investigator: Joan Marc Servitja 


The role of the BACE enzyme (beta-site amyloid precursor 

protein cleaving enzyme) in pancreatic islet function 

Ministerio de Sanidad y Consumo, PI080088: 2009-2011 

Principal Investigator: Anna Novials 

Associate investigators: Sílvia Casas, Paola Casini, Maud Soty 

Design, characterization and follow-up of training designed to 

produce metabolic improvements in type 2 diabetic patients 

Ministerio de Ciencia e Innovación, DPS2008-06922: 

2009-2011 

Principal Investigator: Joan Aureli Cadefau 

Associate investigator: Anna Novials 

A study of the pancreatic islet response to hypoxia: role of HIF-1 

Ministerio de Educación y Ciencia, BFU2006-09072/BFI. 

PI015429: 2006-2010 

Principal Investigator: Joan Marc Servitja 


A study of the effect of human albumin versus human 

serum on the culture and transplant of human islets 

Centre de Medicina Regenerativa de Barcelona (CMRB), 

Generalitat de Catalunya, PROMT_0901-3: 2009-2010 

Principal Investigators: Anna Novials, Eduard Montanya 

CIBERDEM groups: A Novials, E Montanya 






CIBERDEM groups: A Novials, X Correig, R Gomis 





CIBERDEM groups: A Novials, R Gomis, ML Villanueva Peñacarrillo 



Exercise test at the Diabetes and Exercise Unit. 


125

CIBERDEM Biobank Nodes: A Novials, R Gomis, J Vendrell, 

L Masana, L Castaño, M Serrano Ríos, F Soriguer, R Carmena, 

F Blanco Vaca 


Multicenter trial, international, randomized and 2x2 factorial 

to assess the effects of Lantus (glargin insulin) compared to 

the standard treatment with omega 3 fatty acids compared 

to placebo, in the decrease in cardiovascular morbility and 

mortality in high risk patients with altered fasting glucose 

(AFG), decrease in glucose tolerance (TGD) or type 2 

diabetes in initial steps. Phase III 

Sanofi-Aventis: 2004-in progress 

Researcher: Anna Novials ■ 

126 CibeRdem

Transcriptional mechanisms of pancreatic function 

Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, 

Universidad Autónoma de Madrid 

www.iib.uam.es 

Principal Investigator Mario Vallejo mvallejo@iib.uam.es Postdoctoral fellows María Natacha Díaz, Mercedes Mirasierra PhD students 

Patricia García, Laura Ruiz Lab manager Antonio Fernández 


Publications: 2, 1 in the first quartile and 1 in the second quartile 




Keywords 

Insulin synthesis. Islet degeneration and damage. Islet 

development. Transcription factors. 


-The characterization of phenotypic alterations of 

pancreatic islets in the absence of Alx3. 

-The requirement of Alx3 for the maintenance of glucose 

homeostasis in vivo. 

-The identification of transcriptional targets regulated by Alx3. 

-The determination of the expression pattern of Alx3 during 

pancreas development. 

-The role of Alx3 in the regulation of the development of the neural 

tube and vulnerability to hyperglycaemic insult in its absence. 

Publications* 


Alx3-deficient mice exhibit folic acid-resistant craniofacial 

midline and neural tube closure defects 

Lakhwani S, García-Sanz P, Vallejo M 



Activity-dependent somatostatin gene expression is 

regulated by cAMP-dependent protein kinase and Ca2+calmodulin 

kinase pathways 

Sánchez-Muñoz I, Sánchez-Franco F, Vallejo M, Fernández 

A, Palacios N, Fernández M, Cacicedo L 

J Neurosci Res, 88, 825-836 (2010) 





127



A pleiotropic role for the homeoprotein Alx3 in the 

maintenance of cell viability and survival 

MICINN, BFU2008-01283: 2009-2011 

Principal Investigator: Mario Vallejo 






CIBERDEM groups: M Vallejo, L Castaño, J Ferrer, E Blázquez 






CIBERDEM groups: M Vallejo, C Álvarez, E Blázquez, 

D Burks, M Serrano Ríos ■ 

Immunofluorescence images taken by confocal microscopy showing 

pancreatic islets of wild type or Alx3-deficient mice stained for 

somatostatin (green) or glucagon (red). Note the altered distribution 

of cells, which are not confined to the periphery in the Alx3- 

deficient islet. 

128 CibeRdem

Epilogue

Principal Investigator index 

Álvarez, Carmen .................................................................................92 

Balsinde, Jesús ..................................................................................54 

Benito, Manuel ...................................................................................34 

Blanco Vaca, Francisco ............................................................................56 

Blázquez, Enrique ................................................................................94 

Bosch, Fàtima ...................................................................................97 

Burks, Deborah .................................................................................101 

Carmena, Rafael .................................................................................59 

Castaño, Luis ...................................................................................103 

Correig, Xavier. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .36 

de Pablo, Flora .................................................................................107 

Escobar Morreale, Héctor F ........................................................................62 

Fernández Veledo, Sonia ...........................................................................38 

Ferrer, Jorge ...................................................................................109 

Gómez Foix, Anna Maria ...........................................................................40 

Gomis, Ramon ..................................................................................111 

Guinovart, Joan J ................................................................................42 

Ibáñez, Lourdes .................................................................................65 

Martín, Franz ...................................................................................115 

Martínez Valverde, Ángela .........................................................................44 

Masana, Lluís ...................................................................................69 

Montanya, Eduard ...............................................................................118 

Nadal, Angel ...................................................................................121 

Novials, Anna ...................................................................................124 

Serrano Ríos, Manuel .............................................................................73 

Simó, Rafael ....................................................................................76 

Soriguer, Federico ................................................................................81 

Vallejo, Mario ...................................................................................127 

Vázquez Carrera, Manuel ..........................................................................85 

Vendrell, Joan J ..................................................................................87 

Villanueva Peñacarrillo, María Luisa ..................................................................46 

Zorzano, Antonio .................................................................................48 


131

Keyword index* 

Beta-cell signal transduction. . . 34, 92, 97, 101, 115, 121 

Bioinformatics . . . . . . . . . . . . . . . . . . . . . . 36 

Biomarkers and Imaging. . . . . . . . . . . . . 36, 62, 69 

Carbohydrate metabolism . . . . . . . . . . . . 40, 42, 48 

Cardiac complications . . . . . . . . . . . . . . . . . . 85 

Catecholamines . . . . . . . . . . . . . . . . . . . . 107 

Clinical diabetes . . . . . . . . . . . . . . . .76, 103, 111 

Clinical trial. . . . . . . . . . . . . . . . . . . . . . . 115 

Cytokines. . . . . . . . . . . . . . . . 38, 44, 54, 65, 121 

Endothelium . . . . . . . . . . . . . . . . . .69, 111, 124 

Epidemiology. . . . . . . . . . . . . . . . . . . . . 73, 81 

Exercise . . . . . . . . . . . . . . . . . . . . 38, 48, 124 

Gastro-entero pancreatic factors . . . . . . . . . 92, 118 

Gene therapy. . . . . . . . . . . . . . . . . . . . . . . 97 

Genetics type 1 diabetes . . . . . . . . . . . . . . . 103 

Genetics type 2 diabetes . . . . . . . 56, 69, 73, 94, 109 

Genomics . . . . . . . . . . . . . . . . . . . 48, 73, 109 

Glucose transport . . . . . . . . . . . . . . . . . . 38, 46 

Hormone receptors . . . . . . . . . .44, 46, 94, 107, 121 

Hormones (non-insulin), action . . . . . . . . . . . . 121 

Incretins . . . . . . . . . . . . . . . . . . . . . . . 46, 94 

Insulin action . . . . . . . . . . . . . . . . . . . 44, 48, 92 

Insulin secretion . . . . . . . . . . . . . . . . . . . . 121 

Insulin sensitivity and resistance 34, 38, 40, 42, 44, 46, 48, 

59, 62, 65, 69, 85, 87, 92, 97, 101, 107, 121 

Insulin synthesis . . . . . . . . . . . . . . . . . . . . 127 

Insulin therapy . . . . . . . . . . . . . . . . . . . . . . 81 

Islet amyloid polypeptide/amylin. . . . . . . . . . . . 124 

Islet degeneration and damage . . 92, 101, 111, 115, 118, 

124, 127 

Islet development . . . . . . . . .107, 109, 111, 115, 127 

Islet transplantation . . . . . . . . . . . . . . . . . . 118 

Lipid metabolism. . . . . 38, 40, 46, 48, 54, 56, 59, 76, 85 

Lipid signalling . . . . . . . . . . . . . . . . . . . . . . 54 

Lipids, lipoproteins . . . . . . . . . . . . . . . . 36, 56, 85 

Macrovascular disease . . . . . . . . . . . . . 34, 59, 69 

Metabolic surgery . . . . . . . . . . . . . . . . . . . . 62 

Metabolic syndrome . 42, 54, 56, 59, 65, 69, 73, 76, 81, 87 

Metabolomics . . . . . . . . . . . . . . . . . . . . . . 36 

Monogenic diabetes . . . . . . . . . . . . . . . . . . 103 

Neuropathy-somatic . . . . . . . . . . . . . . . . . . . 97 

Nutrigenomics . . . . . . . . . . . . . . . . . . . . . . 69 

Obesity . . . . . . . . . . . . . . . . . . . . . . . . . 101 

Oral pharmacological agents . . . . . . . 42, 48, 65, 103 

Paediatrics . . . . . . . . . . . . . . . . . . . . . . . . 65 

Pathogenic mechanisms . . . . . . . . . . . . . . . 34, 56 

Phospholipases . . . . . . . . . . . . . . . . . . . . . 54 

Polycystic ovary syndrome. . . . . . . . . . . . . . . . 62 

PPAR . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 

Prediction/prevention type 1 diabetes . . . . . . . . . 103 

Prediction/prevention type 2 diabetes . . . . . . . . 81, 87 

Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . 87 

Prevention of type 1 diabetes . . . . . . . . . . . . . . 73 

Prevention of type 2 diabetes . . . . . . . . . . . . 65, 69 

Proinsulin. . . . . . . . . . . . . . . . . . . . . . . . 107 

Protein metabolism. . . . . . . . . . . . . . . . . . . . 48 

Proteomics . . . . . . . . . . . . . . . . . . . . . . 62, 73 

Retinopathy. . . . . . . . . . . . . . . 42, 44, 76, 97, 101 

Stem cells . . . . . . . . . . . . . . 48, 94, 101, 115, 118 

Transcription factors . . . . . . . . . 48, 85, 109, 124, 127 

Weight regulation and obesity . .34, 44, 59, 76, 81, 87, 94, 

111, 118 

*Source: DIAMAP, Road Map for Diabetes Research in Europe. 

132 CibeRdem

Publications index* 


Gaulton KJ, Nammo T, Pasquali L, Simon JM, Giresi PG, Fogarty MP, Panhuis TM, Mieczkowski P, Secchi A, Bosco D, 



A single nucleotide polymorphism in STK11 influences insulin sensitivity and metformin efficacy in hyperinsulinemic girls 

with androgen excess 

López-Bermejo A, Díaz M, Morán E, de Zegher F, Ibáñez L 


Activation of peroxisome proliferator-activated receptor-{delta} by GW501516 prevents fatty acid-induced nuclear factor- 

{kappa}B activation and insulin resistance in skeletal muscle cells 

Coll T, Alvarez-Guardia D, Barroso E, Gómez-Foix AM, Palomer X, Laguna JC, Vázquez-Carrera M 


Activity-dependent somatostatin gene expression is regulated by cAMP-dependent protein kinase and Ca2+-calmodulin 

kinase pathways 

Sánchez-Muñoz I, Sánchez-Franco F, Vallejo M, Fernández A, Palacios N, Fernández M, Cacicedo L 

J Neurosci Res, 88, 825-836 (2010) 

Adenosine 5’-monophosphate-activated protein kinase-mammalian target of rapamycin cross talk regulates brown 

adipocyte differentiation 

Vila-Bedmar R, Lorenzo M, Fernández-Veledo S 


Alterations in the mitochondrial regulatory pathways constituted by the nuclear co-factors PGC-1alpha or PGC-1beta and 

mitofusin 2 in skeletal muscle in type 2 diabetes 

Zorzano A, Hernández-Alvarez MI, Palacín M, Mingrone G 

Biochim Biophys Acta, 1797, 1028-1033 (2010) Review 

Alx3-deficient mice exhibit folic acid-resistant craniofacial midline and neural tube closure defects 

Lakhwani S, García-Sanz P, Vallejo M 


APOH is increased in the plasma and liver of type 2 diabetic patients with metabolic syndrome 

Castro A, Lázaro I, Selva DM, Céspedes E, Girona J, Plana N, Guardiola M, Cabré A, Simó R, Masana L 





133

Association of selected ABC gene family single nucleotide polymorphisms with postprandial lipoproteins: results from the 

population-based Hortega study 

Abellán R, Mansego ML, Martínez-Hervás S, Martín-Escudero JC, Carmena R, Real JT, Redon J, Castrodeza-Sanz JJ, 

Chaves FJ 


Asymptomatic sleep-disordered breathing in premenopausal women awaiting bariatric surgery 

Lecube A, Sampol G, Lloberes P, Romero O, Mesa J, Morell F, Simó R 


BACE2 plays a role in the insulin receptor trafficking in pancreatic beta cells 

Casas S, Casini P, Piquer S, Altirriba J, Soty M, Cadavez L, Gomis R, Novials A 


Beneficial effects of PTP1B deficiency on brown adipocyte differentiation and protection against apoptosis induced by 

pro- and anti-inflammatory stimuli 

Miranda S, González-Rodríguez A, Revuelta-Cervantes J, Rondinone CM, Valverde AM 

Cell Signal, 22, 645-659 (2010) 

Bisphenol A exposure during pregnancy disrupts glucose homeostasis in mothers and adult male offspring 

Alonso-Magdalena P, Vieira E, Soriano S, Menes L, Burks D, Quesada I, Nadal A 


Carboxylation of osteocalcin affects its association with metabolic parameters in healthy children 

Prats-Puig A, Mas-Parareda M, Riera-Pérez E, González-Forcadell D, Mier C, Mallol-Guisset M, Díaz M, Bassols J, 

de Zegher F, Ibáñez L, López-Bermejo A 


Chronically increased glucose uptake by adipose tissue leads to lactate production and improved insulin sensitivity rather 

than obesity in the mouse 

Muñoz S, Franckhauser S, Elias I, Ferré T, Hidalgo A, Monteys AM, Molas M, Cerdán S, Pujol A, Ruberte J, Bosch F 


Circulating bactericidal/permeability-increasing protein (BPI) is associated with serum lipids and endothelial 

function 

Esteve E, Castro A, Moreno JM, Vendrell J, Ricart W, Fernández-Real JM 

Thromb Haemost, 103, 780-787 (2010) 

Circulating mononuclear cells nuclear factor-kappa B activity, plasma xanthine oxidase, and low grade inflammatory 

markers in adult patients with familial hypercholesterolaemia 

Real JT, Martínez-Hervás S, García-García AB, Civera M, Pallardó FV, Ascaso JF, Viña JR, Chaves FJ, Carmena R 

Eur J Clin Invest, 40, 89-94 (2010) 

Comparative gene expression profiling between human cultured myotubes and skeletal muscle tissue 

Raymond F, Métairon S, Kussmann M, Colomer J, Nascimento A, Mormeneo E, García-Martínez C, Gómez-Foix AM 

BMC Genomics, 11, 125 (2010) 

Cyclin G2 regulates adipogenesis through PPAR gamma coactivation 

Aguilar V, Annicotte JS, Escote X, Vendrell J, Langin D, Fajas L 


Cyclooxygenase 2 inhibition exacerbates palmitate-induced inflammation and insulin resistance in skeletal muscle 

cells 

Coll T, Palomer X, Blanco-Vaca F, Escolà-Gil JC, Sánchez RM, Laguna JC, Vázquez-Carrera M 


134 CibeRdem

dDOR is an EcR coactivator that forms a feed-forward loop connecting insulin and ecdysone signalling 

Francis VA, Zorzano A, Teleman AA 

Curr Biol, 20, 1799-1808 (2010) 

Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age 

Agudo J, Martin M, Roca C, Molas M, Bura AS, Zimmer A, Bosch F, Maldonado R 


Derepression of Polycomb targets during pancreatic organogenesis allows insulin-producing beta-cells to adopt a neural gene 

activity program 

van Arensbergen J, García-Hurtado J, Moran I, Maestro MA, Xu X, Van de Casteele M, Skoudy AL, Palassini M, Heimberg 

H, Ferrer J 

Genome Res, 20, 722-732 (2010) 

Diabetic neuropathy: electrophysiological and morphological study of peripheral nerve degeneration and regeneration in 

transgenic mice that express IFNbeta in beta cells 

Serafín A, Molín J, Márquez M, Blasco E, Vidal E, Foradada L, Añor S, Rabanal RM, Fondevila D, Bosch F, Pumarola M 

Muscle Nerve, 41, 630-641 (2010) 

Direct transcriptional regulation of Gata4 during early endoderm specification is controlled by FoxA2 binding to an intronic 

enhancer 

Rojas A, Schachterle W, Xu SM, Martín F, Black BL 


Disodium ascorbyl phytostanol phosphate (FM-VP4), a modified phytostanol, is a highly active hypocholesterolaemic 

agent that affects the enterohepatic circulation of both cholesterol and bile acids in mice 

Méndez-González J, Süren-Castillo S, Calpe-Berdiel L, Rotllan N, Vázquez-Carrera M, Escolà-Gil JC, Blanco-Vaca F 


Effect of intensive insulin therapy on macular biometrics, plasma VEGF and its soluble receptor in newly diagnosed 

diabetic patients 

Hernández C, Zapata MA, Losada E, Villarroel M, García-Ramírez M, García-Arumí J, Simó R 


Effect of nateglinide on the incidence of diabetes and cardiovascular events 

NAVIGATOR Study Group, Holman RR, Haffner SM, McMurray JJ, Bethel MA, Holzhauer B, Hua TA, Belenkov Y, Boolell 

M, Buse JB, Buckley BM, Chacra AR, Chiang FT, Charbonnel B, Chow CC, Davies MJ, Deedwania P, Diem P, Einhorn D, 

Fonseca V, Fulcher GR, Gaciong Z, Gaztambide S, Giles T, Horton E, Ilkova H, Jenssen T, Kahn SE, Krum H, Laakso M, 

Leiter LA, Levitt NS, Mareev V, Martinez F, Masson C, Mazzone T, Meaney E, Nesto R, Pan C, Prager R, Raptis SA, Rutten 

GE, Sandstroem H, Schaper F, Scheen A, Schmitz O, Sinay I, Soska V, Stender S, Tamás G, Tognoni G, Tuomilehto J, Villamil 

AS, Vozár J, Califf RM 


Effect of nut consumption on oxidative stress and the endothelial function in metabolic syndrome 

López-Uriarte P, Nogués R, Saez G, Bulló M, Romeu M, Masana L, Tormos C, Casas-Agustench P, Salas-Salvadó J 

Clin Nutr, 29, 373-380 (2010) 

Effect of the long-term regular intake of virgin olive oil on the phenolic metabolites in human fasting plasma 

Valls RM, Soler A, Girona J, Heras M, Romero MP, Covas MI, Solà R, Masana L, Motilva MJ 

J Pharm Biomed Anal, 53, 68-74 (2010) 

Effect of valsartan on the incidence of diabetes and cardiovascular events 

NAVIGATOR Study Group, McMurray JJ, Holman RR, Haffner SM, Bethel MA, Holzhauer B, Hua TA, Belenkov Y, Boolell 

M, Buse JB, Buckley BM, Chacra AR, Chiang FT, Charbonnel B, Chow CC, Davies MJ, Deedwania P, Diem P, Einhorn D, 

Fonseca V, Fulcher GR, Gaciong Z, Gaztambide S, Giles T, Horton E, Ilkova H, Jenssen T, Kahn SE, Krum H, Laakso M, 


135

Leiter LA, Levitt NS, Mareev V, Martinez F, Masson C, Mazzone T, Meaney E, Nesto R, Pan C, Prager R, Raptis SA, Rutten 

GE, Sandstroem H, Schaper F, Scheen A, Schmitz O, Sinay I, Soska V, Stender S, Tamás G, Tognoni G, Tuomilehto J, Villamil 

AS, Vozár J, Califf RM 


Emerging role of neuregulin as a modulator of muscle metabolism 

Gumà A, Martínez-Redondo V, López-Soldado I, Cantó C, Zorzano A 

Am J Physiol Endocrinol Metab, 298, E742-750 (2010) Review 

Epistasis of transcriptomes reveals synergism between transcriptional activators Hnf1alpha and Hnf4alpha 

Boj SF, Petrov D, Ferrer J 

PLoS Genet, 6, e1000970 (2010) 

Expression of glycogen phosphorylase isoforms in cultured muscle from patients with McArdle’s disease carrying the 

p.R771PfsX33 PYGM mutation 

Nogales-Gadea G, Mormeneo E, García-Consuegra I, Rubio JC, Orozco A, Arenas J, Martín MA, Lucia A, Gómez-Foix 

AM, Martí R, Andreu AL 


FABP4 plasma levels are increased in familial combined hyperlipidemia 

Cabré A, Lázaro I, Cofán M, Jarauta E, Plana N, Garcia-Otín AL, Ascaso JF, Ferré R, Civeira F, Ros E, Masana L 


Fatty acid-binding protein 4 is associated with endothelial dysfunction in patients with type 2 diabetes 

Aragonès G, Ferré R, Lázaro I, Cabré A, Plana N, Merino J, Heras M, Girona J, Masana L 


G protein-coupled receptor kinase 2 plays a relevant role in insulin resistance and obesity 

Garcia-Guerra L, Nieto-Vazquez I, Vila-Bedmar R, Jurado-Pueyo M, Zalba G, Díez J, Murga C, Fernández-Veledo S, Mayor 

F Jr, Lorenzo M 


Glucocorticoids in vivo induce both insulin hypersecretion and enhanced glucose sensitivity of stimulus-secretion coupling 

in isolated rat islets 

Rafacho A, Marroquí L, Taboga SR, Abrantes JL, Silveira LR, Boschero AC, Carneiro EM, Bosqueiro JR, Nadal A, Quesada I 


Hepatic overexpression of a constitutively active form of liver glycogen synthase improves glucose homeostasis 

Ros S, Zafra D, Valles-Ortega J, García-Rocha M, Forrow S, Domínguez J, Calbó J, Guinovart JJ 


Heterozygous glucokinase mutations and birth weight in Spanish children 

de Las Heras J, Martínez R, Rica I, de Nanclares GP, Vela A, Castaño L; Spanish MODY Group 


High AAV vector purity results in serotype- and tissue-independent enhancement of transduction efficiency 

Ayuso E, Mingozzi F, Montane J, Leon X, Anguela XM, Haurigot V, Edmonson SA, Africa L, Zhou S, High KA, Bosch F, Wright JF 

Gene Ther, 17, 503-510 (2010) 

Histone demethylase LSD1 regulates adipogenesis 

Musri MM, Carmona MC, Hanzu FA, Kaliman P, Gomis R, Párrizas M 


How ineffective hypertension control in subjects treated with angiotensin-converting enzyme inhibitors is related to 

polymorphisms in the renin-angiotensin-aldosterone system 

136 CibeRdem

Morales-Suárez-Varela MM, Mansego ML, Martín-Escudero JC, Llopis-González A, Chaves FJ, López-Izquierdo R, Frutos- 

Llanes R, Vicedo-Cabrera AM 

Eur J Pharm Sci, 39, 380-386 (2010) 

Human apolipoprotein A-II determines plasma triglycerides by regulating lipoprotein lipase activity and high-density 

lipoprotein proteome 

Julve J, Escolà-Gil JC, Rotllan N, Fiévet C, Vallez E, de la Torre C, Ribas V, Sloan JH, Blanco-Vaca F 

Arterioscler Thromb Vasc Biol, 30, 232-238 (2010) 

Hypothalamic-specific manipulation of Fto, the ortholog of the human obesity gene FTO, affects food intake in rats 

Tung YC, Ayuso E, Shan X, Bosch F, O’Rahilly S, Coll AP, Yeo GS 


Hypoxia promotes efficient differentiation of human embryonic stem cells to functional endothelium 

Prado-Lopez S, Conesa A, Armiñán A, Martínez-Losa M, Escobedo-Lucea C, Gandia C, Tarazona S, Melguizo D, Blesa D, 

Montaner D, Sanz-González S, Sepúlveda P, Götz S, O’Connor JE, Moreno R, Dopazo J, Burks DJ, Stojkovic M 

Stem Cells, 28, 407-418 (2010) 

Inhibition of PTP1B restores IRS1-mediated hepatic insulin signaling in IRS2-deficient mice 

González-Rodríguez A, Mas Gutierrez JA, Sanz-González S, Ros M, Burks DJ, Valverde AM 


Insulin resistance is related to impaired lung function in morbidly obese women: a case-control study 

Lecube A, Sampol G, Muñoz X, Lloberes P, Hernández C, Simó R 


Intake and home use of olive oil or mixed oils in relation to healthy lifestyles in a Mediterranean population. Findings from 

the prospective Pizarra study 

Soriguer F, Almaraz MC, García-Almeida JM, Cardona I, Linares F, Morcillo S, García-Escobar E, Dobarganes MC, Olveira 

G, Hernando V, Valdes S, Ruiz-de-Adana MS, Esteva I, Rojo-Martínez G 


Iron in obesity. An ancient micronutrient for a modern disease 

Zafon C, Lecube A, Simó R 

Obes Rev, 11, 322-328 (2010) Review 

Jejunal wall triglyceride concentration of morbidly obese persons is lower in those with type 2 diabetes mellitus 

Soriguer F, García-Serrano S, Garrido-Sánchez L, Gutierrez-Repiso C, Rojo-Martínez G, Garcia-Escobar E, García-Arnés 

J, Gallego-Perales JL, Delgado V, García-Fuentes E 


Lipidomic approaches to the study of phospholipase A2-regulated phospholipid fatty acid incorporation and remodelling 

Balgoma D, Montero O, Balboa MA, Balsinde J 

Biochimie, 92, 645-650 (2010) Review 

Lipopolysaccharide-binding protein and soluble CD14 in the vitreous fluid of patients with proliferative diabetic 

retinopathy 

Hernández C, Ortega F, García-Ramírez M, Villarroel M, Casado J, García-Pascual L, Fernández-Real JM, Simó R 

Retina, 30, 345-352 (2010) 

Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: 

a 26-week, randomised, parallel-group, open-label trial 

Pratley RE, Nauck M, Bailey T, Montanya E, Cuddihy R, Filetti S, Thomsen AB, Søndergaard RE, Davies M; 1860-LIRA- 

DPP-4 Study Group 

Lancet, 375, 1447-1456 (2010) 


137

Low body adiposity and high leptinemia in breast-fed infants born small-for-gestational-age 

Ibáñez L, Sebastiani G, Diaz M, Gómez-Roig MD, Lopez-Bermejo A, de Zegher F 

J Pediatr, 156, 145-147 (2010) 

Lpin1 in human visceral and subcutaneous adipose tissue: similar levels but different associations with lipogenic and 

lipolytic genes 

Miranda M, Escoté X, Alcaide MJ, Solano E, Ceperuelo-Mallafré V, Hernández P, Wabitsch M, Vendrell J 


Markers of monocyte activation revealed by lipidomic profiling of arachidonic acid-containing phospholipids 

Balgoma D, Astudillo AM, Pérez-Chacón G, Montero O, Balboa MA, Balsinde J 


Maternal undernutrition increases pancreatic IGF-2 and partially suppresses the physiological wave of {beta}-cell 

apoptosis during the neonatal period 

de Miguel-Santos L, Fernández-Millán E, Angeles Martín M, Escrivá F, Alvarez C 

J Mol Endocrinol, 44, 25-36 (2010) 

Metabolic fingerprints of proliferative diabetic retinopathy: an 1H-NMR-based metabonomic approach using vitreous humor 

Barba I, Garcia-Ramírez M, Hernández C, Alonso MA, Masmiquel L, García-Dorado D, Simó R 

Invest Ophthalmol Vis Sci, 51, 4416-4421 (2010) 

Metabolomic assessment of the effect of dietary cholesterol in the progressive development of fatty liver disease 

Vinaixa M, Rodríguez MA, Rull A, Beltrán R, Bladé C, Brezmes J, Cañellas N, Joven J, Correig X 

J Proteome Res, 9, 2527-2538 (2010) 

Minimal state models for ionic channels involved in glucagon secretion 

Gonzalez-Velez V, Gil A, Quesada I 

Math Biosci Eng, 7, 793-807 (2010) 

Mitochondrial fusion proteins: dual regulators of morphology and metabolism 

Zorzano A, Liesa M, Sebastián D, Segalés J, Palacín M 

Semin Cell Dev Biol, 21, 566-574 (2010) Review 

Neonatal diabetes caused by mutations in sulfonylurea receptor 1: interplay between expression and Mg-nucleotide 

gating defects of ATP-sensitive potassium channels 

Zhou Q, Garin I, Castaño L, Argente J, Muñoz-Calvo MT, Perez de Nanclares G, Shyng SL 

J Clin Endocrinol Metab, 95, E473-478 (2010) 

New pathogenic candidates for diabetic macular edema detected by proteomic analysis 

Hernández C, García-Ramírez M, Colomé N, Villarroel M, Corraliza L, García-Pacual L, Casado J, Canals F, Simó R 

Diabetes Care, 33, e92 (2010) 

Nitric oxide repression of Nanog promotes mouse embryonic stem cell differentiation 

Mora-Castilla S, Tejedo JR, Hmadcha A, Cahuana GM, Martín F, Soria B, Bedoya FJ 

Cell Death Differ, 17, 1025-1033 (2010) 

Normal proliferation and tumorigenesis but impaired pancreatic function in mice lacking the cell cycle regulator sei1 

Fernandez-Marcos PJ, Pantoja C, Gonzalez-Rodriguez A, Martin N, Flores JM, Valverde AM, Hara E, Serrano M 


Nutritional regulation of interleukin-6 release from adipocytes 

García-Escobar E, Rodríguez-Pacheco F, García-Serrano S, Gómez-Zumaquero JM, Haro-Mora JJ, Soriguer F, Rojo- 

Martínez G 


138 CibeRdem

Obesity and insulin resistance-related changes in the expression of lipogenic and lipolytic genes in morbidly obese subjects 

Tinahones FJ, Garrido-Sanchez L, Miranda M, García-Almeida JM, Macias-Gonzalez M, Ceperuelo V, Gluckmann E, 

Rivas-Marin J, Vendrell J, García-Fuentes E 


Obesity impairs general health-related quality of life (HR-QoL) in premenopausal women to a greater extent than 

polycystic ovary syndrome (PCOS) 

Alvarez-Blasco F, Luque-Ramírez M, Escobar-Morreale HF 


Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaén and Córdoba 

(Spain) 2008 

López-Miranda J, Pérez-Jiménez F, Ros E, De Caterina R, Badimón L, Covas MI, Escrich E, Ordovás JM, Soriguer F, Abiá R, 

de la Lastra CA, Battino M, Corella D, Chamorro-Quirós J, Delgado-Lista J, Giugliano D, Esposito K, Estruch R, Fernandez- 

Real JM, Gaforio JJ, La Vecchia C, Lairon D, López-Segura F, Mata P, Menéndez JA, Muriana FJ, Osada J, Panagiotakos 

DB, Paniagua JA, Pérez-Martinez P, Perona J, Peinado MA, Pineda-Priego M, Poulsen HE, Quiles JL, Ramírez-Tortosa MC, 

Ruano J, Serra-Majem L, Solá R, Solanas M, Solfrizzi V, de la Torre-Fornell R, Trichopoulou A, Uceda M, Villalba-Montoro 

JM, Villar-Ortiz JR, Visioli F, Yiannakouris N 


Overexpression of kinase-negative protein kinase Cdelta in pancreatic beta-cells protects mice from diet-induced glucose 

intolerance and beta-cell dysfunction 

Hennige AM, Ranta F, Heinzelmann I, Düfer M, Michael D, Braumüller H, Lutz SZ, Lammers R, Drews G, Bosch F, Häring 

HU, Ullrich S 


Paired subcutaneous and visceral adipose tissue aquaporin-7 expression in human obesity and type 2 diabetes: 

differences and similarities between depots 

Miranda M, Escoté X, Ceperuelo-Mallafré V, Alcaide MJ, Simón I, Vilarrasa N, Wabitsch M, Vendrell J 


Pancreas and kidney transplantation: long-term endocrine function 

Mora M, Ricart MJ, Casamitjana R, Astudillo E, López I, Jiménez A, Fernández-Cruz L, Esmatjes E 

Clin Transplant, 24, E236-E240 (2010) 

Pancreatic islet cells: a model for calcium-dependent peptide release 

Soria B, Tuduri E, Gonzalez A, Hmadcha A, Martin F, Nadal A, Quesada I 


Pitavastatin - from clinical trials to clinical practice 

Masana L 

Atheroscler Suppl, 11, 15-22 (2010) Review 

Placental FTO expression relates to fetal growth 

Bassols J, Prats-Puig A, Vázquez-Ruíz M, García-González MM, Martínez-Pascual M, Avellí P, Martínez-Martínez R, 

Fàbrega R, Colomer-Virosta C, Soriano-Rodríguez P, Díaz M, de Zegher F, Ibánez L, López-Bermejo A 


Plasma homocysteine levels are associated with ulceration of the foot in patients with type 2 diabetes mellitus 

González R, Pedro T, Real JT, Martínez-Hervás S, Abellán MR, Lorente R, Priego A, Catalá M, Chaves FJ, Ascaso JF, 

Carmena R 


Polyunsaturated fatty acids down-regulate in vitro expression of the key intestinal cholesterol absorption protein NPC1L1: 

no effect of monounsaturated nor saturated fatty acids 


139

Alvaro A, Rosales R, Masana L, Vallvé JC 

J Nutr Biochem, 21, 518-525 (2010) 

Position paper: Rapid responses to steroids: current status and future prospects 

Wendler A, Baldi E, Harvey BJ, Nadal A, Norman A, Wehling M 

Eur J Endocrinol, 162, 825-830 (2010) Editorial 

PPARgamma expression after a high-fat meal is associated with plasma superoxide dismutase activity in morbidly obese 

persons 

Garcia-Fuentes E, Murri M, Garrido-Sanchez L, Garcia-Serrano S, García-Almeida JM, Moreno-Santos I, Tinahones FJ, 

Macias-Gonzalez M 

Obesity (Silver Spring), 18, 952-958 (2010) 

PP2A regulatory subunit PP2A-B’ counteracts S6K phosphorylation 

Hahn K, Miranda M, Francis VA, Vendrell J, Zorzano A, Teleman AA 


Production, purification and characterization of adeno-associated vectors 

Ayuso E, Mingozzi F, Bosch F 

Curr Gene Ther, 10, 423-436 (2010) Review 

Progress in understanding postprandial dyslipidaemia: Second International Symposium on the Role of Chylomicrons in 

Disease l 

Watts GF, Ribalta J 

Atheroscler Suppl, 11, 1-2 (2010) Editorial 

Proof-of-concept trial on the efficacy of sodium tungstate in human obesity 

Hanzu F, Gomis R, Coves MJ, Viaplana J, Palomo M, Andreu A, Szpunar J, Vidal J 

Diabetes Obes Metab, 12, 1013-1018 (2010) 

Protein intake, body composition, and protein status following bariatric surgery 

Andreu A, Moizé V, Rodríguez L, Flores L, Vidal J 


Proteomic analysis of plasma in the polycystic ovary syndrome identifies novel markers involved in iron metabolism, 

acute-phase response, and inflammation 

Insenser M, Martínez-García MA, Montes R, San-Millán JL, Escobar-Morreale HF 


PTP1B deficiency enhances liver growth during suckling by increasing the expression of insulin-like growth 

factor-I 

Escrivá F, González-Rodriguez A, Fernández-Millán E, Rondinone CM, Alvarez C, Valverde AM 


Pubertal metformin therapy to reduce total, visceral, and hepatic adiposity 

Ibáñez L, Lopez-Bermejo A, Diaz M, Marcos MV, de Zegher F 

J Pediatr, 156, 98-102e1 (2010) 

Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis 

Garin I, Edghill EL, Akerman I, Rubio-Cabezas O, Rica I, Locke JM, Maestro MA, Alshaikh A, Bundak R, del Castillo G, 

Deeb A, Deiss D, Fernandez JM, Godbole K, Hussain K, O’Connell M, Klupa T, Kolouskova S, Mohsin F, Perlman K, Sumnik 

Z, Rial JM, Ugarte E, Vasanthi T; Neonatal Diabetes International Group, Johnstone K, Flanagan SE, Martínez R, Castaño 

C, Patch AM, Fernández-Rebollo E, Raile K, Morgan N, Harries LW, Castaño L, Ellard S, Ferrer J, Perez de Nanclares G, 

Hattersley AT 


140 CibeRdem

Reduced insulin secretion in protein malnourished mice is associated with multiple changes in the beta-cell stimulussecretion 

coupling 

Soriano S, Gonzalez A, Marroquí L, Tudurí E, Vieira E, Amaral AG, Batista TM, Rafacho A, Boschero AC, Nadal A, Carneiro 

EM, Quesada I 


Regeneration of insulin production by autologous bone marrow blood autotransplantation in patients with type 1 diabetes 

Esmatjes E, Montaña X, Real MI, Blanco J, Conget I, Casamitjana R, Rovira M, Gomis R, Marin P 


Relation between human LPIN1, hypoxia and endoplasmic reticulum stress genes in subcutaneous and visceral adipose tissue 

Miranda M, Escoté X, Ceperuelo-Mallafré V, Megía A, Caubet E, Näf S, Gómez JM, González-Clemente JM, Vicente V, 

Vendrell J 


Role of the TSC1-TSC2 complex in the integration of insulin and glucose signaling involved in pancreatic beta-cell 

proliferation 

Bartolomé A, Guillén C, Benito M 


Signaling and biological effects of glucagon-like peptide 1 on the differentiation of mesenchymal stem cells from human 

bone marrow 

Sanz C, Vázquez P, Blázquez C, Barrio PA, Alvarez M del M, Blázquez E 


Signaling role for lysophosphatidylcholine acyltransferase 3 in receptor-regulated arachidonic acid reacylation reactions in 

human monocytes 

Pérez-Chacón G, Astudillo AM, Ruipérez V, Balboa MA, Balsinde J 


Skeletal muscle metabolism in the pathology and treatment of type 1 diabetes 

Mann CJ, Ayuso E, Anguela XM, Bosch F 

Curr Pharm Des, 16, 1002-1020 (2010) Review 

Soluble fibre (Plantago ovata husk) reduces plasma low-density lipoprotein (LDL) cholesterol, triglycerides, insulin, 

oxidised LDL and systolic blood pressure in hypercholesterolaemic patients: A randomised trial 

Solà R, Bruckert E, Valls RM, Narejos S, Luque X, Castro-Cabezas M, Doménech G, Torres F, Heras M, Farrés X, Vaquer 

JV, Martínez JM, Almaraz MC, Anguera A 


Subjects with early-onset type 2 diabetes show defective activation of the skeletal muscle PGC-1{alpha}/Mitofusin-2 

regulatory pathway in response to physical activity 

Hernández-Alvarez MI, Thabit H, Burns N, Shah S, Brema I, Hatunic M, Finucane F, Liesa M, Chiellini C, Naon D, Zorzano 

A, Nolan JJ 


Switching to once-daily liraglutide from twice-daily exenatide further improves glycemic control in patients with type 2 

diabetes using oral agents 

Buse JB, Sesti G, Schmidt WE, Montanya E, Chang CT, Xu Y, Blonde L, Rosenstock J; Liraglutide Effect Action in Diabetes-6 

Study Group 


The APOA5-1131 T>C variant enhances the association between RBP4 and hypertriglyceridemia in diabetes 

Cabré A, Lázaro I, Girona J, Manzanares JM, Marimón F, Plana N, Guardiola M, Heras M, Masana L 



141

The apolipoprotein A5 (APOA5) gene predisposes Caucasian children to elevated triglycerides and vitamin E (Four 

Provinces Study) 

Guardiola M, Ribalta J, Gómez-Coronado D, Lasunción MA, de Oya M, Garcés C 


The atrial natriuretic peptide and guanylyl cyclase-A system modulates pancreatic beta-cell function 

Ropero AB, Soriano S, Tudurí E, Marroquí L, Téllez N, Gassner B, Juan-Picó P, Montanya E, Quesada I, Kuhn M, Nadal A 


The cationic cluster of group IVA phospholipase A2 (Lys488/Lys541/Lys543/Lys544) is involved in translocation of the 

enzyme to phagosomes in human macrophages 

Casas J, Valdearcos M, Pindado J, Balsinde J, Balboa MA 


The determinants of insulin sensitivity, β-cell function, and glucose tolerance are different in patients with polycystic ovary 

syndrome than in women who do not have hyperandrogenism 

Luque-Ramírez M, Alpañés M, Escobar-Morreale HF 

Fertil Steril, 94, 2214-2221 (2010) 

The first clinical case of a mutation at residue K185 of Kir6.2 (KCNJ11): a major ATP-binding residue 

Shimomura K, de Nanclares GP, Foutinou C, Caimari M, Castaño L, Ashcroft FM 


The nuclear cofactor DOR regulates autophagy in mammalian and Drosophila cells 

Mauvezin C, Orpinell M, Francis VA, Mansilla F, Duran J, Ribas V, Palacín M, Boya P, Teleman AA, Zorzano A 

EMBO Rep, 11, 37-44 (2010) 

The obese healthy paradox: is inflammation the answer? 

Barbarroja N, López-Pedrera R, Mayas MD, García-Fuentes E, Garrido-Sánchez L, Macías-González M, El Bekay R, Vidal- 

Puig A, Tinahones FJ 

Biochem J, 430, 141-149 (2010) 

The p65 subunit of NF-kappaB binds to PGC-1alpha, linking inflammation and metabolic disturbances in 

cardiac cells 

Alvarez-Guardia D, Palomer X, Coll T, Davidson MM, Chan TO, Feldman AM, Laguna JC, Vázquez-Carrera M 

Cardiovasc Res, 87, 449-458 (2010) 

The relationships between IGF-1 and CRP, NO, leptin, and adiponectin during weight loss in the morbidly obese 

Pardina E, Ferrer R, Baena-Fustegueras JA, Lecube A, Fort JM, Vargas V, Catalán R, Peinado-Onsurbe J 


The role of genetic variation in peroxisome proliferator-activated receptors in the polycystic ovary syndrome (PCOS): an 

original case-control study followed by systematic review and meta-analysis of existing evidence 

San-Millán JL, Escobar-Morreale HF 


The role of transmembrane protein 27 (TMEM27) in islet physiology and its potential use as a beta cell mass 

biomarker 

Altirriba J, Gasa R, Casas S, Ramírez-Bajo MJ, Ros S, Gutierrez-Dalmau A, Ruiz de Villa MC, Barbera A, Gomis R 


The suppressor of cytokine signalling 2 (SOCS2) is a key repressor of insulin secretion 

Lebrun P, Cognard E, Gontard P, Bellon-Paul R, Filloux C, Berthault MF, Magnan C, Ruberte J, Luppo M, Pujol A, Pachera 

N, Herchuelz A, Bosch F, Van Obberghen E 


142 CibeRdem

Treatment of polycystic ovary syndrome (PCOS) with metformin ameliorates insulin resistance in parallel with the decrease 

of serum interleukin-6 concentrations 

Luque-Ramírez M, Escobar-Morreale HF 

Horm Metab Res, 42, 815-820 (2010) 

Tumor necrosis-like weak inducer of apoptosis as a proinflammatory cytokine in human adipocyte cells: up-regulation in 

severe obesity is mediated by inflammation but not hypoxia 

Vendrell J, Maymó-Masip E, Tinahones F, García-España A, Megia A, Caubet E, García-Fuentes E, Chacón MR 


Type 2 diabetes impairs pulmonary function in morbidly obese women: a case-control study 

Lecube A, Sampol G, Muñoz X, Hernández C, Mesa J, Simó R 


Weight loss in prepubertal obese children is associated with a decrease in adipocyte fatty-acid-binding protein without 

changes in lipocalin-2: a 2-year longitudinal study 

Corripio R, Gónzalez-Clemente JM, Pérez-Sánchez J, Näf S, Gallart L, Nosàs R, Vendrell J, Caixàs A 


WWOX gene is associated with HDL cholesterol and triglyceride levels 

Sáez ME, González-Pérez A, Martínez-Larrad MT, Gayán J, Real LM, Serrano-Ríos M, Ruiz A 

BMC Med Genet, 11, 148 (2010) 


143

www.ciberdem.org/annualreport 

CIBERDEM 


Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders 

Scientific Director Ramon Gomis 

Adjunct Scientific Director Anna Novials 

Steering Committee Ramon Gomis, Anna Novials, Manuel Benito, Rafael Carmena, Fàtima Bosch, Antonio Zorzano 

Management Office 

Managing Director | Ana Bosch 

Executive Secretary | Tania Fernández 

Human Resources and Legal Manager | Libertad Montaño 

Project Manager | Gemma Pascual 

Knowledge Management and Communication | Marta Vidal 

Fundraising and Marketing | Johanna Rivera 

Proposal Writer | Donald Mc Donagh 

Accounting Agent | Antonio Santaliestra 

Purchase Agent | Sebastián Montaño 

Administrative Assistant | Maria Rosa Vázquez 

Contact details | Bonanova 69, 6th floor, 08017 Barcelona, Spain, info@ciberdem.org 

An initiative of ISCIII 

Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Gobierno de España 

Iniciativa Ingenio 2010, programa Consolider, Acciones CIBER 

VI Plan Nacional de I+D+i 2008-2011 

Institutions of the Consortium 

BIOEF (Fundación Vasca de Innovación e Investigación Sanitarias), CIPF (Fundación Centro de Investigación Príncipe Felipe), CSIC 

(Consejo Superior de Investigaciones Científicas), FIHCUV (Fundación Investigación Hospital Clínico Universitario de Valencia), FIR-HUVH 

(Fundació Institut de Recerca Hospital Universitari Vall d’Hebron), FJD (Fundación Jiménez Díaz), FSJD (Fundació Sant Joan de Déu), 

IDIBAPS (Institut d’Investigacions Biomèdiques August Pi i Sunyer), IDIBELL (Fundació Institut d’Investigació Biomèdica de Bellvitge), IISPV 

(Fundació Institut d’Investigació Sanitària Pere Virgili), IMABIS (Fundación Instituto Mediterráneo para el Avance de la Biotecnología y la 

Investigación Sanitaria), IRB (Fundació Institut de Recerca Biomèdica), IRHSCSP (Institut de Recerca Hospital de la Santa Creu i Sant 

Pau), SERMAS (Servicio Madrileño de Salud), UAB (Universitat Autònoma de Barcelona), UB (Universitat de Barcelona), UCM (Universidad 

Complutense de Madrid), UMH (Universidad Miguel Hernández), UPO (Universidad Pablo de Olavide) 

2011 CIBERDEM 

Edition | CIBERDEM Management Office 

Director | Ramon Gomis 

Editor | Marta Vidal 

Designer | Octavi Rodríguez 

Language Consultant | Andrew Hastings 

Texts | CIBERDEM Research Groups and CIBERDEM Management Office 

Images and Graphics | Manuel Acosta, Verónica Alba, Gemma Alberich, Carmen Álvarez, David Álvarez, Elvira Álvarez, Francesc Avia, 

María Ángeles Balboa, Jesús Balsinde, Alberto Bartolomé, Francisco Blanco Vaca, Enrique Blázquez, Fàtima Bosch Group, Laura Brugnara, 

Ernesto Caballero, Ivan Caravaca, Manuel Carrasco, Xavier Correig, Adelaida Díaz, Héctor F Escobar Morreale, Arturo Fernández, Raimon 

Ferré, Mónica Fontela, Lucía García, Intza Garin, Ramon Gomis Group, Irene Gutiérrez, Hospital de Cruces, Hospital Universitari de Bellvitge, 

Verónica Hurtado, Lourdes Ibáñez, María Rosa Insenser, IRB Barcelona, Miguel Ángel Maestro, Roger Mallol, María Luisa Mansego, Franz 

Martín, Ángela Martínez Valverde, Isabel Martorell, Metabolomics Platform, Mercedes Miranda, Sonsoles Morcillo, Paola Moreno, Emma 

Mormeneo, Juan Pablo Muñoz, Luke Noon, Katerina Papageorgiou, Vanessa Prensa, Johanna Rivera, Octavi Rodríguez, Anabel Rojas, 

Gemma Rojo, Isabel Roncero, Susana Ros, José Luis San Millán, Beatriz Sánchez, María del Carmen Sanz, Manuel Serrano Ríos, Noèlia 

Téllez, Ricardo Uña, Mario Vallejo, Manuel Vázquez Carrera, Patricia Vázquez, Marta Villarroel, Maria Vinaixa, Carina Zabena 

Cover image | Ana B Ropero by CIBERDEM 

3-D reconstruction of a pancreatic islet of Langerhans 

loaded with the calcium-sensitive dye, Fluo-4. Blue color 

indicates low intracellular calcium concentration, 

while orange and yellow indicate high calcium. 

http://creativecommons.org/licenses/by-nc-nd/3.0 

Special thanks to all those individuals and institutions without whose cooperation and good will this book would not have been possible.

CIBERDEM, the Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, began 

its activity over three years ago and it is now time to take stock of its achievements. Some are already evident 

and among these is the qualitative leap forward as regards the number and excellence of publications. To this 

success we should add others such as the ability of groups to work together, especially in the case of clinical 

and basic research groups, which is a clear indication of our strong commitment to translational research, as 

well as an obvious demonstration that these associations between groups are advantageous when it comes to 

obtaining funding. All of this will soon allow us to put CIBERDEM firmly on the map of competitive biomedical 

research in Europe. Ramon Gomis, CIBERDEM Scientific Director

2010 AnnuAl REpoRT - Ciberdem

Create successful ePaper yourself

Delete template?

Save as template?