2010 AnnuAl REpoRT - Ciberdem

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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 2010 Annual Report 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 Total IF: 4.752 Publications: 1, in the first quartile Research grants: 2 National projects: 1 Autonomous Community projects: 1 Scientific collaborations within CIBERDEM: 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
Page 1 and 2: 2010 Annual Report CIBERDEM Centro
Page 4 and 5: Letter from the Scientific Director
Page 6 and 7: Contents Prologue Research results
Page 8 and 9: Research results Publications In 20
Page 10 and 11: Project management Introduction The
Page 12 and 13: Training programme Introduction The
Page 14 and 15: Outreach activities CIBERDEM Fundra
Page 16 and 17: More about CIBERDEM The Centro de I
Page 18 and 19: Human Resources In 2010, CIBERDEM h
Page 20 and 21: Transversal projects Di@bet.es Stud
Page 22 and 23: Di@bet.es Study Introduction Attemp
Page 24 and 25: CIBERDEM Projects Introduction CIBE
Page 26 and 27: girls (girls born small for gestati
Page 28 and 29: Biobank Introduction and objectives
Page 30 and 31: Metabolomics Platform Introduction
Page 33: Area 1 Insulin signalling and resis
Page 37 and 38: Metabolomics Platform Universitat R
Page 39 and 40: Obesity, inflammation and insulin r
Page 41 and 42: Mechanisms of control of glucose an
Page 43 and 44: Metabolic engineering and diabetes
Page 45 and 46: Molecular mechanisms of insulin res
Page 47 and 48: Molecular characteristics, and acti
Page 49 and 50: Heterogenic and polygenic diseases.
Page 51: Principal Investigator: Antonio Zor
Page 54 and 55: The research activity of this area
Page 56 and 57: The cationic cluster of group IVA p
Page 58 and 59: agent that affects the enterohepati
Page 60 and 61: Dyslipidaemia, inflammation and end
Page 62 and 63: Daño orgánico en la diabetes mell
Page 64 and 65: Proteomic analysis of plasma in the
Page 66 and 67: Prenatal growth restriction and sub
Page 68 and 69: The effects of metformin on cardiov
Page 70 and 71: Lipids and Arteriosclerosis Researc
Page 72 and 73: Review Pitavastatin - from clinical
Page 74 and 75: Diabetobe Hospital Clínico San Car
Page 76 and 77: Scientific collaborations within CI
Page 78 and 79: Atherosclerosis, 209, 201-205 (2010
Page 80 and 81: Solvay, SA: 2008-2010 Principal Inv
Page 82 and 83: Endocrinology and Nutrition Service
Page 84 and 85:
Prevención de la Diabetes mellitus
Page 86 and 87:
Pharmacological targets in inflamma
Page 88 and 89:
Diabetes and Metabolic Associated D
Page 90 and 91:
Autonomous Community project Grup d
Page 92 and 93:
Area 3 of CIBERDEM comprises thirte
Page 94 and 95:
Escrivá F, Alvarez C J Mol Endocri
Page 96 and 97:
Am J Physiol Endocrinol Metab, 298,
Page 98 and 99:
Transgenic animal models and gene t
Page 100 and 101:
Ayuso E, Mingozzi F, Bosch F Curr G
Page 102 and 103:
Laboratory of Molecular Endocrinolo
Page 104 and 105:
Hospital de Cruces Diabetes Researc
Page 106 and 107:
Research grants International proje
Page 108 and 109:
Proinsulin and tyrosine hydroxilase
Page 110 and 111:
Genomic programming of beta cells I
Page 112 and 113:
Diabetes and obesity: biopathology
Page 114 and 115:
Utilidad de la ecografía arterial
Page 116 and 117:
Islet cell and stem cell physiology
Page 118 and 119:
in diabetic patients with chronic c
Page 120 and 121:
Liraglutide versus sitagliptin for
Page 122 and 123:
Unit of Cell Physiology and Nutriti
Page 124 and 125:
National projects Efectos a corto y
Page 126 and 127:
Altirriba J, Gasa R, Casas S, Ramí
Page 128 and 129:
Transcriptional mechanisms of pancr
Page 131 and 132:
Epilogue
Page 133 and 134:
Keyword index* Beta-cell signal tra
Page 135 and 136:
Association of selected ABC gene fa
Page 137 and 138:
Leiter LA, Levitt NS, Mareev V, Mar
Page 139 and 140:
Low body adiposity and high leptine
Page 141 and 142:
Alvaro A, Rosales R, Masana L, Vall
Page 143 and 144:
The apolipoprotein A5 (APOA5) gene
Page 145 and 146:
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2010 AnnuAl REpoRT - Ciberdem

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