review of literature on clinical pancreatology - The Pancreapedia

preparations. They were also employed to show that human islet expansion culturesoriginated from nonendocrine cells and that insulin expression levels could be increased toup to 1 percent <strong>of</strong> normal islet cells by subpopulation sorting and overexpression <strong>of</strong> thetranscription factors Pdx-1 and ngn3, an improvement over previous results with this culturesystem. These methods permit the analysis and isolation <strong>of</strong> functionally distinct pancreaticcell populations with potential for cell therapy [111].OxygenBeyond its role as an electron acceptor in aerobic respiration, oxygen is also a key effector <strong>of</strong>many developmental events. The oxygen-sensing machinery and the very fabric <strong>of</strong> cellidentity and function have been shown to be deeply intertwined. Here it was taken a first lookat how oxygen might lie at the crossroads <strong>of</strong> at least two <strong>of</strong> the major molecular pathwaysthat shape pancreatic development. Based on recent evidence and a thorough <strong>review</strong> <strong>of</strong> the<strong>literature</strong>, it was presented a theoretical model whereby evolving oxygen tensions mightchoreograph to a large extent the sequence <strong>of</strong> molecular events resulting in the development<strong>of</strong> the organ. In particular, it was proposed that lower oxygenation prior to the expansion <strong>of</strong>the vasculature may favour HIF (hypoxia inducible factor)-mediated activation <strong>of</strong> Notch andrepression <strong>of</strong> Wnt/beta-catenin signalling, limiting endocrine cell differentiation. With thedevelopment <strong>of</strong> vasculature and improved oxygen delivery to the developing organ, HIFmediatedsupport for Notch signalling may decline while the beta-catenin-directed Wntsignalling is favoured, which would support endocrine cell differentiation and perhapsexocrine cell proliferation/differentiation [112].Thyrotropin-releasing hormoneThyrotropin-releasing hormone (TRH) is expressed in rodent and human adult pancreata andin mouse pancreas during embryonic development. However, expression <strong>of</strong> TRH receptors(TRHRs) in the pancreas is controversial. It was used quantitative reverse transcriptionpolymerasechain reaction to measure TRH and TRHR messenger RNA (mRNA). To studythe effects <strong>of</strong> TRHR expression in a pancreatic progenitor population, it was expressedTRHRs in human islet-derived precursor cells (hIPCs) by infection with adenoviral vectorAdCMVmTRHR. Thyrotropin-releasing hormone receptor signaling was measured as inositolphosphate production and intracellular calcium transients. Thyrotropin-releasing hormonereceptor expression was measured by [3H]methyl-TRH binding. Apoptosis was monitored byrelease <strong>of</strong> cytochrome c from mitochondria. It was shown that TRH mRNA is expressed inhuman fetal and adult pancreata, and that TRHR mRNA is expressed in fetal humanpancreas but not in adult human pancreas. Thyrotropin-releasing hormone receptorsexpressed in hIPCs were shown to signal normally. Most importantly, TRH treatment forseveral days stimulated apoptosis in hIPCs expressing approximately 400,000 TRHRs percell. These findings suggest a possible role for TRH/TRHR signaling in pancreatic precursorsto promote programmed cell death, a normal constituent <strong>of</strong> morphogenesis during embryonicdevelopment in humans [113].Pancreatic anatomy and malformationsEctopic pancreasTo describe the computed tomographic (CT) findings <strong>of</strong> ectopic pancreas and to identify thefeatures that differentiate it from other similarly manifesting gastric submucosal tumors suchas gastrointestinal stromal tumor (GIST) and leiomyoma, which are the most commongastrointestinal submucosal tumors a retrospective study investigated CT images <strong>of</strong>pathologically proved ectopic pancreases (n=14), GISTs (n=33), and leiomyomas (n=7) in