BioProject

β-cell identity is determined by tightly regulated transcriptional networks that are modulated by extracellular cues, thereby ensuring β-cell adaptation to the organism’s insulin demands. More...

β-cell identity is determined by tightly regulated transcriptional networks that are modulated by extracellular cues, thereby ensuring β-cell adaptation to the organism’s insulin demands. We have observed in pancreatic islets that stimulatory glucose concentrations induced a gene profile that was similar to that of freshly isolated islets, indicating that glucose-elicited cues are involved in maintaining β-cell identity. Low glucose induces the expression of ubiquitous genes involved in stress responses, nutrient sensing, and organelle biogenesis. By contrast, stimulatory glucose concentrations activate genes with a more restricted expression pattern (β- and neuronal- cell identity). Consistently, glucose-induced genes are globally reduced in islets deficient with Hnf1a (MODY3), characterized by a deficient glucose metabolism. Of interest, a cell cycle gene module was the most enriched among the variable genes between intermediate and stimulatory glucose concentrations. Glucose regulation of the islet transcriptome was unexpectedly broadly maintained in islets from aged mice. However, the cell cycle gene module is selectively lost in old islets and the glucose activation of this module is not recovered even in the absence of the cell cycle inhibitor p16. We used microarrays to detail the global programme of gene expression regulated by glucose in young and aged pancreatic islets as well as freshly-isolated islets. Overall design: Pancreatic islets from young and old mice were isolated and cultured at different glucose concentrations for RNA extraction and hybridization on Affymetrix microarrays. Islets were cultured at 3mM (G3), 5.5mM (G5), 11mM (G11) and 16mM (G16). Freshly-isolated islets (F) were also processed for RNA extraction . We also assessed the dynamic glucose regulation of gene expression at different time-points after an overnight at 3mM (T0): after 1h at 11mM (T1) and after 4h (T4). Less...