Expression data from fresh and cultured islets at different glucose concentrations

-cell identity is determined by tightly regulated transcriptional networks that are modulated by extracellular cues, thereby ensuring -cell adaptation to the organisms 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 -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 (- 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.

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Moreno-Asso A, Castaño C, Grilli A, Novials A, Servitja JM