Investigation for intracellular mechanisms of pancreatic-cell proliferation and anti-apoptotic effect of incretin

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Endoplasmic reticulum stress(ERS) is one of the contributing factors in the development of type 2 diabetes. Exendin-4(Ex-4), a potent GLP-1 receptor agonist, significantly reduced blood glucose levels and preservedυ-cell mass and the number of islets in Akita mice, an animal model of ER stress-mediated diabetes. Since there was no such effect observed in the mice treated with phlorizin, an insulin-independent glucose-lowering drug, the effects were suggested to be independent of glucose-lowering effect of Ex-4. Akita mice treated with Ex-4 showed a significant decrease in apoptosis ofυ-cells and significantly reduced CHOP mRNA and protein levels inυ-cells, suggesting thatυ-cell protective effects of Ex-4 were achieved mainly through a reduction of ER stress-mediatedυ-cell damage and apoptotic cell death.