Vildagliptin preserves the mass and function of pancreatic beta cells via the developmental regulation and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes

作者：Hamamoto S; Kanda Y; Shimoda M; Tatsumi F; Kohara K; Tawaramoto K; Hashiramoto M; Kaku K^*

来源：Diabetes, Obesity and Metabolism, 2013, 15(2): 153-163.

DOI：10.1111/dom.12005

• ss cell
• DPP-IV inhibitor
• incretins

Aim We investigated the molecular mechanisms by which vildagliptin preserved pancreatic beta cell mass and function. Methods Morphological, biochemical and gene expression profiles of the pancreatic islets were investigated in male KK-Ay-TaJcl(KK-Ay) and C57BL/6JJcl (B6) mice aged 8?weeks which received either vildagliptin or a vehicle for 4?weeks. Results Body weight, food intake, fasting blood glucose, plasma insulin and active glucagon-like peptide-1 were unchanged with vildagliptin treatment in both mice. In KK-Ay mice treated with vildagliptin, increased plasma triglyceride (TG) level and islet TG content were decreased, insulin sensitivity significantly improved, and the glucose tolerance ameliorated with increases in plasma insulin levels. Furthermore, vildagliptin increased glucose-stimulated insulin secretion, islet insulin content and pancreatic beta cell mass in both strains. By vildagliptin, the expression of genes involved in cell differentiation/proliferation was upregulated in both strains, those related to apoptosis, endoplasmic reticulum stress and lipid synthesis was decreased and those related to anti-apoptosis and anti-oxidative stress was upregulated, in KK-Ay mice. The morphological results were consistent with the gene expression profiles. Conclusion Vildagliptin increases beta cell mass by not only directly affecting cell kinetics but also by indirectly reducing cell apoptosis, oxidative stress and endoplasmic reticulum stress in diabetic mice.

• 出版日期2013-2