二肽基肽酶-4抑制剂影响胰岛β细胞机制的研究进展

Research progress of mechanism of the effect of DPP-4 inhibitors on pancreatic beta cells

二肽基肽酶-4(DPP-4)抑制剂减轻内质网负担和线粒体氧化应激,进而促进胰岛β细胞增殖分化;上调抗氧化应激相关的基因,如Cat、Gpxt及Sod2等,抑制硝基酪氨酸生成;下调脂质合成的基因表达,降低血载脂蛋白B、LDL-C、TG、TC和FFA水平;下调一氧化氮(NO)和TNF-α等炎症因子的浓度;刺激胰岛β细胞分泌胰淀素,但不会促进其的沉积,且对胰淀素所引起的胰岛β细胞的丧失有保护作用;从而改善了胰岛β细胞功能,增加了其质量,延缓了其衰竭。

DPP-4 inhibitors can alleviate the endoplasmic reticulum stress and mitochondrial oxidative stress to promote the proliferation and differentiation of beta-cells; up-regulate anti-oxidative stress genes,such as Cat,Gpxt and Sod2,and inhibit the production of nitrotyrosine; down-regulate the expression of lipid synthesis genes,and reduce levels of apolipoprotein B,low density lipoprotein,triglycerides,total cholesterol,and free fatty acids; reduce concentrations of inflammatory cytokines like NO and TNF-α; stimulate pancreatic beta-cells to secrete amylin without promoting its deposition,and have protective function for the loss of pancreatic beta cells caused by amylin; therefore improve the function of pancreatic beta cells,increase their mass,and delay their failure.