SGLT2抑制剂对胰岛β细胞的保护作用及潜在机制
Protective effects and potential mechanism of the SGLT2 inhibitor on islet β cells
摘要保护胰岛β细胞是糖尿病治疗的重要策略。新型降糖药物钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂通过抑制肾小管对葡萄糖的重吸收来降低血糖,该降糖作用不依赖胰岛素。多项临床研究发现,该类药物可明显改善β细胞功能。动物研究显示,SGLT2抑制剂可增加β细胞总量。SGLT2抑制剂促进β细胞再生有以下几种方式:促进β细胞增殖、抑制β细胞凋亡和去分化、促进α细胞向β细胞转化及诱导前体细胞来源的β细胞新生。降糖、减重、改善血脂谱等机体代谢改善的间接作用、抑制炎症反应、促进胰岛α细胞分泌GLP-1、调控胰岛基因表达等可能介导了SGLT2抑制剂对β细胞的保护。
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abstractsIslet β cell protection is one of the key strategies for diabetes treatment. The new antidiabetic drug sodium-glucose cotransporter 2(SGLT2)inhibitor decreases blood glucose by inhibiting glucose reabsorption in the renal tubule, independent of insulin. Various clinical studies have shown that SGLT2 inhibitors improve β cell function. Furthermore, animal experiments have indicated that SGLT2 inhibitors increase β cell mass. SGLT2 inhibitors promote islet regeneration through stimulating β cell proliferation, inhibiting β cell apoptosis and dedifferentiation, enhancing transdifferentiation of α cells to β cells, and initiating progenitor-derived β cell neogenisis. Indirect effects of metabolic improvement(i.e.lowering glucose, losing weight, improving lipid metabolism), inhibiting inflammatory reaction, inducing glucagon-like peptide-1 secreted from α cells, and regulating gene changes might be involved in the β cell protection of SGLT2 inhibitors.
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