The main pathogenesis of type 1 diabetes mellitus (T1DM) is autoimmune-mediated apoptosis of pancreatic islet β cells. We sought to characterize the function of microRNA-203a (miR-203a) on pancreatic islet β cell proliferation and apoptosis. In situ hybridization was used to detect the expression of miR-203a in islet β cells in normal and hyperglycaemic non-obese diabetic (NOD) mice. Cell proliferation was measured by cell counting kit eight and cell apoptosis was detected using flow cytometry. Insulin receptor substrate 2 (IRS2/Irs2) was determined to be a direct target of miR-203a by Luciferase reporter assay. We detected the effects of miR-203a overexpression or inhibition on proliferation and apoptosis of IRS2-overexpressing or IRS2-knockdown MIN6 cells respectively, and preliminarily explored the downstream targets of the IRS2 pathway. NOD mice model was used to detect miR-203a inhibitor treatment for diabetes. Our experiment showed miR-203a was upregulated in pancreatic β cells of hyperglycaemic NOD mice. Elevated miR-203a expression inhibited the proliferation and promoted the apoptosis of MIN6 cells. IRS2/Irs2 is a novel target gene directly regulated by miR-203a and miR-203a overexpression downregulated the expression of IRS2. Irs2 silencing reduced cell proliferation and increased apoptosis. Irs2 overexpression could abolish the pro-apoptotic and anti-proliferative effects of miR-203a on MIN6 cells. Hyperglycemia in newly hyperglycemic NOD mice was under control after treatment with miR-203a inhibitor. Our study suggests that miR-203a regulates pancreatic β cell proliferation and apoptosis by targeting IRS2, treatment with miR-203a inhibitors and IRS2 might provide a new therapeutic strategy for T1DM.

1型糖尿病（T1DM）的主要发病机制是自身免疫介导的胰岛β细胞凋亡。我们试图表征microRNA-203a（miR-203a）对胰岛β细胞增殖和凋亡的功能。原位杂交用于检测miR-203a在正常和高血糖非肥胖糖尿病（NOD）小鼠的胰岛β细胞中的表达。通过细胞计数试剂盒8测量细胞增殖，并使用流式细胞术检测细胞凋亡。通过萤光素酶报告基因测定，胰岛素受体底物2（IRS2 / Irs2）被确定为miR-203a的直接靶标。我们分别检测到miR-203a过表达或抑制对IRS2过表达或IRS2抑制的MIN6细胞增殖和凋亡的影响，并初步探索了IRS2途径的下游靶标。使用NOD小鼠模型检测miR-203a抑制剂对糖尿病的治疗。我们的实验表明，miR-203a在高血糖NOD小鼠的胰腺β细胞中表达上调。升高的miR-203a表达抑制MIN6细胞的增殖并促进其凋亡。IRS2 / Irs2是由miR-203a直接调控的新型靶基因，miR-203a的过表达下调了IRS2的表达。Irs2沉默减少细胞增殖和增加凋亡。Irs2过表达可以消除miR-203a对MIN6细胞的促凋亡和抗增殖作用。使用miR-203a抑制剂治疗后，新的高血糖NOD小鼠的高血糖得到了控制。我们的研究表明，miR-203a通过靶向IRS2来调节胰腺β细胞的增殖和凋亡，