To elucidate the potential function of microRNA-96 in protecting pancreatic β cell function under the pathological condition of T2DM and the underlying mechanism. Relative levels of microRNA-96 and genes associated with β cell function in the in vivo and in vitro T2DM and obesity models were detected by qRT-PCR. Insulin functions, including fasting blood glucose, plasma insulin, HOMA-IR, HOMA-%b, glucose tolerance and insulin tolerance, were assessed in microRNA-96 KO mice and wild-type mice fed with normal diet or high-fat diet. Downstream targets of microRNA-96 were verified by dual-luciferase reporter gene assay. Finally, regulatory effects of microRNA-96 on proliferation and apoptosis of MIN6 cells were determined. MicroRNA-96 was upregulated in mice fed with high-fat diet, db/db mice, high-level glucose-treated cells, TNF-α-treated cells, pancreatic cells isolated from the obesity and T2DM patients. Increased fasting blood glucose and HOMA-IR, as well as decreased plasma insulin and HOMA-%b were observed in microRNA-96 KO mice. IPGTT and IPITT results indicated that knockout of microRNA-96 led to pancreatic β cell dysfunction under the pathological condition of T2DM. Dual-luciferase reporter gene assay confirmed that microRNA-96 could bind Foxo1 and Sox6. MicroRNA-96 negatively regulated Foxo1 and Sox6 levels. Moreover, overexpression of microRNA-96 promoted proliferative ability and inhibited apoptosis in MIN6 cells. Relative levels of Pdx1, Nkx6.1, Cyclin D1 and Cyclin E1 were upregulated in MIN6 cells overexpressing microRNA-96. Opposite results were obtained after knockdown of microRNA-96 in MIN6 cells. MicroRNA-96 is upregulated in pancreatic β cells under the pathological condition of T2DM. Overexpression of microRNA-96 promotes proliferative ability and inhibits apoptosis in pancreatic β cells through targeting Foxo1 and Sox6.
Keywords: Foxo1; Sox6; T2DM; microRNA-96.
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