Overexpression of microRNA-26a protects against deficient β-cell function via targeting phosphatase with tensin homology in mouse models of type 2 diabetes

The prevalence of type 2 diabetes mellitus (T2DM) increased rapidly in the world. The development of beta-cell dysfunction is the quintessential defects in T2DM patients However, the pathogenesis of beta-cell dysfunction is still unclear. MicroRNAs are short non-coding RNAs and has been reported to be involved in pathogenesis of beta-cell dysfunction and T2DM. Here, we investigated the mechanisms by which miR26a regulate beta-cell function and insulin signaling pathway in high fat diet (HFD) fed and db/db T2DM mice model. The expression of miR-26a was down-regulated dramatically in the serum and islets of both HFD and db/db mice model. miR-26a overexpression protected against HFD-induced diabetes and maintained prolonged normoglycemic time in HFD fed mice. Overexpression of miR-26a improved beta-cell dysfunction in T2DM mice. Further, we identified that PTEN is a direct target gene of miR-26a. Over expression of miR-26a significantly inhibited the luciferase activity of hPTEN 3'-UTR, while the effect of miR-26a disappeared when the miR-26a potential binding site within the PTEN 3'-UTR was mutated. Overexpression of miR-26a reduced both the mRNA and protein levels of PTEN in vitro and in vivo. We also found that miR-26a overexpression increased the expression of p-Akt and p-FoxO-1, while the effect of miR-26a was blocked by PTEN overexpression. In conclusion, our data indicated that miR-26a potentially contributes to the beta-cell dysfunction in T2DM, and miR-26a may be a new therapeutic strategy against T2DM. (C) 2017 Elsevier Inc. All rights reserved.