MiR-149-5p protects against high glucose-induced pancreatic beta cell apoptosis via targeting the BH3-only protein BIM

Abstract

Diabetes mellitus (DM) is characterized by the elevated blood glucose levels and is regarded as one of the most threatening diseases worldwide. The dysfunction of pancreatic beta cells is a key contributor for the pathophysiology of DM. There is growing evidence showing the role of microRNAs (miRNAs) in the regulation of pancreatic beta cell functions. In the present study, we determined the expression of miR-149-5p in pancreatic beta cells under high-glucose (HG) stimulation and explored the underlying mechanism of miR-149-5p-mediated functions of pancreatic beta cells. The results showed the down-regulation of miR-149-5p in the pancreatic beta cell line (MIN6 cells) under HG stimulation. Overexpression of miR-149-5p protected against HG-induced cell apoptosis and impairment of insulin secretion, and attenuated HG-induced an increase in reactive oxygen species (ROS) production in MIN6 cells; while inhibition of miR-149-5p suppressed cell viability, induced cell apoptosis, inhibited insulin secretion and enhanced ROS production in MIN6 cells. Further mechanistic studies revealed that miR-149-5p targeted the BH3-only protein BIM 3′ untranslated region and suppressed BIM expression in MIN6 cells. The rescue experimental assays showed that enforced expression of BIM attenuated the miR-149-5p-mediated effects in HG-stimulated pancreatic beta cells. In conclusion, the present study for the first time elucidated the biological functions of miR-149-5p in regulating pancreatic beta cell functions. The data from the present study provided evidence showing that miR-149-5p protected against HG-induced pancreatic beta cell apoptosis partly via suppressing BIM expression. The therapeutic potential of miR-149-5p in the treatment of DM still requires further detailed investigations.