microRNA-199a-5p mediates high glucose-induced reactive oxygen species production and apoptosis in INS-1 pancreatic β-cells by targeting SIRT1

Eur Rev Med Pharmacol Sci. 2017 Mar;21(5):1091-1098.

Abstract

Objective: Hyperglycemia-induced pancreatic β-cell loss is a pathologic hallmark of type 2 diabetes mellitus (T2DM). This study was conducted to clarify the function of microRNA (miR)-199a-5p in high glucose-elicited β-cell toxicity and associated molecular mechanisms.

Materials and methods: INS-1 rat pancreatic β-cells were cultured under normal (11 mM) or high (30 mM) glucose for 16-72 h and examined for miR-199a-5p expression. Gain and loss-of-function studies were performed to determine the role of miR-199a-5p in high glucose-induced apoptosis and reactive oxygen species (ROS) production. Additionally, the involvement of SIRT1 in the action of miR-199a-5p was checked.

Results: High glucose caused a significant upregulation of miR-199a-5p in INS-1 cells compared to cells under normal glucose conditions. Pre-transfection with anti-miR-199a-5p inhibitors prevented the reduction in cell viability and inhibited ROS generation in INS-1 cells after high glucose treatment. In contrast, overexpression of miR-199a-5p significantly reduced cell viability and promoted apoptosis and ROS formation in INS-1 cells, which was coupled with a downregulation of SIRT1. Knockdown of SIRT1 led to apoptotic death in INS-1 cells. Moreover, enforced expression of SIRT1 blocked miR-199a-5p-induced ROS generation and attenuated high glucose-mediated apoptosis in INS-1 cells.

Conclusions: miR-199a-5p is upregulated in pancreatic β-cells in response to high glucose and promotes apoptosis and ROS generation by targeting SIRT1. The miR-199a-5p/SIRT1 axis may represent a promising target for the treatment of T2DM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Diabetes Mellitus, Type 2*
  • Glucose
  • MicroRNAs / genetics*
  • Rats
  • Reactive Oxygen Species*
  • Sirtuin 1

Substances

  • MicroRNAs
  • Reactive Oxygen Species
  • mirn199 microRNA, human
  • Sirt1 protein, rat
  • Sirtuin 1
  • Glucose