Hv1-deficiency protects β cells from glucotoxicity through regulation of NOX4 level

Biochem Biophys Res Commun. 2019 May 28;513(2):434-438. doi: 10.1016/j.bbrc.2019.03.195. Epub 2019 Apr 6.

Abstract

High glucose (HG)-induced oxidative stress contributes to the dysfunction of pancreatic β cells in diabetes. The voltage-gated proton channel Hv1 has been proposed to support reactive oxygen species (ROS) production during respiratory bursts. However, the effect of Hv1 on glucotoxicity in pancreatic β cells is not clear yet. In this study, we examined the protective effects of Hv1-deficiency in HG cultured β cells. Following 48 h of treatment with 30 mM high glucose, Hv1 KO β cells showed higher cell viability, lower cell apoptosis and a more stable insulin gene expression level compared to WT β cells. In both control and HG cultured β cells, deficiency of Hv1 decreased the glucose- and PMA-induced ROS production. Finally, HG incubation led to NOX4 upregulation in WT β cells, which could be inhibited by HV1 deficiency. In conclusion, Hv1-deficiency prevents the HG treatment-induced NOX4 upregulation and protects β cells from glucotoxicity.

Keywords: Glucotoxicity; NOX4; Pancreatic β cells; ROS; Voltage-gated proton channel Hv1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cells, Cultured
  • Gene Knockout Techniques
  • Glucose / metabolism
  • Hyperglycemia / genetics
  • Hyperglycemia / metabolism*
  • Hyperglycemia / pathology
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Mice, Inbred C57BL
  • NADPH Oxidase 4 / genetics
  • NADPH Oxidase 4 / metabolism*
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism
  • Up-Regulation

Substances

  • Hv1 proton channel, mouse
  • Ion Channels
  • Reactive Oxygen Species
  • NADPH Oxidase 4
  • Nox4 protein, mouse
  • Glucose