Chronic reactive oxygen species exposure inhibits glucose uptake and causes insulin resistance in C2C12 myotubes

Biochem Biophys Res Commun. 2016 Sep 16;478(2):798-803. doi: 10.1016/j.bbrc.2016.08.028. Epub 2016 Aug 5.

Abstract

Reactive oxygen species (ROS) is an important regulator in cellular signaling transduction, and many previous studies have indicated that acute ROS stimulation improves insulin sensitivity in skeletal muscle. In the study, we found that chronic ROS treatment caused serious insulin resistance in C2C12 myotubes. Glucose uptake and consumption assay indicated that pretreatment with 80 μM H2O2 for 2 h inhibited insulin-stimulated glucose uptake in C2C12 myotubes, and the reason for it, is that chronic H2O2 treatment decreased insulin-induced glucose transporter 4 (GLUT4) translocation from cell plasma to cell membrane. Moreover, Akt2 phosphorylation depended on insulin was reduced in C2C12 myotubes of chronic H2O2 treatment. Together, this study provides further demonstration that chronic ROS stress is associated with insulin resistance of skeletal muscle in the progression of type 2 diabetes.

Keywords: Akt2; C2C12 myotubes; GLUT4; Glucose uptake; Insulin resistance; Reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Gene Expression
  • Glucose / antagonists & inhibitors*
  • Glucose / metabolism
  • Glucose Transporter Type 4 / genetics
  • Glucose Transporter Type 4 / metabolism
  • Hydrogen Peroxide / pharmacology*
  • Insulin / metabolism*
  • Insulin / pharmacology
  • Insulin Resistance*
  • Mice
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / drug effects*
  • Muscle Fibers, Skeletal / metabolism
  • Myoblasts / cytology
  • Myoblasts / drug effects
  • Myoblasts / metabolism
  • Phosphorylation / drug effects
  • Protein Transport
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • Glucose Transporter Type 4
  • Insulin
  • Slc2a4 protein, mouse
  • Hydrogen Peroxide
  • Akt2 protein, mouse
  • Proto-Oncogene Proteins c-akt
  • Glucose