ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell function

Toxicol Appl Pharmacol. 2010 Apr 1;244(1):77-83. doi: 10.1016/j.taap.2009.05.025. Epub 2009 Jun 6.


This review focuses on the emerging evidence that reactive oxygen species (ROS) derived from glucose metabolism, such as H(2)O(2), act as metabolic signaling molecules for glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells. Particular emphasis is placed on the potential inhibitory role of endogenous antioxidants, which rise in response to oxidative stress, in glucose-triggered ROS and GSIS. We propose that cellular adaptive response to oxidative stress challenge, such as nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant induction, plays paradoxical roles in pancreatic beta-cell function. On the one hand, induction of antioxidant enzymes protects beta-cells from oxidative damage and possible cell death, thus minimizing oxidative damage-related impairment of insulin secretion. On the other hand, the induction of antioxidant enzymes by Nrf2 activation blunts glucose-triggered ROS signaling, thus resulting in reduced GSIS. These two premises are potentially relevant to impairment of beta-cells occurring in the late and early stage of Type 2 diabetes, respectively. In addition, we summarized our recent findings that persistent oxidative stress due to absence of uncoupling protein 2 activates cellular adaptive response which is associated with impaired pancreatic beta-cell function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Antioxidants / therapeutic use
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism*
  • Glucose / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Insulin / metabolism
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / enzymology
  • Insulin-Secreting Cells / metabolism*
  • Ion Channels / metabolism
  • Mitochondrial Proteins / metabolism
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction* / drug effects
  • Uncoupling Protein 2


  • Antioxidants
  • Hypoglycemic Agents
  • Insulin
  • Ion Channels
  • Mitochondrial Proteins
  • NF-E2-Related Factor 2
  • Reactive Oxygen Species
  • UCP2 protein, human
  • Uncoupling Protein 2
  • Glucose