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

Journal Article (Journal Article;Review)

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.

Full Text

Duke Authors

Cited Authors

  • Pi, J; Zhang, Q; Fu, J; Woods, CG; Hou, Y; Corkey, BE; Collins, S; Andersen, ME

Published Date

  • April 1, 2010

Published In

Volume / Issue

  • 244 / 1

Start / End Page

  • 77 - 83

PubMed ID

  • 19501608

Pubmed Central ID

  • PMC2837798

Electronic International Standard Serial Number (EISSN)

  • 1096-0333

Digital Object Identifier (DOI)

  • 10.1016/j.taap.2009.05.025


  • eng

Conference Location

  • United States