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


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

  • 19501608

Electronic International Standard Serial Number (EISSN)

  • 1096-0333

Digital Object Identifier (DOI)

  • 10.1016/j.taap.2009.05.025


  • eng

Conference Location

  • United States