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

• Published in: Toxicology and applied pharmacology Vol. 244; no. 1; pp. 77 - 83
• Main Authors: Pi, Jingbo, Zhang, Qiang, Fu, Jingqi, Woods, Courtney G., Hou, Yongyong, Corkey, Barbara E., Collins, Sheila, Andersen, Melvin E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2010
• Subjects: 60 APPLIED LIFE SCIENCES; ALDEHYDES; Animals; Antioxidant; ANTIOXIDANTS; Antioxidants - metabolism; Antioxidants - therapeutic use; APOPTOSIS; BODY; CARBOHYDRATES; CHEMICAL REACTIONS; DAMAGE; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; DIGESTIVE SYSTEM; DRUGS; ENDOCRINE GLANDS; ENZYMES; GLANDS; GLUCOSE; Glucose - metabolism; GLUTATHIONE; HEXOSES; HORMONES; Humans; HYDROGEN COMPOUNDS; HYDROGEN PEROXIDE; Hypoglycemic Agents - pharmacology; INSULIN; Insulin - metabolism; Insulin secretion; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - enzymology; Insulin-Secreting Cells - metabolism; Ion Channels - metabolism; METABOLISM; Mitochondrial Proteins - metabolism; MONOSACCHARIDES; NF-E2-Related Factor 2 - metabolism; Nrf2; ORGANIC COMPOUNDS; ORGANS; OXIDATION; Oxidative Stress; OXIDOREDUCTASES; OXYGEN COMPOUNDS; PANCREAS; Pancreatic beta-cells; PEPTIDE HORMONES; PEPTIDES; PEROXIDES; POLYPEPTIDES; PROTEINS; RADIOPROTECTIVE SUBSTANCES; Reactive Oxygen Species - metabolism; RESPONSE MODIFYING FACTORS; ROS; SACCHARIDES; Signal Transduction - drug effects; STRESSES; SUPEROXIDE DISMUTASE; Ucp2; Uncoupling Protein 2; O 2; GSSG; NQO1; Oxidative stress; Pancreatic beta-cells; SOD; HO-1; GR; GS; Antioxidant; GPx; Insulin secretion; GCLC; Nrf2; RNS; CAT; GSIS; Prx; ROS; Ucp2; Trx; GSH
• ISSN: 0041-008X; 1096-0333; 1096-0333
• DOI: 10.1016/j.taap.2009.05.025

This review focuses on the emerging evidence that reactive oxygen species (ROS) derived from glucose metabolism, such as H 2O 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.