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

Journal Article · Thu Apr 01 00:00:00 EDT 2010 · Toxicology and Applied Pharmacology

OSTI ID:21344909

Qiang, Zhang ^[1]; Jingqi, Fu ^[2]; Woods, Courtney G ^[1]; Yongyong, Hou ^[2]; Corkey, Barbara E ^[3]; Collins, Sheila ^[2]; Andersen, Melvin E ^[1]

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1. Division of Computational Biology, Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States)
2. Division of Translational Biology, Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States)
3. Obesity Research Center, Boston University School of Medicine, Boston, MA 02118 (United States)

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

• OSTI ID: 21344909
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 244; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ALDEHYDES
ANTIOXIDANTS
APOPTOSIS
BODY
CARBOHYDRATES
CHEMICAL REACTIONS
DAMAGE
DIGESTIVE SYSTEM
DRUGS
ENDOCRINE GLANDS
ENZYMES
GLANDS
GLUCOSE
GLUTATHIONE
HEXOSES
HORMONES
HYDROGEN COMPOUNDS
HYDROGEN PEROXIDE
INSULIN
METABOLISM
MONOSACCHARIDES
ORGANIC COMPOUNDS
ORGANS
OXIDATION
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PANCREAS
PEPTIDE HORMONES
PEPTIDES
PEROXIDES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RESPONSE MODIFYING FACTORS
SACCHARIDES
STRESSES
SUPEROXIDE DISMUTASE