US EPA

1346268 

Journal Article 

Abstract 

Low-level inorganic arsenite impairs glucose-stimulated insulin secretion in pancreatic beta-cells: involvement of Nrf2-mediated antioxidant response 

Fu, J; Woods, CG; Shnaidman, E; Zhang, Q; Andersen, ME; Collins, S; Pi, J 

2008 

Yes 

Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 

45 

Suppl. 

S156-S157 

English 

WOS:000260867900442 

http://www.sciencedirect.com/science/article/pii/S0891584908006333
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is part of a larger document 3452652 SFRBM's 15th Annual Meeting: Program and Abstracts

There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). a key driver in the pathogenesis of T2D is the impairment of pancreatic beta-cell function, the hallmark of which is decreased glucose-stimulated insulin secretion (GSIS). in contrast to what has been a prevailing beneficial view of antioxidants in preventing beta-cell dysfunction in diabetes, this study proposes that in response to arsenic exposure, transcription factor Nrf2-mediated adaptive induction of endogenous antioxidant enzymes plays a pathophysiological role in beta-cell function. Exposure of INS- 1(832/13) cells or isolated mouse islets to low-levels of arsenite (up to 1 µM for 96 hr; non-cytotoxic) led to decreased GSIS in a dose- and time-dependent fashion. the impaired GSIS was associated with increases in a battery of endogenous antioxidant enzymes, including the transcription factor Nrf2-mediated antioxidant response genes. in addition, intracellular glutathione and total antioxidant potential was significantly increased in the arsenite-treated cells. Accordingly, the increased antioxidant activity noticeably inhibited net glucose-stimulated intracellular H2O2 accumulation, which is involved in GSIS. in contrast to the dramatic induction of antioxidant enzymes, the effects of arsenite exposure on other genes that are associated with glucose transport and metabolism, classical GSIS pathway, insulin synthesis, mitochondrial function, and inflammatory response were also evaluated in the beta-cell models. Taken together our studies suggest that low-level of arsenite exposure causes oxidative stress response, impairs ROS signaling that is involved in GSIS, and thus disturbs beta-cell function. 

Society for Free Radical Biology and Medicine 15th Annual Meeting 

Indianapolis, IN 

November 19-23, 2008