Reactive oxygen species as a signal in glucose-stimulated insulin secretion.
One of the unique features of beta-cells is their relatively low expression of many antioxidant enzymes. This could render beta-cells susceptible to oxidative damage but may also provide a system that is sensitive to reactive oxygen species as signals. In isolated mouse islets and INS-1(832/13) cells, glucose increases intracellular accumulation of H2O2. In both models, insulin secretion could be stimulated by provision of either exogenous H2O2 or diethyl maleate, which raises intracellular H2O2 levels. Provision of exogenous H2O2 scavengers, including cell permeable catalase and N-acetyl-L-cysteine, inhibited glucose-stimulated H2O2 accumulation and insulin secretion (GSIS). In contrast, cell permeable superoxide dismutase, which metabolizes superoxide into H2O2, had no effect on GSIS. Because oxidative stress is an important risk factor for beta-cell dysfunction in diabetes, the relationship between glucose-induced H2O2 generation and GSIS was investigated under various oxidative stress conditions. Acute exposure of isolated mouse islets or INS-1(832/13) cells to oxidative stressors, including arsenite, 4-hydroxynonenal, and methylglyoxal, led to decreased GSIS. This impaired GSIS was associated with increases in a battery of endogenous antioxidant enzymes. Taken together, these findings suggest that H2O2 derived from glucose metabolism is one of the metabolic signals for insulin secretion, whereas oxidative stress may disturb its signaling function.
Pi
Jingbo
J
Endocrine Biology Program, The Hamner Institutes for Health Sciences, 6 Davis Dr., Research Triangle Park, NC 27709, USA. jpi@thehamner.org
Bai
Yushi
Y
Zhang
Qiang
Q
Wong
Victoria
V
Floering
Lisa M
LM
Daniel
Kiefer
K
Reece
Jeffrey M
JM
Deeney
Jude T
JT
Andersen
Melvin E
ME
Corkey
Barbara E
BE
Collins
Sheila
S
D000222:Adaptation, Physiological; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002478:Cells, Cultured; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D023421:Models, Animal; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
D001786:Blood Glucose; D007328:Insulin; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide