详细记录  
题名:Divergent Effects of Sulforaphane on Basal and Glucose-Stimulated Insulin Secretion in beta-Cells: Role of Reactive Oxygen Species and Induction of Endogenous Antioxidants.
作者:FU J; ZHANG Q; WOODS CG; ZHENG H; YANG B; QU W; ANDERSEN ME; PI J;
来源:Pharm Res. 2013 Mar 7. [ IF= 0.00 ] ]
URL :10.1007/s11095-013-1013-8
日期:20130330
摘要:PURPOSE: Oxidative stress is implicated in pancreatic beta-cell dysfunction, yet
clinical outcomes of antioxidant therapies on diabetes are inconclusive. Since
reactive oxygen species (ROS) can function as signaling intermediates for
glucose-stimulated insulin secretion (GSIS), we hypothesize that exogenously
boosting cellular antioxidant capacity dampens signaling ROS and GSIS. METHODS:
To test the hypothesis, we formulated a mathematical model of redox homeostatic
control circuit comprising known feedback and feedforward loops and validated
model predictions with plant-derived antioxidant sulforaphane (SFN). RESULTS: SFN
acutely (30-min treatment) stimulated basal insulin secretion in INS-1(832/13)
cells and cultured mouse islets, which could be attributed to SFN-elicited ROS as
N-acetylcysteine or glutathione ethyl ester suppressed SFN-stimulated insulin
secretion. The mathematical model predicted an adapted redox state characteristic
of strong induction of endogenous antioxidants but marginally increased ROS under
prolonged SFN exposure, a state that attenuates rather than facilitates
glucose-stimulated ROS and GSIS. We validated the prediction by demonstrating
that although 24-h treatment of INS-1(832/13) cells with low, non-cytotoxic
concentrations of SFN (2-10 muM) protected the cells from cytotoxicity by
oxidative insult, it markedly suppressed insulin secretion stimulated by 20 mM
glucose. CONCLUSIONS: Our study indicates that adaptive induction of endogenous
antioxidants by exogenous antioxidants, albeit cytoprotective, inhibits GSIS in
beta-cells.

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