Reactive oxygen species as a signal in glucose-stimulated insulin secretion
Reactive oxygen species as a signal in glucose-stimulated insulin secretion
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DOI：
10.2337/db06-1601
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发表时间：
2007-07-01
期刊：
影响因子：
7.7
通讯作者：
Collins, Sheila
中科院分区：
文献类型：
--
作者：
Pi, Jingbo;Bai, Yushi;Collins, Sheila
P细胞的独特特征之一是它们相对低表达许多抗氧化酶。这可能使P细胞对氧化损伤敏感，但也可能提供对活性氧作为信号敏感的系统。在分离的小鼠胰岛和INS-1（832/13）细胞中，葡萄糖增加H2 O2的细胞内积累。在这两种模型中，胰岛素分泌可以通过提供外源性H2 O2或马来酸二乙酯来刺激，从而提高细胞内H2 O2水平。提供外源性H2 O2清除剂（包括细胞可渗透的过氧化氢酶和N-乙酰基-L-半胱氨酸）可以抑制葡萄糖刺激的H2 O2积累和胰岛素分泌（GSIS）。与此相反，细胞渗透性超氧化物歧化酶，代谢超氧化物为H2 O2，GSIS没有影响。由于氧化应激是糖尿病中β细胞功能障碍的重要危险因素，因此在各种氧化应激条件下研究了葡萄糖诱导的H-2、O-2生成与GSIS之间的关系。急性暴露的小鼠胰岛或INS-1（832/ 13）细胞的氧化应激，包括亚砷酸盐，4-羟基壬烯醛，和甲基乙二醛，导致GSIS降低。这种受损的GSIS与内源性抗氧化酶的增加有关。总而言之，这些发现表明，来自葡萄糖代谢的H2 O2是胰岛素分泌的代谢信号之一，而氧化应激可能会扰乱其信号功能。
One of the unique features of P-cells is their relatively low expression of many antioxidant enzymes. This could render P-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 H-2,O-2, 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.