ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell function.
ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell function.
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DOI：
10.1016/j.taap.2009.05.025
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发表时间：
2010-04-01
影响因子：
3.8
通讯作者：
Andersen ME
中科院分区：
文献类型：
--
作者：
Pi J;Zhang Q;Fu J;Woods CG;Hou Y;Corkey BE;Collins S;Andersen ME
本文综述了近年来发现的一些新的证据，即来源于葡萄糖代谢的活性氧(ROS)，如过氧化氢，在胰岛β细胞中作为葡萄糖刺激的胰岛素分泌(GSIS)的代谢信号分子。特别强调了内源性抗氧化剂在葡萄糖触发的ROS和GSIS中的潜在抑制作用，内源性抗氧化剂在氧化应激反应中上升。我们认为，细胞对氧化应激攻击的适应性反应，如核因子E2相关因子2(NRF2)介导的抗氧化诱导，在胰岛β细胞功能中扮演着矛盾的角色。一方面，抗氧化酶的诱导保护β细胞免受氧化损伤和可能的细胞死亡，从而将与氧化损伤相关的胰岛素分泌损害降至最低。另一方面，Nrf2的激活诱导抗氧化酶减弱葡萄糖触发的ROS信号，从而导致GSIS降低。这两个前提可能分别与2型糖尿病晚期和早期的β细胞损伤有关。此外，我们总结了我们最近的发现，由于缺乏解偶联蛋白2而导致的持续氧化应激激活了细胞适应性反应，这与胰岛β细胞功能受损有关。
This review focuses on the emerging evidence that reactive oxygen species (ROS) derived from glucose metabolism, such as H2O2, 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.
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