Mechanisms of β-cell death in type 2 diabetes
Mechanisms of β-cell death in type 2 diabetes
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DOI：
10.2337/diabetes.54.suppl_2.s108
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发表时间：
2005-12-01
期刊：
影响因子：
7.7
通讯作者：
Reinecke, M
中科院分区：
文献类型：
--
作者：
Donath, MY;Ehses, JA;Reinecke, M
产生胰岛素的功能性β细胞数量的减少是2型糖尿病的病理生理机制之一。关于β细胞质量减少与分泌机制固有缺陷的相对贡献，意见不一。在这里，我们回顾了葡萄糖、血脂异常、细胞因子、瘦素、自身免疫和一些磺脲类药物可能导致β细胞适应不良的证据。关于这些致病因素，我们重点介绍了Fas、ATP敏感的K+通道、胰岛素受体底物2、氧化应激、核因子-kappaB、内质网应激和线粒体功能障碍作为它们各自的作用机制。有趣的是，这些因子中的大多数除了在调节β细胞分泌功能和细胞周转方面发挥作用外，还参与炎症过程。因此，调控β细胞增殖、凋亡和功能的机制是密不可分的过程。
A decrease in the number of functional insulin-producing beta-cells contributes to the pathophysiology of type 2 diabetes. Opinions diverge regarding the relative contribution of a decrease in beta-cell mass versus an intrinsic defect in the secretory machinery. Here we review the evidence that glucose, dyslipidemia, cytokines, leptin, autoimmunity, and some sulfonylureas may contribute to the maladaptation of beta-cells. With respect to these causal factors, we focus on Fas, the ATP-sensitive K+ channel, insulin receptor substrate 2, oxidative stress, nuclear factor-kappa B, endoplasmic reticulum stress, and mitochondrial dysfunction as their respective mechanisms of action. Interestingly, most of these factors are involved in inflammatory processes in addition to playing a role in both the regulation of beta-cell secretory function and cell turnover. Thus, the mechanisms regulating beta-cell proliferation, apoptosis, and function are inseparable processes.