Apoptosis in the beta cells: cause or consequence of insulin secretion defect in diabetes?
Apoptosis in the beta cells: cause or consequence of insulin secretion defect in diabetes?
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DOI：
10.1080/078538902321012397
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发表时间：
2002-01-01
影响因子：
4.4
通讯作者：
Sesti, G
中科院分区：
文献类型：
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作者：
Sesti, G
胰腺β细胞功能障碍和胰岛素抵抗是2型糖尿病病理生理学中两个相互关联的缺陷。外周胰岛素作用的缺陷先于葡萄糖耐受不良的发展，因为胰腺通过增加胰岛素的产生和分泌来补偿胰岛素抵抗。这可以通过增强细胞分泌能力或通过增加β细胞质量来实现。随着时间的推移，胰岛素的胰腺分泌变得不足以达到胰岛素抵抗的程度，并且空腹和餐后葡萄糖水平升高，导致明显的高血糖症的发作，这通过称为葡萄糖毒性的过程导致β细胞功能和存活率的降低。越来越多的证据表明，细胞凋亡是胰腺β细胞死亡的主要模式，不仅在1型糖尿病中，而且在2型糖尿病中。最近，在基因敲除小鼠、人类和大鼠胰岛以及胰腺β细胞系中的研究表明，β细胞中的胰岛素信号传导缺陷可能通过影响分泌功能和细胞存活而发挥重要的病理生理作用。本综述的目的是介绍最近的进展，在2型糖尿病的胰岛素分泌缺陷和β细胞存活的分子机制之间的相互关系的理解受损的激活胰岛素信号通路。
Pancreatic beta-cell dysfunction and insulin resistance are two interrelated defects in the pathophysiology of type 2 diabetes. Defects in peripheral insulin action precede the development of glucose intolerance, as the pancreas compensates for insulin resistance by increasing insulin production and secretion. This may be achieved by enhancing cellular secretory capacity or by increasing beta-cell mass. Over time, the pancreatic secretion of insulin becomes inadequate for the extent of insulin resistance, and the levels of fasting and postprandial glucose rise leading to the onset of frank hyperglycemia, which leads to reduction in beta-cell function and survival through a process referred to as glucose toxicity. There is increasing evidence that apoptosis is the main mode of pancreatic beta-cell death not only in type 1 but also in type 2 diabetes. Recently, studies in knockout mice, human and rat islets, and pancreatic beta-cell lines demonstrated that defective insulin signaling in beta-cells might play an important pathophysiological role by affecting both secretory function and cell survival. The purpose of this review is to present recent advances in understanding of the interrelationship between molecular mechanisms underlying defects in insulin secretion and beta-cell survival in type 2 diabetes caused by impaired activation of insulin signaling pathways.