Role of apoptosis in pancreatic β-cell death in diabetes
Role of apoptosis in pancreatic β-cell death in diabetes
复制标题
DOI：
10.2337/diabetes.50.2007.s44
复制
发表时间：
2001-02-01
期刊：
影响因子：
7.7
通讯作者：
Orrenius, S
中科院分区：
文献类型：
--
作者：
Chandra, J;Zhivotovsky, B;Orrenius, S
细胞凋亡是细胞在正常发育过程中死亡的一种生理形式，这一过程的关键介质包括半胱氨酸天冬氨酸氨基转移酶、活性氧和钙离子。胰腺β细胞的过度凋亡与糖尿病有关。因此，细胞凋亡的研究主要集中在渗透的巨噬细胞或细胞毒性T细胞如何通过细胞因子或死亡受体的触发来杀死胰岛β细胞。与此同时，靶细胞中的细胞内事件在很大程度上被忽略了。阐明这些靶点可能有助于开发改进的糖尿病治疗策略。本文将概述细胞凋亡研究的最新进展，重点介绍可能与1型和2型糖尿病的β细胞死亡相关的机制。在β细胞杀伤中提出的几个模型都集中在Ca~(2+)信号上，表明胰腺β细胞可能是仔细分析Ca~(2+)在细胞凋亡中作用的理想系统。
Apoptosis is a physiological form of cell death that occurs during normal development, and critical mediators of this process include caspases, reactive oxygen species, and Ca2+. Excessive apoptosis of the pancreatic beta -cell has been associated with diabetes. Consequently, apoptosis research has focused on how infiltrating macrophages or cytotoxic T-cells might kill pancreatic beta -cells using cytokines or death receptor triggering. Meanwhile, the intracellular events in the target beta -cell have been largely ignored. Elucidation of such targets might help develop improved treatment strategies for diabetes. This article will outline recent developments in apoptosis research, with emphasis on mechanisms that may be relevant to beta -cell death in type 1 and type 2 diabetes. Several of the models proposed in beta -cell killing converge on Ca2+ signaling, indicating that the pancreatic beta -cell may be an ideal system in which to carefully dissect the role of Ca2+ during apoptosis.