Chandra J, Zhivotovsky B, Zaitsev S, Juntti-Berggren L, Berggren P O, Orrenius S
Division of Toxicology, Institute for Environmental Medicine, Stockholm, Sweden.
Diabetes. 2001 Feb;50 Suppl 1:S44-7. doi: 10.2337/diabetes.50.2007.s44.
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.
细胞凋亡是一种在正常发育过程中发生的生理性细胞死亡形式，该过程的关键介质包括半胱天冬酶、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，细胞凋亡研究聚焦于浸润性巨噬细胞或细胞毒性T细胞如何利用细胞因子或死亡受体触发来杀死胰腺β细胞。与此同时，目标β细胞内的事件在很大程度上被忽视了。阐明此类靶点可能有助于开发出更好的糖尿病治疗策略。本文将概述细胞凋亡研究的最新进展，重点关注可能与1型和2型糖尿病中β细胞死亡相关的机制。在β细胞杀伤中提出的几种模型都集中在钙离子信号传导上，这表明胰腺β细胞可能是一个理想的系统，可用于仔细剖析钙离子在细胞凋亡过程中的作用。
