Mitochondria mediated cell death in diabetes
Mitochondria mediated cell death in diabetes
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DOI：
10.1007/s10495-009-0363-5
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发表时间：
2009-05
期刊：
影响因子：
7.2
通讯作者：
G. Szabadkai;M. Duchen
中科院分区：
文献类型：
--
作者：
G. Szabadkai;M. Duchen
线粒体功能障碍在包括神经退行性疾病、癌症和糖尿病在内的一系列疾病的发病机制中起着重要作用，这些疾病涉及细胞燃料代谢紊乱和生存/死亡途径。细胞因子、病毒识别和细胞应激途径聚集在线粒体上导致1型糖尿病β细胞凋亡和/或坏死细胞死亡。此外，由于线粒体为葡萄糖刺激胰岛素分泌（GSIS）产生关键的代谢信号，线粒体功能障碍是GSIS功能紊乱和（过度营养）应激诱导的凋亡/坏死β细胞死亡的基础，这是2型糖尿病的标志。在糖尿病的发展过程中，控制β细胞生死决定的明显不同的机制提供了一个显著的例子，即远程代谢、免疫和应激信号与线粒体介导的凋亡/坏死死亡途径相遇，从而决定β细胞的命运。我们总结了在当前糖尿病研究趋势的背景下，支持线粒体在β细胞死亡中的关键作用的主要发现。
Mitochondrial dysfunction plays a role in the pathogenesis of a wide range of diseases that involve disordered cellular fuel metabolism and survival/death pathways, including neurodegenerative diseases, cancer and diabetes. Cytokine, virus recognition and cellular stress pathways converging on mitochondria cause apoptotic and/or necrotic cell death of β-cells intype-1diabetes. Moreover, since mitochondria generate crucial metabolic signals for glucose stimulated insulin secretion (GSIS), mitochondrial dysfunction underlies both the functional derangement of GSIS and (over-nutrition) stress-induced apoptotic/necrotic β-cell death, hallmarks oftype-2diabetes. The apparently distinct mechanisms governing β-cell life/death decisions during the development of diabetes provide a remarkable example where remotemetabolic, immune and stress signallingmeet with mitochondria mediated apoptotic/necrotic death pathwaysto determine the fate of the β-cell. We summarize the main findings supporting such a pivotal role of mitochondria in β-cell death in the context of current trends in diabetes research.