β-cell apoptosis and defense mechanisms -: Lessons from type 1 diabetes
β-cell apoptosis and defense mechanisms -: Lessons from type 1 diabetes
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DOI：
10.2337/diabetes.50.2007.s64
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发表时间：
2001-02-01
期刊：
影响因子：
7.7
通讯作者：
Darville, MI
中科院分区：
文献类型：
--
作者：
Eizirik, DL;Darville, MI
越来越多的证据表明，细胞凋亡是早期1型糖尿病β细胞死亡的主要方式。细胞因子介导β细胞凋亡，在这篇文章中，我们讨论了一些可能有助于β细胞存活或死亡的甘氨酸修饰基因。编码诱导型一氧化氮合酶的基因分别在啮齿动物和人胰岛中被白细胞介素（IL）-1 β或IL-1 β加γ-干扰素诱导。这导致一氧化氮（NO）的形成，其在很大程度上导致β-细胞坏死，在很小程度上导致β-细胞凋亡过程.在人β细胞中由细胞因子诱导的细胞死亡的主要模式是细胞凋亡，而在大鼠和小鼠β细胞中细胞因子导致坏死和细胞凋亡。这表明，在啮齿类动物胰岛的坏死成分是由于NO诱导的线粒体损伤，从而减少ATP的生产。人类胰岛具有更好的抗氧化防御能力，能够保持葡萄糖氧化和ATP产生，因此可以在细胞因子传递的去β ath信号后完成凋亡程序。我们建议，这种死亡信号的结果，从苦参碱诱导的多个促凋亡和促生存基因的表达的平行和/或顺序的变化。这些“基因模块”和调节它们的转录因子的身份仍有待确定。
Increased evidence suggests that apoptosis is the main mode of beta -cell death in early type 1 diabetes. Cytokines mediate beta -cell apoptosis, and in this article, we discuss some of the cytokine-modified genes that may contribute to beta -cell survival or death. The gene encoding for the inducible form of nitric oxide synthase is induced by interleukin (IL)-1 beta or IL-1 beta plus gamma -interferon in rodent and human islets, respectively. This leads to nitric oxide (NO) formation, which contributes to a major extent to beta -cell necrosis and to a minor extent to the process of beta -cell apoptosis. The main mode of cell death induced by cytokines in human beta -cells is apoptosis, whereas cytokines lead to both necrosis and apoptosis in rat and mouse beta -cells. It is suggested that the necrotic component in rodent islets is due to NO-induced mitochondrial impairment and consequent decreased ATP production. Human islets, possessing better antioxidant defenses, are able to preserve glucose oxidation and ATP production, and can thus complete the apoptotic program after the de beta ath signal delivered by cytokines. We propose that this death signal results from cytokine-induced parallel and/or sequential changes in the expression of multiple proapoptotic and prosurvival genes. The identity of these "gene modules" and of the transcription factors regulating them remains to be established.