The role of autophagy in β-cell lipotoxicity and type 2 diabetes.
The role of autophagy in β-cell lipotoxicity and type 2 diabetes.
复制标题
DOI：
10.1111/j.1463-1326.2010.01268.x
复制
发表时间：
2010-10
期刊：
影响因子：
--
通讯作者：
Shirihai OS
中科院分区：
文献类型：
--
作者：
Las G;Shirihai OS
自噬是一种普遍存在的参与细胞存活和死亡的分解代谢途径，与许多年龄相关疾病有关。最近的研究结果表明，自噬对于适当的胰岛素分泌和β细胞活力至关重要。在其β细胞中缺乏自噬的转基因小鼠表现出β细胞质量减少和葡萄糖刺激的胰岛素分泌抑制。多项研究表明，应激可以刺激β细胞中的自噬：在糖尿病的不同体内模型中，如db/db小鼠、高脂饮食小鼠、pdx-1基因敲除小鼠，以及体外葡萄糖毒性和脂毒性模型中，自噬体的数量增加。自噬的药理学和分子抑制增加了对细胞应激的易感性，表明自噬保护免受糖尿病相关应激。然而，最近的研究结果对这些结论提出了质疑。糖尿病患者的胰腺和暴露于脂肪酸的β细胞显示异常自噬体形态的积累和溶酶体基因表达的抑制，表明自噬转换受损。在这篇综述中，我们试图概述其他人和我们在自噬在糖尿病中可能发挥的作用方面所产生的数据，这种作用取决于条件，在应对压力方面可能是有益的或有害的。
Autophagy, a ubiquitous catabolic pathway involved in both cell survival and cell death, has been implicated in many age-associated diseases. Recent findings have shown autophagy to be crucial for proper insulin secretion and β-cell viability. Transgenic mice lacking autophagy in their β-cells showed decreased β-cell mass and suppressed glucose-stimulated insulin secretion. Several studies showed that stress can stimulate autophagy in β-cells: the number of autophagosomes is increased in different in vivo models for diabetes, such as db/db mice, mice fed high-fat diet, pdx-1 knockout mice, as well as in in vitro models of glucotoxicity and lipotoxicity. Pharmacological and molecular inhibition of autophagy increases the susceptibility to cell stress, suggesting that autophagy protects against diabetes-relevant stresses. Recent findings, however, question these conclusions. Pancreases of diabetics and β-cells exposed to fatty acids show accumulation of abnormal autophagosome morphology and suppression of lysosomal gene expression suggesting impairment in autophagic turnover. In this review we attempt to give an overview of the data generated by others and by us in view of the possible role of autophagy in diabetes, a role which depending on the conditions, could be beneficial or detrimental in coping with stress.
登录
查看更多内容
影响因子：
11.1
作者：
He C;Klionsky DJ
通讯作者：
Klionsky DJ
影响因子：
7.7
作者：
Kaniuk, Natalia A.;Kiraly, Michael;Brumell, John H.
通讯作者：
Brumell, John H.
影响因子：
4.8
作者：
Choi, Sung-E;Lee, Sung-Mi;Kang, Yup
通讯作者：
Kang, Yup
影响因子：
3.9
作者：
Cnop, Miriam;Igoillo-Esteve, Mariana;Eizirik, Decio L.
通讯作者：
Eizirik, Decio L.
影响因子：
8.2
作者：
Masini, M.;Bugliani, M.;Marchetti, P.
通讯作者：
Marchetti, P.