Autophagy Is Important in Islet Homeostasis and Compensatory Increase of Beta Cell Mass in Response to High-Fat Diet
Autophagy Is Important in Islet Homeostasis and Compensatory Increase of Beta Cell Mass in Response to High-Fat Diet
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DOI：
10.1016/j.cmet.2008.08.009
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发表时间：
2008-10-08
期刊：
影响因子：
29
通讯作者：
Watada, Hirotaka
中科院分区：
文献类型：
--
作者：
Ebato, Chie;Uchida, Toyoyoshi;Watada, Hirotaka
自噬是一种进化上保守的细胞质组分大量降解的机制。在这里，我们报告了糖尿病db/db和非糖尿病高脂喂养的C57 BL/6小鼠胰腺β细胞中自噬体形成的上调。游离脂肪酸（FFA）可引起与糖尿病相关的外周胰岛素抵抗，诱导β细胞自噬。β细胞中atg 7的基因切除导致胰岛变性和葡萄糖耐量受损，胰岛素分泌减少。虽然高脂饮食刺激对照小鼠的β细胞自噬，但它诱导自噬缺陷突变体的葡萄糖耐量严重恶化，部分原因是β细胞质量缺乏代偿性增加。这些发现表明，基础自噬对于维持正常胰岛结构和功能是重要的。结果还确定了诱导性自噬作为β细胞在高脂饮食诱导的胰岛素抵抗存在下的适应性反应的独特作用。
Autophagy is an evolutionarily conserved machinery for bulk degradation of cytoplasmic components. Here, we report upregulation of autophagosome formation in pancreatic beta cells in diabetic db/db and in nondiabetic high-fat-fed C57BL/6 mice. Free fatty acids (FFAs), which can cause peripheral insulin resistance associated with diabetes, induced autophagy in beta cells. Genetic ablation of atg7 in beta cells resulted in degeneration of islets and impaired glucose tolerance with reduced insulin secretion. While high-fat diet stimulated beta cell autophagy in control mice, it induced profound deterioration of glucose tolerance in autophagy-deficient mutants, partly because of the lack of compensatory increase in beta cell mass. These findings suggest that basal autophagy is important for maintenance of normal islet architecture and function. The results also identified a unique role for inductive autophagy as an adaptive response of beta cells in the presence of insulin resistance induced by high-fat diet.