Autophagy Is Important in Islet Homeostasis and Compensatory Increase of Beta Cell Mass in Response to High-Fat Diet

作者：Ebato Chie; Uchida Toyoyoshi; Arakawa Masayuki; Komatsu Masaaki; Ueno Takashi; Komiya Koji; Azuma Kosuke; Hirose Takahisa; Tanaka Keiji; Kominami Eiki; Kawamori Ryuzo; Fujitani Yoshio^*; Watada Hirotaka

来源：Cell Metabolism, 2008, 8(4): 325-332.

DOI：10.1016/j.cmet.2008.08.009

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.

• 出版日期2008-10-8
• 单位河北医科大学