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

Department of Medicine, Endocrinology, and Metabolism, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Cell metabolism (Impact Factor: 16.75). 11/2008; 8(4):325-32. DOI: 10.1016/j.cmet.2008.08.009
Source: PubMed

ABSTRACT 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.

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Available from: Yoshio Fujitani, Aug 22, 2015
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    • "n = 4, ⁄ P < 0.05 vs. control (À). serves as a negative feedback mechanism to clear toxic ubiquitinated protein aggregates in b-cells in diabetic settings including oxidative stress [13] [14]. Therefore, it is presumable that suppression of ROS formation or oxidative stress should inhibit autophagy activation. "
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    • "Nevertheless, a reduction in peptide release is more often associated with a lack of autophagy. For example, glucose-stimulated insulin release in isolated islets is reduced in mice lacking Atg7 specifically in pancreatic beta cells (Ebato et al., 2008). "
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