AMPK binds to Sestrins and mediates the effect of exercise to increase insulin-sensitivity through autophagy
- PMID: 25672217
- DOI: 10.1016/j.metabol.2015.01.015
AMPK binds to Sestrins and mediates the effect of exercise to increase insulin-sensitivity through autophagy
Abstract
Objective: Exercise has beneficial effects on human health, including protection against metabolic disorders such as diabetes. However, the cellular mechanisms underlying the metabolic effects of exercise are not completely understood. We know that autophagy plays an important role in maintaining cellular homeostasis. In this study, we aimed to better understand the metabolic effects of autophagy in skeletal muscle and the role of Sestrins/AMPK in mediating the beneficial effects of physical exercise through autophagy.
Material/methods: We used wild type and AMPKα2(-/-) C57BL/6 mice as animal models to elucidate the role of AMPK in autophagy activation and the metabolism-promoting effects of acute and regular exercise. C2C12 myotubes were used to study the metabolic effects of autophagy in vitro.
Results: Autophagy promotes glucose uptake in skeletal muscle. A single bout of exercise increased the activity of autophagy in the skeletal muscle of wild type mice but not of AMPKα2(-/-) mice. This difference was associated with increased amounts of both Sestrin2 and Sestrin3 coimmunoprecipitated with AMPKα2. Long-term physical exercise significantly increased the basal level of muscle autophagy and protein expression of Sestrin2 and Sestrin3 in both normal chow and high-fat diet-fed mice.
Conclusion: We believe that exercise-induced AMPK and Sestrins interaction may be involved in the beneficial metabolic effects of exercise by activating autophagy. This interaction provides a molecular mechanism that is a potential target in metabolic syndromes.
Keywords: AMP-activated protein kinase; Autophagy; Exercise; Metabolism; Sestrins.
Copyright © 2015 Elsevier Inc. All rights reserved.
Comment in
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Exercising insulin sensitivity: AMPK turns on autophagy!Metabolism. 2015 Jun;64(6):655-7. doi: 10.1016/j.metabol.2015.03.002. Epub 2015 Mar 14. Metabolism. 2015. PMID: 25819737 Free PMC article. No abstract available.
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