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AMPK activation of muscle autophagy prevents fasting-induced hypoglycemia and myopathy during aging
Bujak, Adam L. Crane, Justin D. Lally, James S. Ford, Rebecca J. Kang, Sally J. Rebalka, Irena A. Green, Alex E. Kemp, Bruce Ernest Hawke, Thomas J. Schertzer, Jonathan D.
Bujak, Adam L.
Crane, Justin D.
Lally, James S.
Ford, Rebecca J.
Kang, Sally J.
Rebalka, Irena A.
Green, Alex E.
Kemp, Bruce Ernest
Hawke, Thomas J.
Schertzer, Jonathan D.
Abstract
The AMP-activated protein kinase ( AMPK ) activates autophagy, but its role in aging and fasting-induced muscle function has not been defined. Here we report that fasting mice lacking skeletal muscle AMPK ( AMPK-MKO ) results in hypoglycemia and hyperketosis. This is not due to defective fatty acid oxidation, but instead is related to a block in muscle proteolysis that leads to reduced circulating levels of alanine, an essential amino acid required for gluconeogenesis. Markers of muscle autophagy including phosphorylation of Ulk1 Ser555 and Ser757 and aggregation of RFP-LC3 puncta are impaired. Consistent with impaired autophagy, aged AMPK-MKO mice possess a significant myopathy characterized by reduced muscle function, mitochondrial disease, and accumulation of the autophagy/mitophagy proteins p62 and Parkin. These findings establish an essential requirement for skeletal muscle AMPK-mediated autophagy in preserving blood glucose levels during prolonged fasting as well as maintaining muscle integrity and mitochondrial function during aging.
Keywords
Date
2015
Type
Journal article
Journal
Cell Metabolism
Book
Volume
21
Issue
6
Page Range
883-890
Article Number
ACU Department
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
License
File Access
Controlled