AMPKγ3 Controls Muscle Glucose Uptake in Recovery From Exercise to Recapture Energy Stores
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Exercise increases muscle glucose uptake independently of insulin signaling and represents a cornerstone for the prevention ofmetabolic disorders. Pharmacological activation of the exercise-responsive AMPK in skeletal muscle has been proven successful as a therapeutic approach to treat metabolic disorders by improving glucose homeostasis through the regulation of muscle glucose uptake. However, conflicting observations cloud the proposed role of AMPK as a necessary regulator of muscle glucose uptake during exercise.We show that glucose uptake increases in human skeletal muscle in the absence of AMPK activation during exercise and that exercise-stimulated AMPKγ3 activity strongly correlates to muscle glucose uptake in the postexercise period. In AMPKγ3-deficient mice, muscle glucose uptake is normally regulated during exercise and contractions but impaired in the recovery period from these stimuli. Impaired glucose uptake in recovery fromexercise and contractions is associated with a lower glucose extraction, which can be explained by a diminished permeability to glucose and abundance of GLUT4 at the muscle plasmamembrane. As a result, AMPKγ3deficiency impairs muscle glycogen resynthesis following exercise. These results identify a physiological function of the AMPKγ3 complex in human and rodent skeletal muscle that regulates glucose uptake in recovery from exercise to recapture muscle energy stores.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Diabetes |
| Vol/bind | 72 |
| Udgave nummer | 10 |
| Sider (fra-til) | 1397-1408 |
| Antal sider | 12 |
| ISSN | 0012-1797 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
The authors thank all the study participants. The authors acknowledge the skilled technical help provided by Betina Bolmgren and Irene Beck Nielsen (Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen) as well as clinical insight provided by Prof. Erik A. Richter (Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen). The authors also acknowledge the Core Facility for Integrated Microscopy, Faculty of Health and Medical Sciences, University of Copenhagen. Figures 1A, 2A, 3A, 4A, and 4D were made using BioRender (https://www.biorender.com/). Funding. Funding for the study was provided by a Danish Diabetes and Endocrine Academy, which is funded by Novo Nordisk Foundation, research grant NNF17SA0031406 (to R.K.). Additional funding for the study was provided from the Independent Research Fund Denmark grant (8020-00288B) (to J.F.P.W.), Novo Nordisk Foundation grant NNF21OC0070370 (to J.F.P.W.), Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research 19K20007 (to K.K.), and the European Foundation for the Study of Diabetes JDS Fellowship Program (to K.K.). None of the funding agencies had any role in the study design or in the collection and interpretation of the data. Duality of Interest. J.F.P.W. has ongoing collaborations with Novo Nordisk unrelated to this work. No other potential conflicts of interest relevant to this article were reported.
Funding Information:
Acknowledgments. The authors thank all the study participants. The authors acknowledge the skilled technical help provided by Betina Bolmgren and Irene Beck Nielsen (Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen) as well as clinical insight provided by Prof. Erik A. Richter (Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen). The authors also acknowledge the Core Facility for Integrated Microscopy, Faculty of Health and Medical Sciences, University of Copenhagen. Figures 1A, 2A,3A,4A,and 4D were made using BioRender (https://www.biorender.com/). Funding. Funding for the study was provided by a Danish Diabetes and Endocrine Academy, which is funded by Novo Nordisk Foundation, research grant NNF17SA0031406 (to R.K.). Additional funding for the study was provided from the Independent Research Fund Denmark grant (8020-00288B) (to J.F.P.W.), Novo Nordisk Foundation grant NNF21OC0070370 (to J.F.P.W.), Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research 19K20007 (to K.K.), and the European Foundation for the Study of Diabetes JDS Fellowship Program (to K.K.).
Publisher Copyright:
© 2023 by the American Diabetes Association.
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