Effect of acute activation of 5′-AMP-activated protein kinase on glycogen regulation in isolated rat skeletal muscle
Abstract
5′-AMP-activated protein kinase (AMPK) has been implicated in glycogen metabolism in skeletal muscle. However, the physiological relevance of increased AMPK activity during exercise has not been fully clarified. This study was performed to determine the direct effects of acute AMPK activation on muscle glycogen regulation. For this purpose, we used an isolated rat muscle preparation and pharmacologically activated AMPK with 5-aminoimidazole-4-carboxamide-1-β-d-ribonucleoside (AICAR). Tetanic contraction in vitro markedly activated the α 1- and α 2-isoforms of AMPK, with a corresponding increase in the rate of 3- O-methylglucose uptake. Incubation with AICAR elicited similar enhancement of AMPK activity and 3- O-methylglucose uptake in rat epitrochlearis muscle. In contrast, whereas contraction stimulated glycogen synthase (GS), AICAR treatment decreased GS activity. Insulin-stimulated GS activity also decreased after AICAR treatment. Whereas contraction activated glycogen phosphorylase (GP), AICAR did not alter GP activity. The muscle glycogen content decreased in response to contraction but was unchanged by AICAR. Lactate release was markedly increased when muscles were stimulated with AICAR in buffer containing glucose, indicating that the glucose taken up into the muscle was catabolized via glycolysis. Our results suggest that AMPK does not mediate contraction-stimulated glycogen synthesis or glycogenolysis in skeletal muscle and also that acute AMPK activation leads to an increased glycolytic flux by antagonizing contraction-stimulated glycogen synthesis.
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Phosphorylation of GS at site 2 (S7) by AMPK inhibits enzyme activity in isolated muscles treated with AICAR.
“This inhibits enzyme activity in isolated muscles treated with AICAR [133-135].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [133]
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Self-citationAto, S., Makanae, Y., Kido, K., Sase, K., Yoshii, N., & Fujita, S. (2017) · Physiological Reports · doi:10.14814/phy2.13364 · Cited by 16 · see citing works
Jakobsen, E., Andersen, J. V., Christensen, S. K., Siamka, O., Larsen, M. R., Waagepetersen, H. S., Aldana, B. I., & Bak, L. K. (2021) · Glia · doi:10.1002/glia.24072 · Cited by 15 · see citing works
Matsunaga, Y., Sakata, Y., Yago, T., Nakamura, H., Shimizu, T., & Takeda, Y. (2018) · Nutrients · doi:10.3390/nu10060753 · Cited by 15 · see citing works
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KATP channel deficiency in mouse FDB causes an impairment of energy metabolism during fatigue
Scott, K. M., Benkhalti, M., Calvert, N. D., Paquette, M., Zhen, L., Harper, M., Al-Dirbashi, O. Y., & Renaud, J. (2016) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00137.2015 · Cited by 13 · see citing works
Miyamoto, L., Yagi, Y., Hatano, A., Kawazoe, K., Ishizawa, K., Minakuchi, K., Tomita, S., & Tsuchiya, K. (2014) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2014.12.006 · Cited by 12 · see citing works
Self-citationMiyamoto, L., Yamane, M., Tomida, Y., Kono, M., Yamaoka, T., Kawasaki, A., Hatano, A., Tsuda, K., Xu, W., Ikeda, Y., et al. (2017) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b17-00316 · Cited by 10 · see citing works
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Guan, Y., Spaulding, H. R., Yu, Q., Zhang, M., Willoughby, O. S., Drake, J. C., & Yan, Z. (2024) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00742.2023 · Cited by 6 · see citing works
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Novel Strategies for Treating Lifestyle-related Diseases Using Various Approaches
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Self-citationBiochemical Measurement of Glycogen: Method to Investigate the AMPK-Glycogen Relationship
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Coptidis Rhizoma Water Extract Stimulates 5′-AMP-Activated Protein Kinase in Rat Skeletal Muscle
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Self-citationCan food factors provide Us with the similar beneficial effects of physical exercise?
Miyamoto, L. (2016) · Food Science and Biotechnology · doi:10.1007/s10068-016-0092-9 · Cited by 3 · see citing works
Self-citationthere any association of metabolic disturbances with joint destruction and pain?
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Central and peripheral mechanisms regulating energy and glucose homeostasis
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Cardiac glycogen accumulation following dexamethasone is regulated by AMPK.
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Self-citationGenetic instability upon the loss of the tumour suppressor folliculin (FLCN)
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- Authors
- Miyamoto, L., Toyoda, T., Hayashi, T., Yonemitsu, S., Nakano, M., Tanaka, S., Ebihara, K., Masuzaki, H., Hosoda, K., Ogawa, Y., Inoue, G., Fushiki, T., & Nakao, K.
- Affiliations
- Kyoto University (JP)
- ORCID
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 2007-03
- Volume
- 102
- Issue
- 3
- Pages
- 1007-1013
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W2168961260
- Cited by
- 72
- References
- 50
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 8 · 2015: 5 · 2014: 5 · 2013: 5 · 2012: 7
- FWCI
- 1.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
- Keywords
- AMPK, skeletal muscle glycogen, glycogen synthase, glycogen phosphorylase, AICAR, muscle contraction, glycolytic flux, lactate release, epitrochlearis muscle, physical activity
- MeSH terms
- Adenosine Triphosphate, Aminoimidazole Carboxamide, Animals, Dose-Response Relationship, Drug, Enzyme Activation, Glucose, Glycogen, Glycogen Synthase, Glycolysis, Insulin, Male, Multienzyme Complexes, Muscle Contraction, Ribonucleosides, Ribonucleotides, Time Factors, Rats, Sprague-Dawley, Protein Serine-Threonine Kinases, Muscle, Skeletal, Lactic Acid, Glycogen Phosphorylase, Rats, AMP-Activated Protein Kinases, In Vitro Techniques
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