Cited by 114Metabolism, Diabetes, and CancerGlycogen Storage Diseases and MyoclonusMuscle metabolism and nutrition

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Muscle glycogen inharmoniously regulates glycogen synthase activity, glucose uptake, and proximal insulin signaling

Jensen, Jørgen, Jebens, Einar, Brennesvik, Erlend O., Ruzzin, Jérôme, Soos, Maria A., Engebretsen, Ellen M. L., O'Rahilly, Stephen, Whitehead, Jonathan P.·2006·American Journal of Physiology-Endocrinology and Metabolism

DOI 10.1152/ajpendo.00330.2005

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Abstract

Insulin-stimulated glucose uptake and incorporation of glucose into skeletal muscle glycogen contribute to physiological regulation of blood glucose concentration. In the present study, glucose handling and insulin signaling in isolated rat muscles with low glycogen (LG, 24-h fasting) and high glycogen (HG, refed for 24 h) content were compared with muscles with normal glycogen (NG, rats kept on their normal diet). In LG, basal and insulin-stimulated glycogen synthesis and glycogen synthase activation were higher and glycogen synthase phosphorylation (Ser 645, Ser 649, Ser 653, Ser 657) lower than in NG. GLUT4 expression, insulin-stimulated glucose uptake, and PKB phosphorylation were higher in LG than in NG, whereas insulin receptor tyrosyl phosphorylation, insulin receptor substrate-1-associated phosphatidylinositol 3-kinase activity, and GSK-3 phosphorylation were unchanged. Muscles with HG showed lower insulin-stimulated glycogen synthesis and glycogen synthase activation than NG despite similar dephosphorylation. Insulin signaling, glucose uptake, and GLUT4 expression were similar in HG and NG. This discordant regulation of glucose uptake and glycogen synthesis in HG resulted in higher insulin-stimulated glucose 6-phosphate concentration, higher glycolytic flux, and intracellular accumulation of nonphosphorylated 2-deoxyglucose. In conclusion, elevated glycogen synthase activation, glucose uptake, and GLUT4 expression enhance glycogen resynthesis in muscles with low glycogen. High glycogen concentration per se does not impair proximal insulin signaling or glucose uptake. “Insulin resistance” is observed at the level of glycogen synthase, and the reduced glycogen synthesis leads to increased levels of glucose 6-phosphate, glycolytic flux, and accumulation of nonphosphorylated 2-deoxyglucose.

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Authors: Jensen, J., Jebens, E., Brennesvik, E. O., Ruzzin, J., Soos, M. A., Engebretsen, E. M. L., O'Rahilly, S., & Whitehead, J. P.
Affiliations: National Institute of Occupational Health (NO)
ORCID: Jensen, Jørgen
Ruzzin, Jérôme
Whitehead, Jonathan P.
Venue: American Journal of Physiology-Endocrinology and Metabolism
Publisher: American Physiological Society
Published: 2006-01
Volume: 290
Issue: 1
Pages: E154-E162
ISSN: 0193-1849 (ISSN-L)
1522-1555
DOI: 10.1152/ajpendo.00330.2005
OpenAlex: W2107938341
Cited by: 114
References: 45
Citations by year: 2026: 1 · 2025: 5 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 6 · 2014: 3 · 2013: 4 · 2012: 10
FWCI: 2.89
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: European Commission
Norges Forskningsråd
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Glycogen Storage Diseases and Myoclonus
Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
Keywords: skeletal muscle glycogen, glycogen synthase, glycogen synthase phosphorylation, insulin signaling, glucose uptake, GLUT4, glycogen resynthesis, insulin resistance, glucose-6-phosphate, glycolytic flux, IRS-1, phosphatidylinositol 3-kinase, glycogen synthase kinase-3, fasting and refeeding, blood glucose regulation
MeSH terms: Glycogen Synthase Kinase 3 beta, Animals, Deoxyglucose, Fasting, Glucose, Glycogen, Glycogen Synthase, Glycolysis, Insulin, Male, Phosphorylation, Receptor, Insulin, Signal Transduction, Rats, Wistar, Muscle, Skeletal, Glucose-6-Phosphate, Glycogen Synthase Kinase 3, Proto-Oncogene Proteins c-akt, Glucose Transporter Type 1, Glucose Transporter Type 4, Rats

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Muscle glycogen inharmoniously regulates glycogen synthase activity, glucose uptake, and proximal insulin signaling

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