The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Muscle glycogen inharmoniously regulates glycogen synthase activity, glucose uptake, and proximal insulin signaling
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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“This hypothesis is based on evidence that muscle glycogen availability is inversely related to muscle cell membrane GLUT4 content during insulin stimulation (Derave et al. 2000), glycogen synthase activity (Jensen et al. 2006), the expression of GLUT4 mRNA (Steinberg et al. 2006), and hence insulin sensitivity (Derave et al. 2000;Jensen et al. 2006;Kawanaka et al. 2000;Laurent et al. 2000;Lither”
From Towards the minimal amount of exercise for improving metabolic health: beneficial effects of reduced-exertion high-intensity interval training (2012) · cites this paper as Jensen et al. 2006
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Self-citationInsulin: The master regulator of glucose metabolism
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Metadata
- 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)
- 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
- 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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