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Regulation of glycogen synthase and phosphorylase activities by glucose and insulin in human skeletal muscle.
Open accessAbstract
We examined the insulin dose-response characteristics of human muscle glycogen synthase and phosphorylase activation. We also determined whether increasing the rate of glucose disposal by hyperglycemia at a fixed insulin concentration activates glycogen synthase. Physiological increments in plasma insulin but not glucose increased the fractional activity of glycogen synthase. The ED50: s for insulin stimulation of whole body and forearm glucose disposal were similar and unaffected by glycemia. Glycogen synthase activation was exponentially related to the insulin-mediated component of whole body and forearm glucose disposal at each glucose concentration. Neither insulin nor glucose changed glycogen phosphorylase activity. These results suggest that insulin but not the rate of glucose disposal per se regulates glycogen synthesis by a mechanism that involves dephosphorylation of glycogen synthase but not phosphorylase. This implies that the low glycogen synthase activities found in insulin-resistant states are a consequence of impaired insulin action rather than reduced glucose disposal.
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“Glycogen synthase is the key insulin-regulated enzyme that controls the rate of muscle glycogen synthesis [148, 150, 200, 212–214].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [212]
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“Glycogen synthase is the key insulin-regulated enzyme that controls the rate of muscle glycogen synthesis [148, 150, 200, 212–214].”
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Metadata
- Authors
- Yki-Järvinen, H., Mott, D., Young, A. A., Stone, K., & Bogardus, C.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Bogardus, C
- Venue
- Journal of Clinical Investigation
- Published
- 1987-07-01
- Volume
- 80
- Issue
- 1
- Pages
- 95-100
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC442206
- OpenAlex
- W2023027042
- Cited by
- 123
- References
- 47
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 1 · 2013: 4 · 2012: 5
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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 › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- glycogen synthase, glycogen phosphorylase, insulin, glucose disposal, skeletal muscle, glycogen synthesis, insulin resistance, enzyme dephosphorylation, hyperglycemia, dose-response relationship, forearm glucose uptake
- MeSH terms
- Adult, Blood Glucose, Enzyme Activation, Glucose, Phosphorylases, Glycogen Synthase, Humans, Insulin, Male, Muscles
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