New Insights Into the Role and Mechanism of Glycogen Synthase Activation by Insulin

Lawrence, John C; Roach, Peter J

doi:10.2337/diab.46.4.541

Cited by 311Metabolism, Diabetes, and CancerGlycogen Storage Diseases and MyoclonusProtein Kinase Regulation and GTPase Signaling

New Insights Into the Role and Mechanism of Glycogen Synthase Activation by Insulin

Lawrence, John C, Roach, Peter J·1997·Diabetes

DOI 10.2337/diab.46.4.541

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Abstract

The metabolism of the storage polysaccharide glycogen is intimately linked with insulin action and blood glucose homeostasis. Insulin activates both glucose transport and glycogen synthase in skeletal muscle. The central issue of a long-standing debate is which of these two effects determines the rate of glycogen synthesis in response to insulin. Recent studies with transgenic animals indicate that, under appropriate conditions, each process can contribute to determining the extent of glycogen accumulation. Insulin causes stable activation of glycogen synthase by promoting dephosphorylation of multiple sites in the enzyme. A model linking this action to the mitogen-activated protein kinase signaling pathway via the phosphorylation of the regulatory subunit of glycogen synthase phosphatase gained widespread acceptance. However, the most recent evidence argues strongly against this mechanism. A newer model, in which insulin inactivates the enzyme glycogen synthase kinase-3 via the protein kinase B pathway, has emerged. Though promising, this model still does not completely explain the molecular basis for the insulin-mediated activation of glycogen synthase, which remains one of the many unknowns of insulin action.

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GSK-3 phosphorylates Ser645, Ser649, Ser653, Ser657 of glycogen synthase, which are the most important sites for regulation of glycogen synthase activity.
“GSK-3 phosphorylates these sites, which are the most important for regulation of glycogen synthase activity [11]”
From Glucocorticoid-induced insulin resistance in skeletal muscles: defects in insulin signalling and the effects of a selective glycogen synthase kinase-3 inhibitor (2005) · cites this paper as [11]

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Authors: Lawrence, J. C., & Roach, P. J.
Affiliations: University of Virginia (US)
Indiana University Indianapolis (US)
Venue: Diabetes
Publisher: American Diabetes Association
Published: 1997-04-01
Volume: 46
Issue: 4
Pages: 541-547
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diab.46.4.541
OpenAlex: W2140664543
Cited by: 311
References: 0
Citations by year: 2026: 1 · 2025: 4 · 2024: 8 · 2023: 3 · 2022: 7 · 2021: 8 · 2020: 3 · 2019: 6 · 2018: 4 · 2017: 6 · 2016: 6 · 2015: 4 · 2014: 10 · 2013: 3 · 2012: 14
FWCI: 7.00
Type: journal article
Language: en
Open access: closed
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (1zicar041189-01)
National Institute of Diabetes and Digestive and Kidney Diseases (DK28312, DK 27221, R01DK028312)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR41189)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords: glycogen synthase, insulin signaling, glycogen synthesis, glycogen synthase kinase-3, Akt, mitogen-activated protein kinase, glycogen synthase phosphatase, glucose transport, skeletal muscle, blood glucose homeostasis
MeSH terms: Animals, Enzyme Activation, Glycogen, Glycogen Synthase, Humans, Insulin, Muscle, Skeletal

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New Insights Into the Role and Mechanism of Glycogen Synthase Activation by Insulin

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