Cited by 357Metabolism, Diabetes, and CancerDiabetes, Cardiovascular Risks, and LipoproteinsAdipokines, Inflammation, and Metabolic Diseases

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Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes.

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Nikoulina, S E, Ciaraldi, T P, Mudaliar, S, Mohideen, P, Carter, L, Henry, R R·2000·Diabetes

DOI 10.2337/diabetes.49.2.263

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Abstract

Glycogen synthase (GS) activity is reduced in skeletal muscle of type 2 diabetes, despite normal protein expression, consistent with altered GS regulation. Glycogen synthase kinase-3 (GSK-3) is involved in regulation (phosphorylation and deactivation) of GS. To access the potential role of GSK-3 in insulin resistance and reduced GS activity in type 2 diabetes, the expression and activity of GSK-3 were studied in biopsies of vastus lateralis from type 2 and nondiabetic subjects before and after 3-h hyperinsulinemic (300 mU x m(-2) x min(-1))-euglycemic clamps. The specific activity of GSK-3alpha did not differ between nondiabetic and diabetic muscle and was decreased similarly after 3-h insulin infusion. However, protein levels of both alpha and beta isoforms of GSK-3 were elevated (approximately 30%) in diabetic muscle compared with lean (P < 0.01) and weight-matched obese nondiabetic subjects (P < 0.05) and were unchanged by insulin infusion. Thus, both basal and insulin-stimulated total GSK-3 activities were elevated by approximately twofold in diabetic muscle. GSK-3 expression was related to in vivo insulin action, as GSK-3 protein was negatively correlated with maximal insulin-stimulated glucose disposal rates. In summary, GSK-3 protein levels and total activities are 1) elevated in type 2 diabetic muscle independent of obesity and 2) inversely correlated with both GS activity and maximally insulin-stimulated glucose disposal. We conclude that increased GSK-3 expression in diabetic muscle may contribute to the impaired GS activity and skeletal muscle insulin resistance present in type 2 diabetes.

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Background
Cellular Mechanisms of Insulin Action
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Intrarenal and Urinary Glycogen Synthase Kinase-3 Beta Levels in Diabetic and Nondiabetic Chronic Kidney Disease
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Background
Classical PKC is not associated with defective insulin signaling in patients with impaired glucose tolerance
Kim, D. M., Jang, H. J., Han, S. J., Ha, E. S., Kim, Y. K., Park, J. W., Song, K. E., Jung, S. H., Ahn, S. M., Choi, S. E., et al. (2009) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2008.11.035 · Cited by 5
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“A separate study in the literature found that significantly increased expression of GSK3 in the skeletal muscle of type 2 diabetes patients led to impaired glycogen synthase (GS) activity and contributed to insulin resistance in skeletal muscle [30].”
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Background
The SIRT3/GSK-3β/GLUT4 axis might be involved in maternal hypoxia-induced skeletal muscle insulin resistance in old male rat offspring
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Background
Insulin signaling and pharmacology in humans and in corals
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Background
Can the inhibition of glycogen synthase kinase 3 mimic the physiological effects of exercise on muscle and other organs?
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Authors: Nikoulina, S. E., Ciaraldi, T. P., Mudaliar, S., Mohideen, P., Carter, L., & Henry, R. R.
Affiliations: University of California San Diego (US)
ORCID: Ciaraldi, T P
Mudaliar, S
Henry, R R
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2000-02-01
Volume: 49
Issue: 2
Pages: 263-271
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diabetes.49.2.263
OpenAlex: W2098017074
Cited by: 357
References: 0
Citations by year: 2026: 6 · 2025: 9 · 2024: 8 · 2023: 10 · 2022: 13 · 2021: 24 · 2020: 13 · 2019: 16 · 2018: 17 · 2017: 22 · 2016: 13 · 2015: 12 · 2014: 12 · 2013: 15 · 2012: 10
FWCI: 3.97
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Funders: National Center for Research Resources (MO1 RR00827, M01RR000827)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: glycogen synthase kinase-3, type 2 diabetes, skeletal muscle insulin resistance, glycogen synthase, GSK3α, GSK3β, insulin-stimulated glucose disposal, hyperinsulinemic-euglycemic clamp, vastus lateralis, obesity
MeSH terms: Adult, Diabetes Mellitus, Type 2, Glycogen Synthase, Humans, Insulin, Insulin Resistance, Isoenzymes, Middle Aged, Phosphorylation, Reference Values, Calcium-Calmodulin-Dependent Protein Kinases, Muscle, Skeletal, Glycogen Synthase Kinases, Glycogen Synthase Kinase 3

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Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes.

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