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Reduced glycogen synthase activity in skeletal muscle from obese patients with and without Type 2 (non-insulin-dependent) diabetes mellitus

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Damsbo, P., Vaag, A., Hother-Nielsen, O., Beck-Nielsen, H.·1991·Diabetologia
DOI 10.1007/bf00405082
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Abstract

In order to evaluate the importance of a defect in insulin mediated non-oxidative glucose metabolism and glycogen synthase activity in skeletal muscles in obese subjects with and without Type 2 (non-insulin-dependent) diabetes mellitus we studied: 10 lean and 10 obese control subjects and 12 obese diabetic patients using the euglycaemic hyperinsulinaemic clamp technique (basal, 20 mU.(m2)-1.min-1, 80 mU.(m2)-1.min-1) in combination with indirect calorimetry. Muscle biopsies were taken from m. vastus lateralis at each insulin level. We found that non-oxidative glucose metabolism could be stimulated by insulin in all three groups (p less than 0.01). The values obtained at the highest insulin levels (around 140 microU/ml) were lower in both obese groups compared to the lean control subjects (118 +/- 21, 185 +/- 31, 249 +/- 14 mg.(m2)-1.min-1 (p less than 0.01]. Insulin stimulation of the glycogen synthase activity at a glucose-6-phosphate concentration of 0.1 mmol/l was absent in both obese groups, while activities increased significantly in the lean control subjects (19.6 +/- 4.2% to 45.6 +/- 6.8%, p less than 0.01). Glycogen synthase activities at the highest insulin concentrations only differed significantly between lean control subjects and obese diabetic patients (45 +/- 7% and 31 +/- 5%, p less than 0.05). We conclude that insulin resistance in peripheral tissues in obese subjects with and without Type 2 diabetes may be partly explained by a reduced insulin mediated non-oxidative glucose metabolism and that this abnormality might be due to an absent insulin stimulation of glycogen synthase in skeletal muscles. This enzyme defect is correlated to obesity itself.

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  • Under basal conditions, total glycogen synthase activity in type 2 diabetic subjects is reduced, and insulin's ability to activate glycogen synthase is severely impaired.

    “Under basal conditions, total glycogen synthase activity in type 2 diabetic subjects is reduced, and the ability of insulin to activate glycogen synthase is severely impaired [7, 215–217].”

    From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [215]

  • Type 2 diabetes is characterized in skeletal muscle by a reduction in glucose uptake, decreased glycogen synthesis, down regulation of fat oxidation and an expanded intramuscular triacylglycerol pool.

    “T2D is characterized in skeletal muscle by a reduction in glucose uptake, decreased glycogen synthesis, down regulation of fat oxidation and an expanded intramuscular (TAG) pool [108,109].”

    From Omega-3 Fatty Acids and Skeletal Muscle Health (2015) · cites this paper as [108]

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Authors
Damsbo, P., Vaag, A., Hother-Nielsen, O., & Beck-Nielsen, H.
Affiliations
  • Hvidovre Hospital (DK)
  • Odense University Hospital (DK)
ORCID
Vaag, A.
Venue
Diabetologia
Publisher
Springer Science and Business Media LLC
Published
1991-04
Volume
34
Issue
4
Pages
239-245
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
DOI
10.1007/bf00405082
OpenAlex
W2041814414
Cited by
203
References
31
Citations by year
2025: 3 · 2024: 2 · 2023: 2 · 2022: 3 · 2020: 1 · 2019: 3 · 2018: 6 · 2017: 3 · 2016: 1 · 2015: 5 · 2014: 2 · 2013: 4 · 2012: 7
FWCI
2.91
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Diabetologia (publishedVersion)
  • PubMed (publishedVersion)
Funders
Diabetesforeningen
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 › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
glycogen synthase, skeletal muscle, type 2 diabetes, obesity, insulin resistance, insulin-stimulated glucose uptake, glucose-6-phosphate, vastus lateralis, hyperinsulinemic-euglycemic clamp
MeSH terms
Allosteric Regulation, Diabetes Mellitus, Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Female, Glycogen Synthase, Humans, Insulin, Insulin Infusion Systems, Kinetics, Male, Middle Aged, Muscles, Obesity, Reference Values, Glucose Clamp Technique

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