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Cited by 299Metabolism, Diabetes, and CancerDiabetes, Cardiovascular Risks, and LipoproteinsGlycogen Storage Diseases and Myoclonus

Decreased insulin activation of glycogen synthase in skeletal muscles in young nonobese Caucasian first-degree relatives of patients with non-insulin-dependent diabetes mellitus

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Vaag, A, Henriksen, J E, Beck-Nielsen, H·1992·Journal of Clinical Investigation
DOI 10.1172/jci115656PMC PMC442922
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Abstract

Insulin resistance in non-insulin-dependent diabetes is associated with a defective insulin activation of the enzyme glycogen synthase in skeletal muscles. To investigate whether this may be a primary defect, we studied 20 young (25 +/- 1 yr) Caucasian first-degree relatives (children) of patients with non-insulin-dependent diabetes, and 20 matched controls without a family history of diabetes. Relatives and controls had a normal oral glucose tolerance, and were studied by means of the euglycemic hyperinsulinemic clamp technique, which included performance of indirect calorimetry and muscle biopsies. Insulin-stimulated glucose disposal was decreased in the relatives (9.2 +/- 0.6 vs 11.5 +/- 0.5 mg/kg fat-free mass per (FFM) min, P less than 0.02), and was due to a decreased rate of insulin-stimulated nonoxidative glucose metabolism (5.0 +/- 0.5 vs 7.5 +/- 0.4 mg/kg fat-free mass per min, P less than 0.001). The insulin-stimulated, fractional glycogen synthase activity (0.1/10 mmol liter glucose-6-phosphate) was decreased in the relatives (46.9 +/- 2.3 vs 56.4 +/- 3.2%, P less than 0.01), and there was a significant correlation between insulin-stimulated, fractional glycogen synthase activity and nonoxidative glucose metabolism in relatives (r = 0.76, P less than 0.001) and controls (r = 0.63, P less than 0.01). Furthermore, the insulin-stimulated increase in muscle glycogen content over basal values was lower in the relatives (13 +/- 25 vs 46 +/- 9 mmol/kg dry wt, P = 0.05). We conclude that the defect in insulin activation of muscle glycogen synthase may be a primary, possibly genetically determined, defect that contributes to the development of non-insulin-dependent diabetes.

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  • Lean NGT offspring of two parents with type 2 diabetes exhibit moderate to severe skeletal muscle insulin resistance.

    “Multiple investigators unequivocally have demonstrated that lean NGT offspring of two parents with type 2 diabetes exhibit moderate to severe skeletal muscle insulin resistance ( 28 – 33 ).”

    From Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes (2009) · cites this paper as [31]

    The Subjects section says the participants were nonobese, had normal oral glucose tolerance, and had at least one parent with NIDDM—not necessarily two. The Discussion reports skeletal-muscle insulin resistance but also considerable overlap with controls; it does not establish moderate-to-severe resistance in offspring of two affected parents. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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  • Insulin's ability to stimulate glycogen synthase is diminished in normal glucose-tolerant insulin-resistant relatives of type 2 diabetic individuals.

    “The ability of insulin to stimulate glycogen synthase also is diminished in the normal glucose-tolerant, insulin-resistant relatives of type 2 diabetic individuals [218].”

    From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [218]

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1 retracted

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Research works printed but not linked: 2

  1. [26]26. Bergman, R. N., I. D. Hope, Y. J. Yang, R. M. Watanabe, M. A. Meador, J. H. Youn, and M. Ader. 1989. Assessment ofinsulin sensitivity in vivo: a critical review. Diabetes Metab. Rev. 5:411-429.
  2. [28]28. Lowry, 0. H., and J. V. Passoneau. 1972. A Flexible System ofEnzymatic Analysis. Academic Press, Inc., New York.

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Authors
Vaag, A., Henriksen, J. E., & Beck-Nielsen, H.
Affiliations
Odense University Hospital (DK)
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1992-03-01
Volume
89
Issue
3
Pages
782-788
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci115656
PMC
PMC442922
OpenAlex
W2041249629
Cited by
299
References
58
Citations by year
2026: 2 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 7 · 2017: 2 · 2016: 5 · 2015: 6 · 2014: 3 · 2013: 5 · 2012: 3
FWCI
6.62
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (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 › Rheumatology › Glycogen Storage Diseases and Myoclonus
Keywords
insulin resistance, type 2 diabetes, glycogen synthase, skeletal muscle, first-degree relatives, genetic susceptibility, insulin-stimulated glucose disposal, nonoxidative glucose metabolism, muscle glycogen, hyperinsulinemic-euglycemic clamp
MeSH terms
Adult, Blood Glucose, Diabetes Mellitus, Type 2, Enzyme Activation, Glycogen Synthase, Humans, Insulin, Insulin Resistance, Muscles, White People

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