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Cited by 142Metabolism, Diabetes, and CancerDiabetes, Cardiovascular Risks, and LipoproteinsGlycogen Storage Diseases and Myoclonus

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Impaired Activation of Glycogen Synthase in People at Increased Risk for Developing NIDDM

Schalin-Jäntti, Camilla, Härkönen, Matti, Groop, Leif C·1992·Diabetes
DOI 10.2337/diab.41.5.598
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Abstract

To study whether impaired activation of muscle glycogen synthase represents an early defect in the pathogenesis of insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM), we quantitated rates of nonoxidative glucose metabolism and measured activities of glycogen synthase and phosphorylase and concentrations of free glucose and glucose-6-phosphate in muscle biopsies, obtained before and after a euglycemic insulin clamp, in 16 NIDDM patients, 18 first-degree relatives of NIDDM patients, and 16 nondiabetic control subjects. Insulin-stimulated glucose storage (20.1 ± 1.5 and 11.6 ± 1.7 vs. 27.9 ± 1.7 βmol·kg−1 lean body mass [LBM]·min−1 P < 0.01–0.001 [3.6 ± 0.3 and 2.1 ± 0.3 vs. 5.0 ± 0.3 mg·kg−1 LBM·min−1] and glycogen synthase activity, measured at 0.1 mM glucose-6-phosphate concentration (11.3 ± 1.3 and 11.6 ± 1.3 vs. 18.3 ± 2.0 nmol·min−1·mg−1 protein, P < 0.01), were impaired in relatives and diabetic subjects compared with control subjects. Glycogen synthase activity correlated with the rate of glucose storage (r = 0.53, P < 0.001). Glycogen phosphorylase fractional activity did not differ among the groups. Apart from increased intramuscular basal glucose concentrations in NIDDM patients, no consistent differences were observed in free glucose and glucose-6-phosphate concentrations between the groups. We conclude that impaired activation of muscle glycogen synthase by insulin is observed in patients with a genetic risk of developing NIDDM and may represent an early defect in the pathogenesis of NIDDM.

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Metadata

Authors
Schalin-Jäntti, C., Härkönen, M., & Groop, L. C.
Affiliations
  • Department of Medicine, Departments of Biochemistry and Clinical Chemistry, Helsinki University Helsinki, Finland
  • University of Helsinki (FI)
ORCID
Groop, Leif C
Venue
Diabetes
Publisher
American Diabetes Association
Published
1992-05-01
Volume
41
Issue
5
Pages
598-604
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diab.41.5.598
OpenAlex
W2155875957
Cited by
142
References
0
Citations by year
2025: 1 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 1 · 2015: 2 · 2014: 1 · 2013: 1
FWCI
4.75
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Funders
Medical Research Council
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Glycogen Storage Diseases and Myoclonus
Keywords
glycogen synthase, insulin resistance, type 2 diabetes, type 2 diabetes risk, first-degree relatives, glycogen phosphorylase, glucose-6-phosphate, hyperinsulinemic-euglycemic clamp, nonoxidative glucose metabolism
MeSH terms
Adult, Biopsy, Diabetes Mellitus, Type 2, Enzyme Activation, Female, Glucose, Glucosephosphates, Phosphorylases, Glycogen Synthase, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Muscles, Risk Factors, Glucose-6-Phosphate

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