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Impaired Activation of Glycogen Synthase in People at Increased Risk for Developing NIDDM
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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“Similarly, there is no evidence that an alteration in glycogen phosphorylase plays any role in the abnormality in glycogen formation in type 2 diabetes [228].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [228]
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Pathogenesis of type 2 diabetes mellitus
DeFronzo, R. A. (2004) · Medical Clinics of North America · doi:10.1016/j.mcna.2004.04.013 · Cited by 1,342
Perseghin, G., Price, T. B., Petersen, K. F., Roden, M., Cline, G. W., Gerow, K., Rothman, D. L., & Shulman, G. I. (1996) · New England Journal of Medicine · doi:10.1056/nejm199610313351804 · Cited by 699
Pathogenesis of insulin resistance in skeletal muscle
Abdul-Ghani, M. A., & DeFronzo, R. A. (2010) · Journal of Biomedicine and Biotechnology · doi:10.1155/2010/476279 · Cited by 670
Gerich, J. E. (1998) · Endocrine Reviews · doi:10.1210/edrv.19.4.0338 · Cited by 450
Ivy, J. L. (1997) · Sports Medicine · doi:10.2165/00007256-199724050-00004 · Cited by 369
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
- 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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