Glycogen synthase and phosphofructokinase protein and mRNA levels in skeletal muscle from insulin-resistant patients with non-insulin-dependent diabetes mellitus.
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In patients with non-insulin-dependent diabetes mellitus (NIDDM) and matched control subjects we examined the interrelationships between in vivo nonoxidative glucose metabolism and glucose oxidation and the muscle activities, as well as the immunoreactive protein and mRNA levels of the rate-limiting enzymes in glycogen synthesis and glycolysis, glycogen synthase (GS) and phosphofructokinase (PFK), respectively. Analysis of biopsies of quadriceps muscle from 19 NIDDM patients and 19 control subjects showed in the basal state a 30% decrease (P < 0.005) in total GS activity and a 38% decrease (P < 0.001) in GS mRNA/microgram DNA in NIDDM patients, whereas the GS protein level was normal. The enzymatic activity and protein and mRNA levels of PFK were all normal in diabetic patients. In subgroups of NIDDM patients and control subjects an insulin-glucose clamp in combination with indirect calorimetry was performed. The rate of insulin-stimulated nonoxidative glucose metabolism was decreased by 47% (P < 0.005) in NIDDM patients, whereas the glucose oxidation rate was normal. The PFK activity, protein level, and mRNA/microgram DNA remained unchanged. The relative activation of GS by glucose-6-phosphate was 33% lower (P < 0.02), whereas GS mRNA/micrograms DNA was 37% lower (P < 0.05) in the diabetic patients after 4 h of hyperinsulinemia. Total GS immunoreactive mass remained normal. In conclusion, qualitative but not quantitative posttranslational abnormalities of the GS protein in muscle determine the reduced insulin-stimulated nonoxidative glucose metabolism in NIDDM.
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Insulin has no effect on muscle PFK activity, mRNA levels, or protein content in either nondiabetic or diabetic individuals.
“Insulin has no effect on muscle PFK activity, mRNA levels, or protein content in either nondiabetic or diabetic individuals [221].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [221]
Glycogen synthase mRNA and protein levels are decreased in muscle of type 2 diabetic patients, partly explaining decreased glycogen synthase activity.
“Glycogen synthase mRNA and protein levels, however, are decreased in muscle of type 2 diabetic patients, partly explaining the decreased glycogen synthase activity [221, 222].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [221]
Most studies show insulin does not increase glycogen synthase mRNA or protein expression in human muscle.
“Most studies have demonstrated that insulin does not increase glycogen synthase mRNA or protein expression in human muscle [201, 220, 221].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [221]
Most evidence indicates that PFK activity is normal in skeletal muscle of type 2 diabetic subjects.
“most evidence indicates that the activity of PFK is normal [216, 221].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [221]
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Self-citation
- Authors
- Vestergaard, H., Lund, S., Larsen, F. S., Bjerrum, O. J., & Pedersen, O.
- Affiliations
- Steno Diabetes Center Copenhagen (DK)
- Novo Nordisk (Denmark) (DK)
- Venue
- Journal of Clinical Investigation
- Published
- 1993-06-01
- Volume
- 91
- Issue
- 6
- Pages
- 2342-2350
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC443291
- OpenAlex
- W2019407986
- Cited by
- 98
- References
- 64
- Citations by year
- 2022: 1 · 2021: 1 · 2019: 1 · 2018: 3 · 2017: 2 · 2015: 5 · 2014: 2 · 2013: 2 · 2012: 2
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- 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
- glycogen synthase, phosphofructokinase, type 2 diabetes, insulin resistance, skeletal muscle, nonoxidative glucose metabolism, glucose oxidation, glucose-6-phosphate, post-translational modification, hyperinsulinemia, quadriceps
- MeSH terms
- Adult, Aerobiosis, Aged, Anaerobiosis, Diabetes Mellitus, Type 2, Female, Glucose, Glycogen Synthase, Humans, Insulin Resistance, Male, Metabolic Clearance Rate, Middle Aged, Muscles, Oxidation-Reduction, Phosphofructokinase-1, RNA, Messenger, Glucose Clamp Technique, White People, Lipid Metabolism
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