Effects of insulin infusion on human skeletal muscle pyruvate dehydrogenase, phosphofructokinase, and glycogen synthase. Evidence for their role in oxidative and nonoxidative glucose metabolism.

Mandarino, L J; Wright, K S; Verity, L S; Nichols, J; Bell, J M; Kolterman, O G; Beck-Nielsen, H

doi:10.1172/jci113118

Cited by 194Metabolism, Diabetes, and CancerMuscle metabolism and nutritionDiabetes, Cardiovascular Risks, and Lipoproteins

Effects of insulin infusion on human skeletal muscle pyruvate dehydrogenase, phosphofructokinase, and glycogen synthase. Evidence for their role in oxidative and nonoxidative glucose metabolism.

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Mandarino, L J, Wright, K S, Verity, L S, Nichols, J, Bell, J M, Kolterman, O G, Beck-Nielsen, H·1987·Journal of Clinical Investigation

DOI 10.1172/jci113118PMC PMC442287

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Abstract

To determine whether activation by insulin of glycogen synthase (GS), phosphofructokinase (PFK), or pyruvate dehydrogenase (PDH) in skeletal muscle regulates intracellular glucose metabolism, subjects were studied basally and during euglycemic insulin infusions of 12, 30, and 240 mU/m2 X min. Glucose disposal, oxidative and nonoxidative glucose metabolism were determined. GS, PFK, and PDH were assayed in skeletal muscle under each condition. Glucose disposal rates were 2.37 +/- 0.11, 3.15 +/- 0.19, 6.71 +/- 0.44, and 11.7 +/- 1.73 mg/kg X min; glucose oxidation rates were 1.96 +/- 0.18, 2.81 +/- 0.28, 4.43 +/- 0.32, and 5.22 +/- 0.52. Nonoxidative glucose metabolism was 0.39 +/- 0.13, 0.34 +/- 0.26, 2.28 +/- 0.40, and 6.52 +/- 1.21 mg/kg X min. Both the proportion of active GS and the proportion of active PDH were increased by hyperinsulinemia. PFK activity was unaffected. Activation of GS was correlated with nonoxidative glucose metabolism, while activation of PDH was correlated with glucose oxidation. Sensitivity to insulin of GS was similar to that of nonoxidative glucose metabolism, while the sensitivity to insulin of PDH was similar to that of glucose oxidation. Therefore, the activation of these enzymes in muscle may regulate nonoxidative and oxidative glucose metabolism.

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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 [216]
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 [216]

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Authors: Mandarino, L. J., Wright, K. S., Verity, L. S., Nichols, J., Bell, J. M., Kolterman, O. G., & Beck-Nielsen, H.
Affiliations: San Diego State University (US)
ORCID: Mandarino, L J
Kolterman, O G
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1987-09-01
Volume: 80
Issue: 3
Pages: 655-663
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci113118
PMC: PMC442287
OpenAlex: W2042254778
Cited by: 194
References: 42
Citations by year: 2025: 2 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 4 · 2015: 6 · 2014: 3 · 2013: 2 · 2012: 5
FWCI: 3.17
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Diabetes Association
National Center for Research Resources (RR00827)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: insulin, skeletal muscle, pyruvate dehydrogenase, phosphofructokinase, glycogen synthase, glucose metabolism, glucose disposal, glucose oxidation, nonoxidative glucose metabolism, hyperinsulinemia, enzyme activation, insulin sensitivity
MeSH terms: Glucose, Glycogen Synthase, Humans, Insulin, Muscles, Oxidation-Reduction, Phosphofructokinase-1, Pyruvate Dehydrogenase Complex, Lipid Metabolism

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Effects of insulin infusion on human skeletal muscle pyruvate dehydrogenase, phosphofructokinase, and glycogen synthase. Evidence for their role in oxidative and nonoxidative glucose metabolism.

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