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Hyperglycemia normalizes insulin-stimulated skeletal muscle glucose oxidation and storage in noninsulin-dependent diabetes mellitus.
Open accessAbstract
The diminished ability of insulin to promote glucose disposal and storage in muscle has been ascribed to impaired activation of glycogen synthase (GS). It is possible that decreased glucose storage could occur as a consequence of decreased glucose uptake, and that GS is impaired secondarily. Muscle glucose uptake in 15 diabetic subjects was matched to 15 nondiabetic subjects by maintaining fasting hyperglycemia during infusion of insulin. Leg muscle glucose uptake, glucose oxidation (local indirect calorimetry), release of glycolytic products, and muscle glucose storage, as well as muscle GS and pyruvate dehydrogenase (PDH) were determined before and during insulin infusion. Basal leg glucose oxidation and PDH were increased in the diabetics. Insulin-stimulated leg glucose uptake in the diabetics (8.05 +/- 1.41 mumol/[min.100 ml leg tissue]) did not differ from controls (5.64 +/- 0.37). Insulin-stimulated leg glucose oxidation, nonoxidized glycolysis, and glucose storage (2.48 +/- 0.27, 0.68 +/- 0.15, and 5.04 +/- 1.34 mumol/[min.100 ml], respectively) were not different from controls (2.18 +/- 0.12, 0.62 +/- 0.16, and 2.83 +/- 0.31). PDH and GS in noninsulin-dependent diabetes mellitus (NIDDM) were also normal during insulin infusion. When diabetics were restudied after being rendered euglycemic by overnight insulin infusion, GS and PDH were reduced compared with hyperglycemia. Thus, fasting hyperglycemia is sufficient to normalize insulin-stimulated muscle glucose uptake in NIDDM, and glucose is distributed normally to glycogenesis and glucose oxidation, possibly by normalization of GS and PDH.
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“Further support for these findings comes from studies in which glucose disposal rates were matched by increasing the glucose or insulin infusion rates ([27](#r27), [66](#r66)).”
From Metabolic flexibility and insulin resistance (2008) · cites this paper as [27]
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Cited by
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Mechanisms of fatty acid-induced inhibition of glucose uptake.
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“Adapted from Kelley and Mandarino (21) and Kelley et al.”
BackgroundMethodInfluentialSelf-citationMetabolic Flexibility in Health and Disease
Goodpaster, B. H., & Sparks, L. M. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.04.015 · Cited by 995
Comprehensive review on lactate metabolism in human health
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“In response to insulin infusion, lactate output from the skeletal muscle has been reported similar in diabetic patients and in healthy subjects in some studies (Juel et al., 2004; Kelley and Mandarino, 1990) while others find that the interstitialmuscle lactate concentration does not increase significantly during the…”
BackgroundResultInfluentialExercise and Insulin Sensitivity: A Review
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Metadata
- Authors
- Kelley, D. E., & Mandarino, L. J.
- Affiliations
- University of Pittsburgh (US)
- United States Department of Veterans Affairs (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1990-12-01
- Volume
- 86
- Issue
- 6
- Pages
- 1999-2007
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC329837
- OpenAlex
- W2171543951
- Cited by
- 210
- References
- 37
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 6 · 2019: 6 · 2018: 4 · 2017: 5 · 2016: 3 · 2015: 5 · 2014: 5 · 2013: 4 · 2012: 8
- FWCI
- 2.85
- 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
- Research to Prevent Blindness
- Deutsches Krebsforschungszentrum
- National Institutes of Health (5r01dk041075-03)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK41075)
- National Center for Research Resources (M01RR000056)
- 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 › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- hyperglycemia, type 2 diabetes, muscle glucose uptake, glycogen synthase, pyruvate dehydrogenase, insulin resistance, glycogen synthesis, glycolysis
- MeSH terms
- Alanine, Calorimetry, Diabetes Mellitus, Type 2, Glucose, Glycogen Synthase, Glycolysis, Humans, Hyperglycemia, Insulin, Lactates, Leg, Lipid Mobilization, Muscles, Pyruvate Dehydrogenase Complex
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