Transmembrane glucose transport in skeletal muscle of patients with non-insulin-dependent diabetes.
Open accessAbstract
Insulin resistance for glucose metabolism in skeletal muscle is a key feature in non-insulin-dependent diabetes mellitus (NIDDM). Which cellular effectors of glucose metabolism are involved is still unknown. We investigated whether transmembrane glucose transport in vivo is impaired in skeletal muscle in nonobese NIDDM patients. We performed euglycemic insulin clamp studies in combination with the forearm balance technique (brachial artery and deep forearm vein catheterization) in six nonobese NIDDM patients and five age- and weight-matched controls. Unlabeled D-mannitol (a nontransportable molecule) and radioactive 3-O-methyl-D-glucose (the reference molecular probe to assess glucose transport activity) were simultaneously injected into the brachial artery, and the washout curves were measured in the deep venous effluent blood. In vivo transmembrane transport of 3-O-methyl-D-glucose in forearm muscle was determined by computerized analysis of the washout curves. At similar steady-state plasma concentrations of insulin (approximately 500 pmol/liter) and glucose (approximately 5.15 mmol/liter), transmembrane inward transport of 3-O-methyl-D-glucose in skeletal muscle was markedly reduced in the NIDDM patients (6.5 x 10(-2) +/- 0.56 x 10(-2).min-1) compared with controls (12.5 x 10(-2) +/- 1.5 x 10(-2).min-1, P < 0.005). Mean glucose uptake was also reduced in the diabetics both at the whole body level (9.25 +/- 1.84 vs. 28.3 +/- 2.44 mumol/min per kg, P < 0.02) and in the forearm tissues (5.84 +/- 1.51 vs. 37.5 +/- 7.95 mumol/min per kg, P < 0.02). When the latter rates were extrapolated to the whole body level, skeletal muscle accounted for approximately 80% of the defect in insulin action seen in NIDDM patients. We conclude that transmembrane glucose transport, when assessed in vivo in skeletal muscle, is insensitive to insulin in nonobese NIDDM patients, and plays a major role in determining whole body insulin resistance.
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Because of methodologic differences, the results of the triple-tracer technique and MRI studies cannot be reconciled at present.
“Because of methodologic differences, the results of the triple-tracer technique [192, 193] and magnetic resonance imaging [194] studies cannot be reconciled at present.”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [192]
In forearm muscle of lean type 2 diabetics, insulin-stimulated glucose transport is markedly impaired, but intracellular glucose phosphorylation is impaired even more, increasing free intracellular glucose.
“In forearm muscle, insulin-stimulated glucose transport (measured with the triple-tracer technique) is markedly impaired in lean type 2 diabetics [192, 193], but the rate of intracellular glucose phosphorylation is impaired to an even greater extent, resulting in an increase in the free glucose concentration within the intracellular space that is accessible to glucose.”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [192]
Using a triple-tracer technique, insulin-stimulated inward muscle glucose transport in forearm skeletal muscle is severely impaired in type 2 diabetic subjects.
“Using a novel triple-tracer technique, the in vivo dose-response curve for the action of insulin on glucose transport in forearm skeletal muscle has been examined in type 2 diabetic subjects, and insulin-stimulated inward muscle glucose transport has been shown to be severely impaired [192, 193].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [192]
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- Authors
- Bonadonna, R. C., Del Prato, S., Saccomani, M. P., Bonora, E., Gulli, G., Ferrannini, E., Bier, D., Cobelli, C., & DeFronzo, R. A.
- Affiliations
- University of Pisa (IT)
- University of Padua (IT)
- Washington University in St. Louis (US)
- University of Verona (IT)
- Venue
- Journal of Clinical Investigation
- Published
- 1993-07-01
- Volume
- 92
- Issue
- 1
- Pages
- 486-494
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC293636
- OpenAlex
- W2118976195
- Cited by
- 149
- References
- 76
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 4 · 2019: 4 · 2018: 6 · 2016: 5 · 2015: 3 · 2014: 3 · 2013: 4 · 2012: 4
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- University of Washington
- National Institutes of Health (5p41rr000954-34, DK20579)
- Geriatric Research Education and Clinical Center
- National Institute of Diabetes and Digestive and Kidney Diseases (DK20579, DK 24092)
- National Center for Research Resources (RR 00954)
- NIH Clinical Center
- 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
- skeletal muscle, type 2 diabetes, insulin resistance, 3-O-methylglucose, hyperinsulinemic-euglycemic clamp
- MeSH terms
- Adult, Biological Transport, Blood Glucose, Cell Membrane, Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Female, Forearm, Glucose, Humans, Insulin, Insulin Resistance, Male, Muscles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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