ArticleThe Journal of clinical investigation1994
Interstitial insulin concentrations determine glucose uptake rates but not insulin resistance in lean and obese men.
Article in The Journal of clinical investigation, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.
- Skin Autofluorescence-Indicated Advanced Glycation End Products as Predictors of Cardiovascular and All-Cause Mortality in High-Risk Subjects: A Systematic Review and Meta-analysis.Journal of the American Heart Association · 2018Pooled it
- Vasodilatory Actions of Glucagon-Like Peptide 1 Are Preserved in Skeletal and Cardiac Muscle Microvasculature but Not in Conduit Artery in Obese Humans With Vascular Insulin Resistance.Diabetes care · 2020 · on this mapTrial
- Insulin resistance of glucose uptake in skeletal muscle cannot be ameliorated by enhancing endothelium-dependent blood flow in obesity.The Journal of clinical investigation · 1998Trial
- The effects of non-insulin-dependent diabetes mellitus on the kinetics of onset of insulin action in hepatic and extrahepatic tissues.The Journal of clinical investigation · 1995Trial
- Endothelial cystathionine-γ-lyase (CTH) regulates body weight and insulin resistance in mice fed a high-fat diet.Redox biology · 2026Article
- Unraveling Skeletal Muscle Insulin Resistance: Molecular Mechanisms and the Restorative Role of Exercise.Circulation research · 2025Review
- Metabolic and vascular insulin resistance: partners in the pathogenesis of cardiovascular disease in diabetes.American journal of physiology. Heart and circulatory physiology · 2025Review
- Microvascular Skeletal-Muscle Crosstalk in Health and Disease.International journal of molecular sciences · 2023Review
- Capillary Endothelial Insulin Transport: The Rate-limiting Step for Insulin-stimulated Glucose Uptake.Endocrinology · 2022Review
- Diabetes pathogenesis and management: the endothelium comes of age.Journal of molecular cell biology · 2021Article
- Heterogeneity in insulin-stimulated glucose uptake among different muscle groups in healthy lean people and people with obesity.Diabetologia · 2021Article
- GLP-1 and insulin regulation of skeletal and cardiac muscle microvascular perfusion in type 2 diabetes.Journal of diabetes · 2020Review
- Transendothelial Insulin Transport is Impaired in Skeletal Muscle Capillaries of Obese Male Mice.Obesity (Silver Spring, Md.) · 2020Article
- Muscle Insulin Resistance and the Inflamed Microvasculature: Fire from Within.International journal of molecular sciences · 2019Review
- Modeling the acute effects of exercise on insulin kinetics in type 1 diabetes.Journal of pharmacokinetics and pharmacodynamics · 2018Article
- Insulin resistance disrupts cell integrity, mitochondrial function, and inflammatory signaling in lymphatic endothelium.Microcirculation (New York, N.Y. : 1994) · 2018Article
- Direct Activation of Angiotensin II Type 2 Receptors Enhances Muscle Microvascular Perfusion, Oxygenation, and Insulin Delivery in Male Rats.Endocrinology · 2018Article
- Insulin Access to Skeletal Muscle is Preserved in Obesity Induced by Polyunsaturated Diet.Obesity (Silver Spring, Md.) · 2018Article
- Insulin access to skeletal muscle is impaired during the early stages of diet-induced obesity.Obesity (Silver Spring, Md.) · 2016Article
- Lipid-induced insulin resistance does not impair insulin access to skeletal muscle.American journal of physiology. Endocrinology and metabolism · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insulin action and obesity are both correlated with the density of muscle capillary supply in humans. Since the altered muscle anatomy in the obese might affect interstitial insulin concentrations and reduce insulin action, we have cannulated peripheral lymphatic vessels in lean and obese males, and compared peripheral lymph insulin concentrations with whole body glucose uptake during a euglycemic, hyperinsulinemic clamp. Lymph insulin concentrations in the lower limb averaged only 34% of arterial insulin concentrations during 150 min of insulin infusion. Obese subjects had the highest arterial (P < or = 0.0001) and lymph insulin (P < 0.005) concentrations, but the lowest glucose uptake rates (P < 0.002). In contrast to the initial steep rise then plateau of arterial insulins, both lymph insulin and whole body glucose uptake rates rose slowly and did not consistently reach a plateau. In each individual, the glucose uptake closely correlated with peripheral lymphatic insulin concentrations (mean r2 = 0.95). The coupling between glucose uptake and lymph insulin (glucose uptake/pmol insulin) was much steeper in lean subjects than in the obese (P < or = 0.0001). These results indicate that even if insulin diffusion into tissues is rate limiting for insulin action, a tissue defect rather than an insulin diffusion defect causes insulin resistance in obese subjects.
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