ArticleThe Journal of clinical endocrinology and metabolism1991
Mechanism of insulin resistance in insulin-dependent diabetes mellitus: a major role for reduced skeletal muscle blood flow.
Article in The Journal of clinical endocrinology and metabolism, 1991. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 62 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Effect of Metformin on Insulin Sensitivity and Pan-Arterial Vascular Function in Adults With Metabolic Syndrome
Effect of GLP-1 on Microvascular Insulin Responses in Type 1 Diabetes
Who cites it
62 citing papers in PubMed, 214 citations in OpenAlex.
- Beneficial vascular effects of oral phosphatidylserine supplementation in type 2 diabetes.Journal of applied physiology (Bethesda, Md. : 1985) · 2026Trial
- Insulin-mediated muscle microvascular perfusion and its phenotypic predictors in humans.Scientific reports · 2021 · on this mapTrial
- Role of blood flow in regulating insulin-stimulated glucose uptake in humans. Studies using bradykinin, [15O]water, and [18F]fluoro-deoxy-glucose and positron emission tomography.The Journal of clinical investigation · 1996Trial
- Metabolic effects of lacidipine: a placebo-controlled study using the euglycaemic hyperinsulinaemic clamp.British journal of clinical pharmacology · 1993Trial
- Metabolic and vascular insulin resistance: partners in the pathogenesis of cardiovascular disease in diabetes.American journal of physiology. Heart and circulatory physiology · 2025Review
- Insulin Resistance in Type 1 Diabetes: Pathophysiological, Clinical, and Therapeutic Relevance.Endocrine reviews · 2025Review
- JunB condensation attenuates vascular endothelial damage under hyperglycemic condition.Journal of molecular cell biology · 2024Article
- Empagliflozin improves vascular insulin sensitivity and muscle perfusion in persons with type 2 diabetes.American journal of physiology. Endocrinology and metabolism · 2024Article
- Neuraminidase-induced externalization of phosphatidylserine activates ADAM17 and impairs insulin signaling in endothelial cells.American journal of physiology. Heart and circulatory physiology · 2024Article
- Insulin-induced vasoconstriction is prevalent in muscle microvasculature of otherwise healthy persons with type 1 diabetes.American journal of physiology. Endocrinology and metabolism · 2023Article
- Sympathetic transduction to blood pressure during euglycemic-hyperinsulinemia in young healthy adults: role of burst amplitude.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Article
- Impact of sex and diet-induced weight loss on vascular insulin sensitivity in type 2 diabetes.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Article
- Vascular deficits contributing to skeletal fragility in type 1 diabetes.Frontiers in clinical diabetes and healthcare · 2023Review
- New insights into mechanisms of endothelial insulin resistance in type 2 diabetes.American journal of physiology. Heart and circulatory physiology · 2022Review
- Involvement of the extracellular matrix and integrin signalling proteins in skeletal muscle glucose uptake.The Journal of physiology · 2022Review
- ADAM17 cleaves the insulin receptor ectodomain on endothelial cells and causes vascular insulin resistance.American journal of physiology. Heart and circulatory physiology · 2022Article
- Role of the Autonomic Nervous System in the Hemodynamic Response to Hyperinsulinemia-Implications for Obesity and Insulin Resistance.Current diabetes reports · 2022Review
- Role of the arterial baroreflex in the sympathetic response to hyperinsulinemia in adult humans.American journal of physiology. Endocrinology and metabolism · 2022Article
- 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
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 4 institutions in 1 country.
Funding
Abstract
To define the kinetic mechanisms of insulin resistance (IR) in insulin-dependent diabetes (IDDM), we studied seven control (C) and five IDDM (glycohemoglobin, 14 +/- 2+) men matched for age (36 +/- 2 vs. 37 +/- 3 yr), lean body mass (59 +/- 2 vs. 58 +/- 3 kg), and leg volume (mean +/- SEM, 10.4 +/- 0.3 vs. 9.8 +/- 0.5 L). Maximal capacity (Vmax) and affinity (Km) for glucose uptake in whole body (WBGU) and leg skeletal muscle (LGU) were measured during a 120 mU/m2.min insulin infusion, and blood glucose was clamped at about 4, 7, 12, and 21 mmol/L. LGU = femoral arterio-venous glucose difference (FAVGD) X leg blood flow (LBF). Compared to C, IDDMs had about 35% lower rates of WBGU at all glucose levels (P less than 0.01). The FAVGD (millimoles per L) in C vs. IDDM was 1.23 +/- 0.05 vs. 1.06 +/- 0.09, 2.44 +/- 0.11 vs. 2.24 +/- 0.16, 2.91 +/- 0.18 vs. 2.91 +/- 0.30, and 3.27 +/- 0.12 vs. 3.35 +/- 0.4 (P = NS at each glucose). LBF (decaliters per min) was reduced in IDDM vs. C [2.8 +/- 0.5 vs. 4.3 +/- 0.4 (P less than 0.05), 3.1 +/- 0.4 vs. 5.1 +/- 0.7 (P less than 0.05), 2.7 +/- 0.2 vs. 6.3 +/- 0.8 (P less than 0.01), and 3.1 +/- 0.7 vs. 6.5 +/- 0.8 (P less than 0.01) at each glucose level]. Kinetic analysis revealed that 1) the Vmax for WBGU and LGU were reduced in IDDM vs. C (P less than 0.05), and 2) the Vmax for skeletal muscle glucose extraction (FAVGD) was identical in C and IDDM (3.6 mmol/L). The Km values for WBGU, LGU, and glucose extraction were not different in C and IDDM (approximately 6 mmol/L). Thus, in IDDM 1) decreased glucose uptake is due to reduced skeletal muscle glucose uptake; 2) muscle glucose extraction is normal, but blood flow is reduced; and thus, 3) in IDDM, IR is due to reduced glucose and insulin delivery (blood flow) to skeletal muscle. This represents a novel mechanism for in vivo IR.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.