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Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance
Open accessAbstract
To test the hypothesis that obesity/insulin resistance impairs both endothelium-dependent vasodilation and insulin-mediated augmentation of endothelium-dependent vasodilation, we studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of methacholine chloride (MCh) or sodium nitroprusside (SNP) during saline infusion and euglycemic hyperinsulinemia in lean insulin-sensitive controls (C), in obese insulin-resistant subjects (OB), and in subjects with non-insulin-dependent diabetes mellitus (NIDDM). MCh induced increments in LBF were approximately 40% and 55% lower in OB and NIDDM, respectively, as compared with C (P < 0.05). Euglycemic hyperinsulinemia augmented the LBF response to MCh by - 50% in C (P < 0.05 vs saline) but not in OB and NIDDM. SNP caused comparable increments in LBF in all groups. Regression analysis revealed a significant inverse correlation between the maximal LBF change in response to MCh and body fat content. Thus, obesity/insulin resistance is associated with (a) blunted endothelium-dependent, but normal endothelium-independent vasodilation and (b) failure of euglycemic hyperinsulinemia to augment endothelium-dependent vasodilation. Therefore, obese/insulin-resistant subjects are characterized by endothelial dysfunction and endothelial resistance to insulin's effect on enhancement of endothelium-dependent vasodilation. This endothelial dysfunction could contribute to the increased risk of atherosclerosis in obese insulin-resistant subjects.
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“Furthermore, IR per se has a direct impact on endothelial function, distinct from effects related to unfavorable changes in lipid composition or blood pressure (9).”
From Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus (2001) · cites this paper as [9]
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InfluentialVasodilation With Sodium Nitroprusside Does Not Improve Insulin Action in Essential Hypertension
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“This population exhibits a high prevalence of insulin resistance, a disorder that is positively associated with endothelial dysfunction (Caballero, 2003; Steinberg et al., 1996).”
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“Similarly, in the obese human, in the absence of hypertension or diabetes, insulin resistance is also associated with impaired endothelium dependent vasodilation that is not corrected by the in vivo administration of insulin.(28)”
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“Endothelial dysfunction represents the earliest abnormality in the development of vascular diseases and is associated with a number of traditional risks factors including diabetes mellitus, hypercholesterolemia, hypertension, insulin resistance, advanced age and obesity [76].”
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“An increase in the activity of the sympathetic nervous system with development of the individual pathologies comprising the metabolic syndrome X in both humans and in animal models has reported repeatedly (10, 19, 22, 25, 27, 37, 40, 45), and this has commonly been associated with the development of hypertension.”
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“A large body of evidence in humans indicates that endothelial dysfunction is closely associated with alteration of large vessels and atherosclerosis in type 2 diabetes [11, 22–25].”
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“Elevation of circulating free fatty acids (FFAs), experimentally or as seen in obese insulin-resistant individuals and in type 2 diabetes, results in 40% to 50% lower endothelium-dependent vasodilation.(3,4) The elevation of circulating FFA in obesity, metabolic syndrome, and type 2 diabetes is associated with impaire…”
BackgroundEffects of Resistance Training on Obese Adolescents
Dias, I., Farinatti, P., de Souza, M. D. G. C., Manhanini, D. P., Balthazár, E., DANTAS, D. L. S., PINTO, E. H. D. A., Bouskela, E., & Kraemer‐Aguiar, L. G. (2015) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000705 · Cited by 57
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Endothelial Dysfunction Aassociated with Hypercortisolism is Reversible in Cushing's Syndrome
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“ENDOTHELIAL FUNCTION IN OBESITY We and others have measured vascular function in lean and obese subjects.(6,7,22) Our group used the thermodilution technique to assess changes in leg blood flow in response to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride.”
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Metadata
- Authors
- Steinberg, H. O., Chaker, H., Leaming, R., Johnson, A., Brechtel, G., & Baron, A. D.
- Affiliations
- Indiana University (US)
- Richard L. Roudebush VA Medical Center (US)
- Indiana University Hospital (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1996-06-01
- Volume
- 97
- Issue
- 11
- Pages
- 2601-2610
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC507347
- OpenAlex
- W1982811953
- Cited by
- 1,687
- References
- 59
- Citations by year
- 2026: 11 · 2025: 23 · 2024: 17 · 2023: 30 · 2022: 19 · 2021: 32 · 2020: 30 · 2019: 36 · 2018: 36 · 2017: 46 · 2016: 50 · 2015: 51 · 2014: 69 · 2013: 69 · 2012: 61
- FWCI
- 18.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- American Heart Association
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK42469, P60DK020542, DK20542)
- National Center for Research Resources (M 01-RR750-19)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- obesity, insulin resistance, endothelial dysfunction, endothelium-dependent vasodilation, euglycemic hyperinsulinemia, leg blood flow, methacholine, sodium nitroprusside, type 2 diabetes, fat mass, atherosclerosis risk
- MeSH terms
- Adult, Blood Glucose, Blood Pressure, Cholesterol, Diabetes Mellitus, Type 2, Endothelium, Vascular, Fatty Acids, Nonesterified, Glucose, Humans, Hyperinsulinism, Infusions, Intra-Arterial, Infusions, Intravenous, Insulin, Insulin Resistance, Leg, Cholesterol, HDL, Cholesterol, LDL, Nitroprusside, Obesity, Reference Values, Regional Blood Flow, Syndrome, Time Factors, Triglycerides, Vasodilation, Glucose Clamp Technique, Body Mass Index, Methacholine Chloride
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