Insulin Causes Endothelial Dysfunction in Humans: Sites and Mechanisms
Abstract
Background Insulin resistance is often accompanied by hyperinsulinemia and may predispose to atherosclerosis. Endothelium plays a central role in atherogenesis. The in vivo effects of hyperinsulinemia on endothelial function of large conduit arteries are unknown. Methods and results Twenty-five healthy subjects were enrolled for study. In study A (n=9), subjects underwent both a time-control saline study and a euglycemic low-dose insulin (insulin approximately 110 pmol/L) clamp for 6 hours. Study B (n=5) was identical to study A except that the euglycemic clamp was performed at high physiological insulin concentrations (approximately 440 pmol/L). In study C (n=7), subjects underwent two 4-hour euglycemic insulin (approximately 110 pmol/L) clamps with and without the concomitant infusion of an antioxidant (vitamin C). In study D (n=4), two saline time-control studies were performed with and without the concomitant infusion of vitamin C. In all studies, both at baseline and throughout the experimental period, endothelium-dependent (flow-mediated) and endothelium-independent (nitroglycerin-induced) vasodilation was assessed in femoral and brachial arteries by echo Doppler. Both low (study A) and high physiological (study B) hyperinsulinemia abolished endothelium-dependent vasodilation, whereas endothelium-independent vasodilation was unaffected. Vitamin C fully restored insulin-impaired endothelial function without affecting endothelium-independent vasodilation (study C). Vitami…
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Chronic hyperinsulinemia can cause downregulation of the insulin receptor, thus reducing SI, and may contribute to endothelial dysfunction and atherosclerosis.
“Chronic hyperinsulinemia can cause downregulation of the insulin receptor, thus reducing SI, and may contribute to endothelial dysfunction and atherosclerosis (32).”
From Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With <i>MTNR1B</i> Diabetes Risk Variant (2026) · cites this paper as [32]
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- Authors
- Arcaro, G., Cretti, A., Balzano, S., Lechi, A., Muggeo, M., Bonora, E., & Bonadonna, R. C.
- Affiliations
- University of Verona (IT)
- Venue
- Circulation
- Published
- 2002-02-05
- Volume
- 105
- Issue
- 5
- Pages
- 576-582
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1995800794
- Cited by
- 407
- References
- 2
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 8 · 2023: 8 · 2022: 11 · 2021: 12 · 2020: 5 · 2019: 13 · 2018: 17 · 2017: 13 · 2016: 22 · 2015: 15 · 2014: 15 · 2013: 20 · 2012: 27
- FWCI
- 15.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- hyperinsulinemia, insulin resistance, endothelial dysfunction, endothelium-dependent vasodilation, flow-mediated dilation, nitroglycerin-induced vasodilation, vitamin C, antioxidants, oxidative stress, atherosclerosis, conduit arteries, hyperinsulinemic-euglycemic clamp
- MeSH terms
- Adult, Antioxidants, Ascorbic Acid, Brachial Artery, Dose-Response Relationship, Drug, Endothelium, Vascular, Female, Femoral Artery, Humans, Hyperinsulinism, Insulin, Male, Regional Blood Flow, Sodium Chloride, Vascular Patency, Vasodilation, Vasodilator Agents, Glucose Clamp Technique, Ultrasonography, Doppler, Metabolic Syndrome
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