Document Detail


Generalized impairment of vasodilator reactivity during hyperinsulinemia in patients with obesity-related metabolic syndrome.
MedLine Citation:
PMID:  20923961     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Defective insulin-dependent vasodilation might contribute importantly to metabolic and vascular abnormalities of the metabolic syndrome (MetS). However, despite extensive investigation, the precise mechanisms involved in insulin's vasoactive effects have not been fully elucidated. Therefore, this study sought to better characterize insulin's physiological actions on vascular reactivity and their potential derangement in the MetS. Forearm blood flow responses to graded doses of acetylcholine, sodium nitroprusside, and verapamil were assessed by strain-gauge plethysmography in patients with obesity-related MetS (n = 20) and in matched controls (n = 18) before and after intra-arterial infusion of insulin (0.2 mU·kg(-1)·min(-1)). Possible involvement of increased oxidative stress in the impaired insulin-stimulated vasodilator responsiveness of patients with MetS (n = 12) was also investigated using vitamin C (25 mg/min). In control subjects, significant potentiation of the vasodilator responses to acetylcholine, nitroprusside, and verapamil was observed after insulin infusion (all P < 0.05). However, no significant change in vasodilator reactivity to either of these drugs was observed following hyperinsulinemia in patients with MetS (all P > 0.05). Interestingly, administration of vitamin C to patients with MetS during hyperinsulinemia significantly enhanced the vasodilator responsiveness to acetylcholine, nitroprusside, and verapamil (all P < 0.05 vs. hyperinsulinemia alone). In conclusion, insulin exerts a generalized facilitatory action on vasodilator reactivity, and this effect is impaired in patients with MetS likely because of increased oxidative stress. Given the importance of vasodilator reactivity in affecting glucose disposal and vascular homeostasis, this defect may then contribute to the development of metabolic and vascular complications in insulin-resistant states.
Authors:
Francesca Schinzari; Manfredi Tesauro; Valentina Rovella; Angelica Galli; Nadia Mores; Ottavia Porzio; Davide Lauro; Carmine Cardillo
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-05
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  299     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-30     Completed Date:  2010-12-28     Revised Date:  2011-08-12    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E947-52     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, University of Tor Vergata, Rome, Italy.
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / pharmacology
Analysis of Variance
Ascorbic Acid / pharmacology
Chromatography, High Pressure Liquid
Dose-Response Relationship, Drug
Enzyme-Linked Immunosorbent Assay
Female
Forearm / blood supply
Glutathione / blood
Humans
Hyperinsulinism / complications,  metabolism,  physiopathology*
Insulin / blood
Interleukin-6 / blood
Male
Metabolic Syndrome X / complications,  metabolism,  physiopathology*
Nitroprusside / pharmacology
Obesity / complications,  metabolism,  physiopathology*
Regional Blood Flow / physiology
Tumor Necrosis Factor-alpha / blood
Vasodilation / drug effects,  physiology*
Vasodilator Agents / pharmacology
Verapamil / pharmacology
Chemical
Reg. No./Substance:
0/Interleukin-6; 0/Tumor Necrosis Factor-alpha; 0/Vasodilator Agents; 11061-68-0/Insulin; 15078-28-1/Nitroprusside; 50-81-7/Ascorbic Acid; 51-84-3/Acetylcholine; 52-53-9/Verapamil; 70-18-8/Glutathione
Comments/Corrections
Comment In:
Am J Physiol Endocrinol Metab. 2011 Jul;301(1):E242-3; author reply E244   [PMID:  21705628 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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