Abstract
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.
Lingua originale | English |
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pagine (da-a) | E947-E947-52 |
Rivista | ENDOCRINOLOGY AND METABOLISM |
Volume | 299 |
DOI | |
Stato di pubblicazione | Pubblicato - 2010 |
Keywords
- Acetylcholine
- Analysis of Variance
- Ascorbic Acid
- Chromatography, High Pressure Liquid
- Dose-Response Relationship, Drug
- Enzyme-Linked Immunosorbent Assay
- Female
- Forearm
- Glutathione
- Humans
- Hyperinsulinism
- Insulin
- Interleukin-6
- Male
- Metabolic Syndrome X
- Nitroprusside
- Obesity
- Regional Blood Flow
- Tumor Necrosis Factor-alpha
- Vasodilation
- Vasodilator Agents
- Verapamil