Obesity/insulin resistance is associated with endothelial dysfunction - Implications for the syndrome of insulin resistance
Obesity/insulin resistance is associated with endothelial dysfunction - Implications for the syndrome of insulin resistance
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DOI：
10.1172/jci118709
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发表时间：
1996-06-01
影响因子：
15.9
通讯作者：
Baron, AD
中科院分区：
文献类型：
--
作者：
Steinberg, HO;Chaker, H;Baron, AD
为了验证肥胖/胰岛素抵抗损害内皮依赖性血管舒张和胰岛素介导的内皮依赖性血管舒张增强的假设，我们研究了瘦胰岛素敏感对照组(C)和肥胖胰岛素抵抗受试者（OB）在生理盐水输注和血糖高胰岛素血症期间，分阶段在股骨动脉内输注氯甲胆碱（MCh）或硝基普钠（SNP）时的腿血流量（LBF）反应。非胰岛素依赖型糖尿病（NIDDM）患者。MCh诱导的LBF增加量在OB和NIDDM组分别比C组低40%和55% （P < 0.05）。正常血糖高胰岛素血症使C组的LBF对MCh的反应增加了50% (P < 0.05)，而OB和NIDDM组则没有。SNP在所有组中引起了相当的LBF增量。回归分析显示，最大LBF变化对MCh的响应与体脂含量呈显著负相关。因此，肥胖/胰岛素抵抗与(a)内皮依赖型血管舒张减弱，但正常的内皮依赖型血管舒张和(b)正糖高胰岛素血症不能增强内皮依赖型血管舒张有关。因此，肥胖/胰岛素抵抗受试者的特点是内皮功能障碍和内皮抵抗胰岛素对内皮依赖性血管舒张增强的作用。这种内皮功能障碍可能会增加肥胖胰岛素抵抗患者动脉粥样硬化的风险。
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 similar to 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 similar to 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.