Insulin impairs endothelium-dependent vasodilation independent of insulin sensitivity or lipid profile
Insulin impairs endothelium-dependent vasodilation independent of insulin sensitivity or lipid profile
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DOI：
10.1152/ajpheart.00539.2003
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发表时间：
2004-01-01
影响因子：
4.8
通讯作者：
Panza, JA
中科院分区：
文献类型：
--
作者：
Campia, U;Sullivan, G;Panza, JA
胰岛素抵抗是动脉粥样硬化的危险因素，与高胰岛素血症、血脂异常和高血压有关。高胰岛素血症是否影响血管功能而与胰岛素抵抗或其他代谢危险因素无关尚不清楚。本研究旨在评估高胰岛素血症对具有一系列胰岛素敏感性和血脂谱的受试者内皮功能的影响。在 25 名血糖正常、血压正常的受试者中，通过高分辨率超声在高胰岛素血症（正常血糖钳夹）之前和期间研究了肱动脉的内皮依赖性（血流介导的扩张，FMD）和非依赖性（硝酸甘油）反应。根据敏感性指数值将参与者分为胰岛素敏感亚组和胰岛素抵抗亚组（临界值为 8），并根据总胆固醇水平分为正常胆固醇和高胆固醇亚组，临界值为 5.2 mmol/l（200 mg/dl）。在整个人群中，与基线相比，高胰岛素血症期间的 FMD 较低（2.3 +/- 0.6% vs. 6 +/- 0.6%；P < 0.001）。与胰岛素敏感亚组相比，胰岛素抵抗亚组的静息 FMD 较低（4.2 +/- 0.9% 对比 7.4 +/- 0.8%；P = 0.014），高胆固醇受试者的静息 FMD 低于正常胆固醇受试者（4.4 +/- 0.7% 对比 8 +/- 0.7%；P = 0.002）。高胰岛素血症降低了胰岛素敏感性（从 7.4 +/- 0.8% 到 3.6 +/- 0.4%；P < 0.001）和胰岛素抵抗（从 4.2% 到 1.22%；P = 0.012）亚组以及正常胆固醇（从 8 +/- 0.7% 到 3.9 +/- 0.4%；P < 0.012）的 FMD。 0.001）和高胆固醇（从 4.4 +/- 0.7% 到 1.1 +/- 0.8%；P = 0.01）参与者。急性高胰岛素血症损害导管内皮功能，与胰岛素敏感性和脂质分布无关。胰岛素可能引发内皮功能障碍并促进动脉粥样硬化。
Insulin resistance is a risk factor for atherosclerosis and is associated with hyperinsulinemia, abnormal lipid profile, and hypertension. Whether hyperinsulinemia affects vascular function independent of insulin resistance or other metabolic risk factors is unknown. This investigation aimed to assess the effects of hyperinsulinemia on endothelial function in subjects with a spectrum of insulin sensitivity and lipid profile. Endothelium- dependent ( flow- mediated dilation, FMD) and - independent ( nitroglycerin) responses of the brachial artery were studied by high- resolution ultrasound before and during hyperinsulinemia ( euglycemic clamp) in 25 normoglycemic, normotensive subjects. Participants were divided into an insulin- sensitive and an insulin-resistant subgroup based on their sensitivity index values, with a cutoff of 8, and into a normal- cholesterol and a high- cholesterol subgroup based on their total cholesterol levels, with a cutoff of 5.2 mmol/ l ( 200 mg/ dl). In the whole population, FMD was lower during hyperinsulinemia compared with baseline ( 2.3 +/- 0.6% vs. 6 +/- 0.6%; P < 0.001). Resting FMD was lower in the insulin- resistant subgroup compared with the insulin- sensitive subgroup ( 4.2 +/- 0.9% vs. 7.4 +/- 0.8%; P = 0.014) and in the high- cholesterol subjects compared with the normal- cholesterol subjects ( 4.4 +/- 0.7% vs. 8 +/- 0.7%; P = 0.002). Hyperinsulinemia decreased FMD in both the insulin- sensitive ( from 7.4 +/- 0.8% to 3.6 +/- 0.4%; P < 0.001) and insulin- resistant ( from 4.2% to 1.22%; P = 0.012) subgroups and in both the normal- cholesterol ( from 8 +/- 0.7% to 3.9 +/- 0.4%; P < 0.001) and high- cholesterol ( from 4.4 +/- 0.7% to 1.1 +/- 0.8%; P = 0.01) participants. Acute hyperinsulinemia impairs conduit vessel endothelial function independent of insulin sensitivity and lipid profile. Insulin may trigger endothelial dysfunction and promote atherosclerosis.