在正常受试者中，甘精胰岛素和常规人胰岛素同样能急性增强内皮依赖性血管舒张。

Glargine and regular human insulin similarly acutely enhance endothelium-dependent vasodilatation in normal subjects.

作者信息

Westerbacka Jukka, Bergholm Robert, Tiikkainen Mirja, Yki-Järvinen Hannele

机构信息

Department of Medicine, Division of Diabetes, University of Helsinki, P.O. Box 340, FIN-00029 HUCH, Helsinki, Finland.

出版信息

Arterioscler Thromb Vasc Biol. 2004 Feb;24(2):320-4. doi: 10.1161/01.ATV.0000110444.59568.56. Epub 2003 Dec 4.

DOI:10.1161/01.ATV.0000110444.59568.56

PMID:14656737

Abstract

OBJECTIVE

Human insulin enhances the vasodilatory effect of acetylcholine (ACh), an endothelium-dependent vasodilator, in normal subjects. Structural changes in a long-acting insulin analog, insulin glargine, may change its binding properties to insulin receptor and structurally homologous receptors, such as the insulin-like growth factor-1 receptor, and thereby alter its vascular effects. In the present study, we compared effects of glargine and regular human insulin on blood flow responses to endothelium-dependent and endothelium-independent vasoactive agents in vivo in normal subjects.

METHODS AND RESULTS

Ten healthy men (age: 33+/-9 years [mean+/-SD]; BMI: 23+/-2 kg/m2) were studied on two separate occasions in a double-blind, randomized, crossover fashion. In each study, blood flow responses to intrabrachial artery infusions of ACh and SNP were determined during infusion of saline and intravenously maintained normoglycemic hyperinsulinemia. Hyperinsulinemia (120 minutes; infusion rate: 1 mU/kg per minute) was created by infusing either insulin glargine or human regular insulin. Glargine and human regular insulin similarly stimulated whole-body glucose metabolism and suppressed serum free-fatty acid (FFA) concentrations. Endothelium-independent blood flow responses to low (3 microg/min) and high (10 microg/min) doses of SNP were unaffected by insulin glargine (12.2+/-2.6 versus 13.4+/-4.6 and 19.1+/-4.2 versus 19.6+/-5.1 mL/dL per minute, saline versus insulin, low- and high-dose) and regular human insulin (11.2+/-3.4 versus 12.0+/-5.2 and 16.8+/-5.7 versus 18.4+/-7.7 mL/dL per minute, respectively). In contrast, endothelium-dependent blood flow responses to low (7.5 microg/min) and high (15 microg/min) doses of ACh increased significantly and similarly by insulin glargine, 13.9+/-4.8 versus 19.3+/-6.5 mL/dL per minute (saline versus insulin, +39%, P<0.01) for low-dose ACh and 17.3+/-6.3 versus 23.2+/-9.2 mL/dL per minute (+34%; P<0.02) for high-dose ACh, and regular human insulin, 11.5+/-6.0 versus 15.8+/-8.0 mL/dL per minute (+38%; P<0.05) and 14.0+/-7.5 versus 21.1+/-10.4 mL/dL per minute (+51%; P<0.01).

CONCLUSIONS

Insulin glargine and regular human insulin have similar acute stimulatory effects on endothelium-dependent vasodilation in humans.

摘要

目的

在正常受试者中，人胰岛素可增强乙酰胆碱（ACh，一种内皮依赖性血管舒张剂）的血管舒张作用。长效胰岛素类似物甘精胰岛素的结构变化可能会改变其与胰岛素受体及结构同源受体（如胰岛素样生长因子-1受体）的结合特性，从而改变其血管效应。在本研究中，我们比较了甘精胰岛素和常规人胰岛素对正常受试者体内内皮依赖性和非内皮依赖性血管活性药物血流反应的影响。

方法与结果

10名健康男性（年龄：33±9岁[均值±标准差]；体重指数：23±2kg/m²）以双盲、随机、交叉方式在两个不同时间段进行研究。在每项研究中，在输注生理盐水及静脉维持正常血糖高胰岛素血症期间，测定肱动脉内输注ACh和硝普钠（SNP）时的血流反应。通过输注甘精胰岛素或人常规胰岛素产生高胰岛素血症（120分钟；输注速率：1mU/kg每分钟）。甘精胰岛素和人常规胰岛素同样刺激全身葡萄糖代谢并抑制血清游离脂肪酸（FFA）浓度。低剂量（3μg/min）和高剂量（10μg/min）SNP引起的非内皮依赖性血流反应不受甘精胰岛素（生理盐水与胰岛素相比，低剂量时分别为12.2±2.6与13.4±4.6mL/dL每分钟，高剂量时分别为19.1±4.2与19.6±5.1mL/dL每分钟）和常规人胰岛素（分别为11.2±3.4与12.0±5.2mL/dL每分钟，16.8±5.7与18.4±7.7mL/dL每分钟）影响。相比之下，低剂量（7.5μg/min）和高剂量（15μg/min）ACh引起的内皮依赖性血流反应在甘精胰岛素作用下显著且相似地增加，低剂量ACh时为13.9±4.8与19.3±6.5mL/dL每分钟（生理盐水与胰岛素相比，增加39%，P<0.01），高剂量ACh时为17.3±6.3与23.2±9.2mL/dL每分钟（增加34%；P<0.02）；在常规人胰岛素作用下，低剂量ACh时为11.5±6.0与15.8±8.0mL/dL每分钟（增加38%；P<0.05），高剂量ACh时为14.0±7.5与21.1±10.4mL/dL每分钟（增加51%；P<0.01）。