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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:320.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Glargine and Regular Human Insulin Similarly Acutely Enhance Endothelium-Dependent Vasodilatation in Normal Subjects

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

From the University of Helsinki, Department of Medicine, Division of Diabetes, Helsinki, Finland.

Correspondence to Dr Jukka Westerbacka, Department of Medicine, Division of Diabetes, University of Helsinki, P.O. Box 340, FIN-00029 HUCH, Helsinki, Finland. E-mail jukka.westerbacka{at}helsinki.fi

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 µg/min) and high (10 µg/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 µg/min) and high (15 µg/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).

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

Key Words: arteries • insulin-like growth factor-1 • vasculature

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