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.