Insulin-Mediated Vasodilation and Glucose Uptake Are Functionally Linked in Humans

Abstract

Abstract —Intra-arterial infusion of insulin in physiological doses causes forearm vasodilation which is augmented by co-infusion of d -glucose, leading us to speculate that local insulin-mediated vasodilation may depend on insulin-mediated glucose uptake. We have examined the relationship between whole-body insulin sensitivity and forearm vasodilation in response to local infusion of insulin/glucose, thus avoiding any confounding effects of sympathetic stimulation on peripheral blood flow. Eighteen healthy, normotensive male volunteers (age, 26±5.4 years) attended on two separate occasions for measurement of: (1) whole-body insulin sensitivity with use of the hyperinsulinemic euglycemic clamp; (2) forearm vasodilation in response to an intra-arterial infusion of insulin/glucose with use of bilateral venous occlusion plethysmography. Insulin-mediated glucose uptake (M) for the group (mean±SD) was 10.0±2.2 mg · kg −1 · min −1 , and the percentage change in forearm blood flow ratio (%FBFR) for the group (median, interquartile range) was 28.2% (13.6, 48.6). In univariate analysis, M was significantly correlated with %FBFR ( r s =0.60, P <0.05), but not with body mass index (BMI) ( r s =−0.42), age ( r =−0.39) or mean arterial pressure ( r =0.13). In multiple regression analysis, %FBFR remained a significant independent predictor of M ( R 2 (adj)=0.48, t =3.23, P <0.01) in a model involving BMI, age, and blood pressure. These data support the concept of a significant functional relationship between insulin’s metabolic and vascular actions, possibly at an endothelial level.