VASODILATOR RESPONSE TO SYSTEMIC BUT NOT TO LOCAL HYPERINSULINEMIA INTHE HUMAN FOREARM

Insulin-mediated vasodilation has been proposed as an important determ inant of whole-body insulin-stimulated glucose disposal. However, it i s not clear whether the vasodilator effect of insulin results from a d irect action of the hormone or whether alternative mechanisms are invo lved. To better characterize the mechanism of insulin-mediated vasorel axation, we compared forearm blood flow (FBF) responses to local (intr a-arterial) and systemic (intravenous, euglycemic clamp) hyperinsuline mia in 10 healthy lean subjects using venous occlusion plethysmography . In addition, we assessed the effect of nitric oxide (NO) synthase in hibition by N-G-monomethyl-L-arginine (L-NMMA) on the vasodilator and metabolic responses to hyperinsulinemia. Similar forearm concentration s of insulin were achieved during local and systemic infusion (231+/-3 9 versus 265+/-22 mu U/mL; P=0.54). Of note, FBF did not change signif icantly in response to local hyperinsulinemia (from 2.6+/-0.3 to 2.4+/ -0.3 mt . min(-1) . dL(-1); P=0.50). In contrast, systemic hyperinsuli nemia caused a 52% increase in FBF (from 2.5+/-0.2 to 3.8+/-0.5 mL . m in(-1) . dL(-1); P<0.004), which was reversed by L-NMMA (FBF decreased from 3.8+/-0.5 to 2.3+/-0.2 mL . min(-1) . dL(-1); P=0.004). We concl ude that systemic, but not local, hyperinsulinemia induces vasodilatio n in the forearm. Our findings suggest that insulin-mediated vasodilat ion is not due solely to a direct stimulatory effect of insulin but in volves additional mechanisms activated only during systemic hyperinsul inemia.