INSULIN-MEDIATED SKELETAL-MUSCLE VASODILATION CONTRIBUTES TO BOTH INSULIN SENSITIVITY AND RESPONSIVENESS IN LEAN HUMANS

Whether insulin-mediated vasodilation is important in determining insu lin's overall action to stimulate glucose uptake is unknown To this en d, we measured leg glucose uptake during euglycemic hyperinsulinemic c lamps performed at two insulin doses (40 mU/m(2) per min, n = 6 and 12 0 mU/m(2) per min, n = 15) alone and during a superimposed intrafemora l artery infusion of N-G-monomethyl-L-arginine (L-NMMA) designed to bl unt insulin-mediated vasodilation, During the higher dose study, hyper insulinema resulted in about a twofold rise in basal leg blood dow fro m 0.24+/-0.02 to 0.45+/-0.05 liter/min, P < 0.0001. L-NMMA infusion re sulted in a net 21% reduction in leg glucose uptake from 114+/-18 mg/m in to 85+/-13 mg/min, P < 0.001. We also found a significant relations hip between the rate of insulin-stimulated whole body glucose uptake a nd the magnitude of dow dependent glucose uptake (r = 0.57, P = 0.02), Data obtained during the lower dose insulin infusion resulted in simi lar findings. In conclusion, in healthy lean subjects, insulin-stimula ted muscle blood how contributes to both insulin responsiveness and in sulin sensitivity, The most insulin-sensitive subjects appear to be th e most reliant on muscle perfusion for insulin action, Insulin-mediate d vasodilation is an important physiological determinant of insulin ac tion.