ROLE OF BLOOD-FLOW IN REGULATING INSULIN-STIMULATED GLUCOSE-UPTAKE INHUMANS STUDIES USING BRADYKININ, [O-15]WATER, AND [F-18] FLUORO-DEOXY-GLUCOSE AND POSITRON EMISSION TOMOGRAPHY

Defects in insulin stimulation of blood flow have been suggested to co ntribute to insulin resistance, To directly test whether glucose uptak e can be altered by changing blood flow, we infused bradykinin (27 mu g over 100 min), an endothelium-dependent vasodilator, into the femora l artery of 12 normal subjects (age 25+/-1 yr, body mass index 22+/-1 kg/m(2)) after an overnight fast (n = 5) and during normoglycemic hype rinsulinemic (n = 7) conditions (serum insulin 465+/-11 pmol/liter, 0- 100 min). Blood flow was measured simultaneously in both femoral regio ns using [O-15]-labeled water ([O-15]H2O) and positron emission tomogr aphy (PET), before and during (50 min) the bradykinin infusion, Glucos e uptake was measured immediately after the blood flow measurement sim ultaneously in both femoral regions using [F-18]-fluoro-deoxy-glucose ([F-15]FDG) and PET, During hyperinsulinemia, muscle blood flow was 58 % higher in the bradykinin-infused (38+/-9 ml/kg muscle . min) than in the control leg (24+/-5, P < 0.01), Femoral muscle glucose uptake was identical in both legs (60.6+/-9.5 vs. 58.7+/-9.0 mu mol/kg . min, br adykinin-infused vs, control leg, NS). Glucose extraction by skeletal muscle was 44% higher in the control (2.6+/-0.2 mmol/liter) than the b radykinin-infused leg (1.8+/-0.2 mmol/liter, P < 0.01), When bradykini n was infused in the basal state, flow was 98% higher in the bradykini n-infused (58+/-12 ml/kg muscle . min) than the control leg (28+/-6 ml /kg muscle . min, P < 0.01) but rates of muscle glucose uptake were id entical in both legs (10.1+/-0.9 vs, 10.6+/-0.8 mu mol/kg . min), We c onclude that bradykinin increases skeletal muscle blood flow but not m uscle glucose uptake in vivo, These data provide direct evidence again st the hypothesis that blood flow is an independent regulator of insul in-stimulated glucose uptake in humans.