The Interaction of Blood Flow, Insulin, and Bradykinin in Regulating Glucose Uptake in Lower-Body Adipose Tissue in Lean and Obese Subjects

Context: Impaired adipose tissue (AT) blood flow hasbeenimplicated in the pathogenesis of insulin resistance in obesity. Insulin and bradykinin are meal-stimulated promoters of AT blood flow and glucose metabolism. Objective: We tested whether blood flow regulates glucose metabolism in AT, insulin and brady-kinin exert additive effects on AT blood flow and metabolism, and any of these actions explains the insulin resistance observed in obese individuals. Design: Perfusionandglucose metabolism in the ATof the thighswerestudied by positron emission tomography and H2 15O (flow tracer) and 18F-2-fluoro-2-deoxyglucose. Study I included five subjects in whom positron emission tomography imaging was performed in the fasting state during intraarterial infusion of bradykinin in the left leg; the right leg served as a control. Study II included seven lean and eight obese subjects in whom the imaging protocol was performed during euglycemic hyperinsulinemia. Results: Bradykinin alone doubled fasting AT blood flow without modifying glucose uptake. Hyperinsulinemia increased AT blood flow (P<=0.05) similarly in leanandobese individuals. In the lean group, bradykinin increased insulin-mediated AT glucose uptake from 8.6 ± 1.6 to 12.3 ± 2.4 ?mol/min · kg (P = 0.038). In the obese group, AT glucose uptake was impaired (5.0 ± 1.0 ?mol/min · kg, P = 0.05 vs. the lean group), and bradykinin did not exert any metabolic action (6.0 ± 0.8 ?mol/min · kg, P = 0.01 vs. the lean group). Conclusion: AT blood flow is not an independent regulator of AT glucose metabolism. Insulin is a potent stimulator of AT blood flow, and bradykinin potentiates the hemodynamic and metabolic actions of insulin in lean but not in obese individuals.