Involvement of bradykinin and nitric oxide in leptin-mediated glucose uptake in skeletal muscle

Regulation of glucose metabolism in peripheral tissues by leptin has been h ighlighted recently, although its mechanism is unclear. In this study, we p ostulated that bradykinin and nitric oxide (NO) are involved in the effect of leptin-mediated glucose uptake in peripheral tissues and examined these possibilities. Injection of leptin (200 pg/ mouse) into the ventromedial hy pothalamus-enhanced glucose uptake in skeletal muscle and brown adipose tis sue, but not in white adipose tissue. Treatment with Hoe140 (0.1 mg/kg), br adykinin B2 receptor antagonist, or L-NAME (N-G -nitro-L-arginine methyl es ter) (30 mg/kg), nitric oxide synthase inhibitor, did not influence the bas al level of glucose uptake in skeletal muscle and the adipose tissue, where as Hoe140 and L-NAME inhibited leptin-mediated glucose uptake in skeletal m uscles, but had no effect in adipose tissue. However, Hoe140 and L-NAME did not inhibit insulin (1.0 U/kg)-mediated glucose uptake in all tissues exam ined. Taken together, these results suggest that leptin enhances bradykinin and/or the NO system, which contributes at least partially to the enhanced glucose uptake in skeletal muscles.