Chronic leptin administration increases insulin-stimulated skeletal muscle glucose uptake and transport

Leptin, the product of the ob gene, has been shown to reduce fat mass, food intake, hyperglycemia, and hyperinsulinemia and to increase whole-body glucose disposal. However, it is unknown if leptin improves insulin action in skeletal muscle. Therefore, the purpose of this investigation was to determine if chronic leptin administration increases insulin-stimulated skeletal muscle glucose uptake and transport. Sixty-nine female Sprague-Dawley rats (240 to 250 g) were randomly assigned to one of three groups: (1) control, (2) pair-fed, and (3) leptin. All animals were subcutaneously implanted with miniosmotic pumps that delivered 0.5 mg leptin/kg/d to the leptin animals and vehicle to the control and pair-fed animals for 14 days. Following this 14-day period, all animals were subjected to hindlimb perfusion to determine the rates of skeletal muscle glucose uptake and 3- O-methyl- d-glucose (3-MG) transport under basal, submaximal (500 μU/mL), and maximal (10,000 μU/mL) insulin concentrations. Chronic leptin treatment significantly increased ( P < .05) the rate of glucose uptake across the hindlimb by 27%, 32%, and 47% under basal, submaximal, and maximal insulin, respectively, compared with the control and pair-fed condition. However, when the submaximal rate of glucose uptake was expressed as a percentage of maximal insulin-stimulated glucose uptake, no differences existed among the groups, indicating that leptin treatment does not increase insulin sensitivity. Rates of 3-MG transport in the soleus, plantaris, and white and red portions of the gastrocnemius (WG and RG) were significantly increased ( P < .05) in leptin animals under all perfusion conditions. 3-MG transport was not different between control and pair-fed animals. Collectively, these findings suggest that improvements in insulin-stimulated skeletal muscle glucose uptake and transport following chronic leptin treatment result from increased insulin responsiveness.