Comparing effects of leptin and insulin on glucose metabolism in skeletal muscle: evidence for an effect of leptin on glucose uptake and decarboxylation

OBJECTIVE: To investigate the effects of leptin and the combination of insulin and leptin on glucose metabolism in incubated rat soleus muscle. ANIMALS: Male lean albino rats (50 - 70 g) of the Wistar strain were used in all experiments. MEASUREMENTS: 2-Deoxy-D-[H-3]-glucose (2-DG) uptake, glycogen synthesis, lactate synthesis, glucose and pyruvate decarboxylation. RESULTS: Leptin (1, 10 and 100 nM), increased 2-Deoxyglucose uptake from 4.07 +/- 0.23 mu mol/h(-1)/g(-1) (basal) to 5.88+/-0.29 mu mol/h(-1)/g(-1) (100 nM) (P < 0.05); however, leptin did not potentiate the effect of either physiological (100 mu U/ml) or supra-physiological (10000 mu U/ml) insulin concentrations on glucose uptake. Glycogen synthesis rose almost 2-fold in the presence of supra-physiological leptin concentrations (100 nM), The combination of insulin and leptin did not present any additional effect on glycogen synthesis beyond that caused by insulin. Compared to the control group, the decarboxylation of [U-C-14] D-glucose increased 75%, 246% and 304% (P < 0.05) in the presence of 1, 10 and 100 nM leptin, respectively. When leptin (100 nM) was combined with insulin in the incubation medium, the (CO2)-C-14 production rose almost 4-fold (397%) (P < 0.05) and more than 5-fold (527%) (P < 0.05) for the 100 mu U/ml and 10000 mu U/ml insulin concentrations, respectively. In the presence of leptin (100 nM), the decarboxylation of [1-C-14]- and [2-C-14]-pyruvate in incubated muscles rose 89% and 49%, respectively, indicating that both pyruvate dehydrogenase and Krebs cycle are activated by leptin, CONCLUSION: These data demonstrate that, in soleus muscle, leptin per se exerts a direct and acute insulin-like effect, stimulating glucose uptake, glycogen synthesis, lactate formation and glucose oxidation.