Acute effects of leptin on glucose metabolism of in situ rat perfused livers and isolated hepatocytes

OBJECTIVE: To investigate whether leptin interferes directly with glycogeno lysis and gluconeogenesis in isolated rat hepatocytes and also in in situ r at perfused livers. ANIMALS: Male albino rats (200-250 g) were used in all experiments. MEASUREMENTS: D-glucose, L-lactate and pyruvate production. RESULTS: In the present study, no differences were found for the rates of g lycolysis, as expressed by the areas under the curves, among control (24.2/-5.0 mmol/g), leptin (32.0+/-4.5 mmol/g), glucagon (24.7+/-3.0 mmol/g), an d the leptin + glucagon (23.8+/-3.4 mmol/g) groups. No difference was found for the rates of glycogenolysis between the control and the leptin perfuse d livers (15.2+/-3.9 and 15.0+/-3.2 mmol/g, respectively). In the presence of glucagon, the areas under the curves for the rate of glycogenolysis rose to 108.6+/-3.8 mmol/g. When leptin was combined with glucagon, the area un der the curve for glycogenolysis was 43.7+/-4.3 mmol/g. In fact, leptin cau sed a reduction of almost 60% (P<0.001) in the rate of glucagon-stimulated glycogenolysis. Under basal conditions, the addition of leptin (100 ng/ml) to the incubation medium did not elicit any alteration in glucose productio n by isolated hepatocytes. However, in the presence of leptin, the producti on of glucose from glycerol (2 mM), L-lactate (2 mM). L-alanine (5 mM) and L-glutamine (5 mM) by the isolated hepatocytes was significantly reduced (3 0%, 30%, 23% and 25%, respectively). The rate of glucose production (glycog enolysis) by isolated hepatocytes was not different between the control and the leptin incubated groups (445.0+/-91.0 and 428.0+/-72.0 nmol/10(6) cell s/h, respectively). CONCLUSION: We conclude that leptin per se does not directly affect either liver glycolysis or its glucose production, but a physiological leptin conc entration is capable of acutely inducing a direct marked reduction on the r ate of glucagon-stimulated glucose production in in situ rat perfused liver . Leptin is also capable of reducing glucose production from different gluc oneogenic precursors in isolated hepatocytes.