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

Abstract

OBJECTIVE: To investigate whether leptin interferes directly with glycogenolysis and gluconeogenesis in isolated rat hepatocytes and also in in situ rat 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 glycolysis, 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), and 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 perfused 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 under the curve for glycogenolysis was 43.7+4.3 mmol\g. In fact, leptin caused 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 production by isolated hepatocytes. However, in the presence of leptin, the production 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 (30%, 30%, 23% and 25%, respectively). The rate of glucose production (glycogenolysis) by isolated hepatocytes was not different between the control and the leptin incubated groups (445.0±91.0 and 428.0±72.0 nmol\10⁶ cells\h, respectively).

CONCLUSION: We conclude that leptin per se does not directly affect either liver glycolysis or its glucose production, but a physiological leptin concentration is capable of acutely inducing a direct marked reduction on the rate of glucagon-stimulated glucose production in in situ rat perfused liver. Leptin is also capable of reducing glucose production from different gluconeogenic precursors in isolated hepatocytes.