Gisele Lopes

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

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.

Responsiveness of Glycogen Catabolism to Adrenergic Agonists During Insulin-Induced Hypoglycemia in Rat Livers

1. Insulin-induced hypoglycemia (IIH) promoted decreased responsiveness of hepatic glycogen catabolism to phenylephrine and isoproterenol, but not to glucagon and cyanide. 2. In addition, glycogen phosphorylase activity and glycogen levels were not affected by IIH. 3. It was concluded that hypoglycemia promoted changes in hepatic responsiveness to adrenergic agonists. 4. However, the ability of the liver to mobilize glycogen was not influenced by hypoglycemia.

Time sequence of changes in the responsiveness of glycogen breakdown to adrenergic agonists in perfused liver of rats with insulin-induced hypoglycemia

The time-course changes of the responsiveness of glycogen breakdown to alpha- and ss-adrenergic agonists during insulin-induced hypoglycemia (IIH) were investigated. Blood glucose levels were decreased prior to the alteration in the hepatic responsiveness to adrenergic agonists. The activation of hepatic glucose production and glycogenolysis by phenylephrine (2 microM) and isoproterenol (20 microM) was decreased in IIH. The changes in the responsiveness of glycogen catabolism were first observed for isoproterenol and later for phenylephrine. Hepatic ss-adrenergic receptors showed a higher degree of adrenergic desensitization than did alpha-receptors. Liver glycogen synthase activity, glycogen content and the catabolic effect of dibutyryl cyclic AMP (the ss-receptor second messenger) were not affected by IIH.

Effect of a meal feeding schedule on hepatic glycogen synthesis and gluconeogenesis in rats.

We investigated the effect of a meal feeding schedule (MFS) on food intake, hepatic glycogen synthesis, hepatic capacity to produce glucose and glycemia in rats. The MFS comprised free access to food for a 2-hour period daily at a fixed mealtime (8.00-10.00 a.m.) for 13 days. The control group was composed of rats with free access to food from day 1 to 12, which were then starved for 22 h, refed with a single meal at 8.00-10.00 a.m. and starved again for another 22 h. All experiments were performed at the meal time (i.e. 8.00 a.m.). The MFS group exhibited increased food intake and higher glycogen synthase activity. Since gluconeogenesis from L-glutamine or L-alanine was not affected by MFS, we conclude that the increased food intake and higher glycogen synthase activity contributed to the better glucose maintenance showed by MFS rats at the fixed meal time.