EFFECT OF HYPERINSULINEMIA ON PLASMA LEPTIN CONCENTRATIONS AND FOOD-INTAKE IN RATS

We investigated the dose- and time-dependent effect of insulin infusio n on peripheral and portal plasma leptin concentrations in normal rats . Three groups were studied: group I: euglycemic (6 mmol/l) insulin (6 mU.kg(-1).min(-1)) clamps for 0, 2, 4, 12, and 24 h; group II: euglyc emic insulin (l8 mU.kg(-1).min(-1)) clamp for 2 h; and group III: eugl ycemic insulin (3 mU.kg(-1).min(-1)) clamp for 7 days. In group III, f ood intake was quantified during days 1-7. After an overnight fast, pe ripheral and portal plasma leptin levels were identical (1.5 +/- 0.2 a nd 1.6 +/- (2.0 +/- 0.2 ng/ml), 12 h (2.2 +/- 0.4 ng/ml), and 24 h (2. 7 +/- 0.6 ng/ml; all P < 0.05) of insulin infusion, a progressive time -related increase in plasma leptin concentration was observed; portal vein leptin levels rose in parallel and were similar to peripheral lev els. When insulin (18 mU.kg(-1).min(-1)) was infused for 2 h, plasma l eptin levels increased to 3.0 +/- 0.3 ng/ml (P < 0.01). Seven days of constant insulin infusion (3 mU.kg(-1).min(-1)) resulted in a progress ive increase in fasting plasma leptin and a parallel decrease in food intake. A mean increase in plasma leptin concentration of 1 ng/ml duri ng the 7-day insulin infusion period was associated with a mean decrea se in food intake of 2.5 g/day (multivariate ANOVA, P < 0.05). We conc lude that the insulin-induced rise in peripheral and portal vein lepti n levels is similar and both dose and time dependent. The inverse rela tionship between plasma leptin concentration and food intake during pr olonged hyperinsulinemia, but not during short-term hyperinsulinemia, supports the role of leptin in long-term food consumption.