Physiological insulinemia acutely modulates plasma leptin

Whether insulin acutely regulates plasma leptin in humans is controversial. We examined the dosage-response and time-course characteristics of the effect of insulin on leptin in 10 men (age 42 +/- 2 years [mean +/- SE]; BMI 29.3 +/- 2.0 kg/m(2)). Each individual underwent four 9-h euglycemic clamps (insulin at 20, 40, 80, and 400 mU.m(-2).min(-1)) and a control saline infusion. Although plasma glucose and insulin levels remained constant, leptin diminished from 9.1 +/- 3.0 to 5.9 +/- 2.1 ng/ml (P < 0.001) by the end of the control experiment. Conversely, plasma leptin showed a dosage-dependent increase during the insulin infusions that was evident within 30-60 min. The insulin-induced increase in leptin was proportionately lower in obese insulin-resistant men. Free fatty acids (FFAs) decreased during insulin and did not change during saline infusions. ED50 (the dose producing half-maximal effect) for insulin's effect on leptin and FFA was similar (138 +/- 36 vs. 102 +/- 24 pmol/l, respectively; P = 0.11). To further define the role of physiological insulinemia, we compared the effect of a very low dosage insulin infusion (10 mU.m(-2).min(-1)) with that of a control saline infusion in another group of 10 men (mean age 39 +/- 3 years; BMI 27.1 +/- 1.0 kg/m(2)). Plasma leptin remained stable during that insulin infusion, but fell. by 37 +/- 2% in the control experiment. Thus physiological insulinemia can acutely regulate plasma leptin. Insulin could mediate the effect of caloric intake on leptin and could be a determinant of its plasma concentration. Inadequate insulin-induced leptin production in obese and insulin-resistant subjects may contribute to the development or worsening of obesity.