Effects of acute hyperinsulinemia on plasma leptin concentrations in insulin-sensitive and insulin-resistant Pima Indians.

Leptin, a recently discovered protein produced in adipocytes, may be important in the regulation of body energy stores. In humans, leptin is present in the circulation in direct proportion to the amount of body fat. In rodents, insulin seems to regulate the production of leptin, but there is only limited evidence that this occurs in humans. We, therefore, measured plasma leptin concentrations in 13 insulin-sensitive and 13 insulin-resistant Pima Indians at baseline, at the end of 100 min of physiologic hyperinsulinemia (mean plasma insulin = 563 pmol/L) and after a further 100 min of supraphysiologic hyperinsulinemia (mean plasma insulin = 11,910 pmol/L), during a 2-step hyperinsulinemic-euglycemic glucose clamp. At baseline, plasma leptin concentrations were directly related to percent body fat, determined by hydrodensitometry (r = 0.85, P < 0.0001). After adjusting for percent body fat, there were no differences in fasting plasma leptin concentrations between insulin-sensitive and insulin-resistant subjects. Plasma leptin concentrations did not change in response to insulin in either the insulin-sensitive or insulin-resistant subjects. These results suggest that insulin does not acutely regulate plasma leptin concentrations in humans.