Effects of prolonged hyperinsulinemia on serum leptin in normal human subjects

Abstract

We have studied the effect of prolonged hyperinsulinemia and hyperglycemia on serum leptin levels in young non-obese males during 72-h euglycemic-hyperinsulinemic and hyperglycemic (~ 8.5 and 12.6 mM) clamps. Hyperinsulinemia increased serum leptin concentrations (by RIA) dose- dependently. An increase in serum insulin concentration of > 200 pM for > 24 h was needed to significantly increase serum leptin. An increase of ~ 800 pM increased serum leptin by ~ 70% over 72 h. Changes in plasma glucose concentrations (from ~ 5.0 to ~ 12.6 mM) or changes in plasma FFA concentrations (from < 100 to > 1,000 μM) had no effect on serum leptin. Serum leptin concentrations changed with circadian rhythmicity. The cycle length was ~ 24 h, and the cycle amplitude (peak to trough) was ~ 50%. The circadian leptin cycles and the circadian cycles of total body insulin sensitivity (i.e., GIR, the glucose infusion rates needed to maintain euglycemia during hyperinsulinemic clamping) changed in a mirror image fashion. Moreover, GIR decreased between Days 2 and 3 (from 11.4 ± 0.2 to 9.8 ± 0.2 mg/kg min, P< 0.05) when mean 24-h leptin levels reached a peak. In summary, we found (a) that 72 h of hyperinsulinemia increased serum leptin levels dose-dependently; (b) that hyperglycemia or high plasma FFA levels did not affect leptin release; (c) that leptin was released with circadian rhythmicity, and (d) that 24-h leptin cycles correlated inversely with 24-h cycles of insulin sensitivity. We speculate that the close positive correlation between body fat and leptin is mediated, at least in part, by insulin.