Effects of insulin and glucocorticoids on the leptin system are mediated through free leptin

OBJECTIVE Insulin and glucocorticoids are known to increase total leptin le vels. However, the effects of insulin and glucocorticoids on the components of the leptin system - free leptin (FL), hound leptin (BL) and soluble lep tin receptor (SR)- have not been elucidated. The aim of this study was to d etermine if there is a differential effect of insulin and glucocorticoids o n the leptin system. MATERIAL AND METHODS In the first of two studies (study 1), we measured fre e leptin (FL), bound leptin (BL), a soluble leptin receptor (SR) and insuli n, by specific RIA methods, in six healthy subjects on a control day, and s ubsequently during a hyperinsulinaemic euglycaemic clamp study. In the seco nd study (study 2) we measured the same parameters in six healthy subjects, before (day 1) and during administration of dexamethasone over 3 consecuti ve days. RESULTS In study 1, on the control day FL levels rose over the 16 h monitor ing period (P = 0.051) and SR levels declined (P < 0.001), but there was no change of BL levels. Even after accounting for diurnal variation, FL level s increased even more substantially over 12 h of insulin infusion than obse rved on the control day (P < 0.001). In study 2, mean FL concentration doub led from day 1 to day 2 (P = 0.01) and remained elevated subsequently, in c ontrast to FL. BL and SR revels remained unchanged during the study. Fastin g insulin levels (pmol/l) increased from day 1 to day 2, but this rise only approached significance on day 4 (P = 0.05). CONCLUSION We conclude that Insulin end dexamethasone increase free leptin levels, but do not change the concentrations of bound leptin and soluble le ptin receptor. Furthermore, the dexamethasone-induced rise in leptin levels is (at least partially) Independent of the effects of glucocorticoid-induc ed hyperinsulinaemia.