EFFECTS OF HYPERINSULINEMIA AND HYPOGLYCEMIA ON CIRCULATING LEPTIN LEVELS IN HEALTHY LEAN MALES

Current knowledge of the regulatory mechanisms of leptin synthesis and release is limited. To elucidate the role of short-term hyperinsulina emia and hypoglycaemia on circulating levels of leptin, 7 healthy lean men underwent a 360-min hyperinsulinaemic (insulin infusion rate: 1.5 mU/kg/min) clamp in two conditions:(i) during 360 min of euglycaemia and (ii) during 120 min of euglycaemia followed by 240 min of graded h ypoglycaemia (nadir 2.9 +/- 0.1 mmol/l). During hyperinsulinaemic eugl ycaemia, serum leptin levels were initially stable and then rose gradu ally after 180 min to a peak value of 147 +/- 7 % of baseline (ANOVA, p < 0.01). During the hypoglycaemic clamp, the leptin profile differed from that of euglycaemic conditions (p < 0.01) since the increase was postponed and reduced. In both clamp studies,leptin dynamics contrast ed with the changes in a control study performed in 7 other men whose serum leptin fell significantly (p < 0.05) to 77 +/- 4 % of baseline v alues during a 360-min fast (following overnight fasting). It is concl uded that hyperinsulinaemia for more than 3 h increases circulating le vels of leptin in lean males, whereas hyperinsulinaemia with concomita nt hypoglycaemia leads to transient suppression. The exact nature of t he underlying mechanisms, e.g, changes in levels of insulin, glucose, various substrates, glucose turnover and/or counterregulatory hormones , remains to be determined.