ACUTE AND CHRONIC EFFECT OF INSULIN ON LEPTIN PRODUCTION IN HUMANS - STUDIES IN-VIVO AND IN-VITRO

This study was undertaken to investigate the changes in obesity (OB) g ene expression and production of leptin in response to insulin in vitr o and in vivo under euglycemic and hyperglycemic conditions in humans. Three protocols were used: 1) euglycemic clamp with insulin infusion rates at 40, 120, 300, and 1,200 mU . m(-2) . min(-1) carried out for up to 5 h performed in 16 normal lean individuals, 30 obese individual s, and 31 patients with NIDDM; 2) 64- to 72-h hyperglycemic (glucose 1 2.6 mmol/l) clamp performed on 5 lean individuals; 3) long-term (96-h) primary culture of isolated abdominal adipocytes in the presence and absence of 100 nmol/l insulin. Short-term hyperinsulinemia in the rang e of 80 to > 10,000 mu U/ml had no effect on circulating levels of lep tin. During the prolonged hyperglycemic clamp, a rise in leptin was ob served during the last 24 h of the study (P < 0.001). In the presence of insulin in vitro, OB gene expression increased at 72 h (P < 0.01), followed by an increase in leptin released to the medium (P < 0.001). In summary, insulin does not stimulate leptin production acutely; howe ver, a long-term effect of insulin on leptin production could be demon strated both in vivo and in vitro. These data suggest that insulin reg ulates OB gene expression and leptin production indirectly, probably t hrough its trophic effect on adipocytes.