OBJECTIVE: To examine the impact of important weight loss on insulin inhibition of its own secretion during experimentally induced hyperinsulinemia under euglycemic conditions. DESIGN: Longitudinal, clinical intervention study-bariatric surgery (vertical banded gastroplasty-gastric bypass-Capella technique), re-evaluation after 4 and 14 months. SUBJECTS: Nine obese patients class III (BIVII =54.6+/-2.6kg /m(2)) and nine lean subjects (BIVII = 22.7+/-0.7 kg/m(2)). MEASUREMENTS: Euglycemic hyperinsulinemic clamp (insulin infusion: 40 mU/min m(2)), C-peptide plasma levels, electrical bicimpedance methodology, and oral glucose tolerance test (OGTT). RESULTS: BIVII was reduced in the follow-up: 44.5+/-2.2 and 33.9+/-1.5 kg/m(2) at 4 and 14 months. insulin-induced glucose uptake was markedly reduced in obese patients (19.5+/-1.9 mumol/min kg FFM) and improved with weight loss, but in the third study, it was still lower than that observed in controls (35.9+/-4.0 vs 52.9+/-2.2 mumol/min kg FFM). Insulin-induced inhibition of its own secretion was blunted in obese patients (19.9+5.7%, relative to fasting values), and completely reversed to values similar to that of lean ones in the second and third studies (-60.8+/-4.2 and -54.0+/-6.1%, respectively). CONCLUSION: Weight loss in severe obesity improved insulin-induced glucose uptake, and completely normalized the insulin inhibition on its own secretion.274463468