To study the metabolic effects of normalizing body weight, a frequently sampled iv glucose tolerance test (0.3 g/kg) was performed before [body mass index (BMI), 37.7 +/- 0.5 kg/m2] and 14 +/- 2 months after successful gastroplasty (BMI, 23.7 +/- 0.6 kg/m2) in eight obese women and, for comparison, in eight age- and weight-matched nonobese control women (BMI, 23.6 +/- 0.7 kg/m2). All subjects had normal oral glucose tolerance. The insulin secretion rate (ISR) was derived by deconvolution of plasma C-peptide levels and the insulin MCR (MCRI) by dividing the 0-180 min area under the curve (AUC) of ISR by that of plasma insulin levels (IRI). The insulin sensitivity index (SI) and the glucose effectiveness index (SG) were calculated using Bergman's minimal model. Before gastroplasty, obese subjects showed higher AUC-IRI (P < 0.001) and AUC-ISR (P < 0.02), lower MCRI (P < 0.005) and SI (P < 0.002), but similar SG values, compared to nonobese controls. After gastroplasty, the AUC-IRI dramatically decreased, due to both a reduction of AUC-ISR (from 58,252 +/- 8,437 to 36,675 +/- 4,274 pmol; P < 0.05) and an increase in MCRI (from 658 +/- 117 to 1,299 +/- 127 mL/min.m-2; P < 0.02). SI significantly rose from 4.74 +/- 0.74 to 9.15 +/- 0.96 10(-5) min-1/pmol.L (P < 0.01), whereas SG remained unchanged. All of these parameters became similar to those in nonobese controls (respectively, 32,522 +/- 3,458, 1,180 +/- 101, and 8.48 +/- 1.25; all P = NS). In conclusion, after gastroplasty-induced normalization of body weight, postobese women recover normal insulin secretion, clearance, and action on glucose metabolism.