Since the C-peptide/insulin ratio is reduced after oral glucose ingestion, the incretin hormone gastric inhibitory polypeptide (GIP) has been assumed to decrease hepatic insulin extraction. It was the aim of the present study to evaluate the effects of GIP on insulin extraction. Seventy-eight healthy subjects (27 male, 51 female, 43+/-11 years) were subjected to (a). an oral glucose tolerance test and (b). an intravenous injection of 20 pmol GIP/kg body weight, with capillary and venous blood samples collected over 30 min for insulin, C-peptide and GIP (specific immunoassays). Following GIP administration, plasma concentrations of total and intact GIP reached to peak levels of 80+/-7 and 54+/-5 pmol/l, respectively (p<0.0001). The rise in insulin after oral glucose and after intravenous GIP administration significantly exceeded the rise in C-peptide (p<0.0001). Estimating insulin extraction from the total integrated insulin and C-peptide concentrations (AUCs), only the oral glucose load (p<0.0001), but not the intravenous GIP administration (p=0.18) significantly reduced insulin clearance. Therefore, insulin clearance is reduced after an oral glucose load. This effect does not appear to be mediated by GIP.