Insulin and C-peptide secretion and kinetics in humans: direct and model-based measurements during OGTT

To directly evaluate prehepatic secretion of pancreatic hormones during a 3 -h oral glucose tolerance test (OGTT), we measured insulin and C-peptide in six healthy control, six obese, and six type 2 diabetic subjects in the fe moral artery and hepatic vein by means of the hepatic catheterization techn ique. Hypersecretion in obesity was confirmed (309 +/- 66 nmol in obese vs. 117 +/- 22 in control and 79 +/- 13 in diabetic subjects, P less than or e qual to 0.01), whereas early phase secretion was impaired in diabetes. We a lso measured hepatic insulin extraction (higher in diabetic than in control subjects, P = 0.03) and insulin clearance. The measured data were also use d to validate a previously proposed mathematical model, developed to quanti fy prehepatic secretion, hepatic insulin extraction, and insulin clearance during OGTT, when C-peptide and insulin concentrations are systemically mea sured. We found good correspondence between experimental data and model est imates for prehepatic insulin secretion (P > 0.3, r(2) = 0.93), whereas est imation of hepatic insulin extraction and insulin clearance needs further i nvestigation for improvement.