Abstract

Methods for measuring insulin secretion and hepatic insulin extraction in vivo, e.g., hepatic vein catheterization, are invasive, and can be applied during steady state only. We introduce a noninvasive method for measuring in vivo insulin secretion and its extraction by the liver during an intravenous glucose tolerance test (IVGTT). This method is based on a minimal model of C-peptide secretion and kinetics that is used for interpreting plasma C-peptide concentration data during an IVGTT in normal humans. The model allows the reconstruction of the time course of insulin secretion and, used in conjunction with a minimal model of insulin delivery and kinetics (described in a previous study), provides a noninvasive measure of the time course of hepatic insulin extraction [H(t)]. The C-peptide model also provides a direct prehepatic measure of beta-cell sensitivity to glucose, expressed by two parameters related to first (phi IC)- and second (phi IIC)-phase insulin secretion. In the 11 healthy volunteers we studied, these parameters were 61 +/- 11 pM.min-1.mg-1.dl and 0.0154 +/- 0.0034 pM.min-2.mg-1.dl, respectively. H(t) showed an initial decrement for approximately 30-50 min (from a fasting value of 63 +/- 8% to a nadir of 53 +/- 9%) after the glucose stimulus, then a steady value of approximately 62% was reestablished and maintained throughout the experiment. The validity of the C-peptide model was further assessed by comparing its estimate of the fractional plasma clearance rate (k01) with that obtained in experiments in which biosynthetic human C-peptide was administered.(ABSTRACT TRUNCATED AT 250 WORDS)