Calculated pattern of intraportal insulin appearance without independent assessment of C-peptide kinetics.

Prehepatic beta-cell insulin release can be calculated with C-peptide measurements, but this requires independent determination of kinetics of C-peptide disappearance from plasma. We introduce an approach by which a prehepatic insulin release pattern is calculated from plasma insulin and C-peptide, without separate C-peptide kinetic analysis. Human insulin and C-peptide were infused intraportally into conscious dogs (n = 11) at equimolar rates; endogenous insulin and C-peptide release were suppressed with somatostatin (0.8 micrograms . kg-1 . min-1). Insulin and C-peptide were infused at basal and equimolar rates (range 19-72 pmol/min in dogs), and the infusions were slowly increased, in stepwise fashion, to a maximum at 60 min (range 152-613 pmol/min) and subsequently renormalized at either 85 (n = 6) or 195 (n = 5) min. Plasma insulin and C-peptide measurements were described simultaneously by a composite model of insulin and C-peptide plasma kinetics, with the molar intraportal appearance rate due to the infusion R(t) as an unknown input for both insulin and C-peptide catabolism. The model assumes one-compartment disappearance kinetics for both peptides. Fitting the model to the measured insulin and C-peptide data, we were able to compute the insulin-appearance pattern accurately for every experiment; calculated and actual secretion rates were highly correlated (r = .93-.97) and had very similar temporal patterns. Also calculated were the fractional disappearance rates for human insulin (t1/2 = 6.9 min) and C-peptide (t1/2 = 14 min) in the dog, as well as the C-peptide distribution volume (12.3 +/- 0.5% body wt).(ABSTRACT TRUNCATED AT 250 WORDS)