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)
D000818:Animals; D002096:C-Peptide / Q000097:blood*; D004285:Dogs; D006207:Half-Life; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D011169:Portal Vein; D013004:Somatostatin / Q000494:pharmacology
D002096:C-Peptide; D007328:Insulin; D013004:Somatostatin