Relationship between Peripheral Concentrations of C-Peptide and Insulin and their Secretion Rates in the Dog

Estimation of the insulin secretory rate from peripheral C-peptide concentrations depends upon the following characteristics of C-peptide kinetics: (a) equimolar secretion of insulin and C-peptide by pancreatic beta cells; (b) negligible hepatic extraction of C-peptide; (c) constant metabolic clearance rate (MCR) ofC-peptide over a physiological and pathophysiological range of plasma levels; and (d) proportional changes in the secretion rate of C-peptide and its peripheral con- centrations under varying physiological conditions. In the present experiments, the relationship between a variable intraportal infusion of C-peptide and its concentration in the femoral artery was explored in 12 pancreatectomized dogs. As the infusion of C-peptide was rapidly increased, the magnitude of its peripheral concentration initially increased less than the infusion rate by 20-30%. After an equilibration period of -30 min, however, further increases and decreases in the intraportal infusion were accompanied by nearly pro- portional changes in its peripheral concentration. Esti- mates of the amount of C-peptide infused during the experiment based on the steady state C-peptide MCR and its peripheral concentration were within 20% of the amount of C-peptide actually infused. These experiments demonstrate that the portal delivery rate of C-peptide can be calcuated from its MCR and peripheral concen- tration in the dog. They also provide a basis for testing