C-peptide metabolism and the liver

It is generally assumed that C-peptide is not degraded in the liver to any significant extent. This assumption is, however, based on indirect evidence. We therefore measured the hepatic extraction ratio (R) of insulin and C-peptide in anesthetized pigs with simultaneous sampling of portal and hepatic venous blood. Blood samples were taken at one-minute intervals for 10 minutes during basal (unstimulated) experimental conditions as well as after intravenous injection of 1 mg. glucagon into four normal-weight and four obese pigs. The hepatic extraction ratio of insulin or C-peptide was calculated as the portal concentration minus the hepatic concentration divided by the portal concentration. The average pre- and poststimulatory molar ratios of C-peptide to insulin were 1.5 ± 0.11 (S.E.M.) and 1.2 ± 0.06 in portal blood and 3.4 ± 0.21 and 2.2 ± 0.08 in hepatic blood. For all pigs the mean Rc-peptide was 0.30 ± 0.03 and 0.33 ± 0.02 pre- and poststimulatory, respectively. The corresponding figures for Rinsulin (0.71 ± 0.02 and 0.61 ± 0.02) were both significantly higher (p < 0.01). The mean R-values for C-peptide and insulin were consistently higher in obese pigs than in normal-weight pigs (p < 0.01). Additional experiments in two normal-weight pigs showed that ligation of the hepatic artery elicited a significant fall of mean Rc-peptide, which, however, never became less than 0.12. These results suggest that besides the wellknown hepatic extraction of insulin, the livers of anesthetized pigs also extract significant amounts of endogenous C-peptide. Hepatic extraction of C-peptide is, however, about 50 per cent lower than that of insulin.