Accuracy of C-peptide:insulin molar ratio as a measure of hepatic removal of insulin

• Published in: Diabetes research and clinical practice Vol. 4; no. 1; pp. 37 - 43
• Main Authors: Berzins, R., Wieczorek, K.R., Rajotte, R.V., Molnar, G.D., Tam, Y.K., McGregor, J.R., Fawcett, D.M.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.11.1987
• Subjects: Animals; C-peptide; C-Peptide - blood; Dogs; Electromagnetic Phenomena; Female; Hepatic extraction; Insulin; Insulin - blood; Insulin - metabolism; Kinetics; Liver - metabolism; Liver Circulation; Male; Somatostatin - pharmacology; Hepatic extraction; Insulin; C-peptide
• ISSN: 0168-8227; 1872-8227
• DOI: 10.1016/S0168-8227(87)80031-1

We measured transhepatic C-peptide and insulin concentrations in plasma, and hepatic removal of insulin, to examine whether the practice of reporting the C-peptide:insulin molar ratio as a measure of the hepatic removal of insulin is valid. In anesthetized dogs ( n=6), during electromagnetic hepatic blood flow monitoring, endogenous insulin was suppressed with somatostatin, while equimolar proportions of porcine insulin and simian C-peptide (2.4 and 6.0 pmol/kg·min) were infused during two consecutive 45-min periods. Insulin reached steady state within 20 min ( t 1/2 = 4.5 min); however, C-peptide concentrations continued to rise ( t 1/2 = 12.5 min). The ratio decreased when the peptide infusion was changed to the higher rate and increased when it was stopped, reflecting the more rapid removal of insulin than of C-peptide. Hepatic removal of insulin remained constant during the two infusion periods (average 60% extraction) and never correlated with the changing molar ratios. Hepatic net flux of insulin correlated with the ratio ( P<0.05) only while plasma insulin concentrations were rising during constant-rate infusion. We therefore conclude that the molar ratio is not a reliable measure of the hepatic removal of insulin during non-steady states of insulin or C-peptide.