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Original Contributions

The Limitations to and Valid Use of C-Peptide as a Marker of the Secretion of Insulin

  1. K Polonsky,
  2. B Frank,
  3. W Pugh,
  4. A Addis,
  5. T Karrison,
  6. P Meier,
  7. H Tager and
  8. A Rubenstein
  1. Departments of Medicine, Statistics, Biochemistry, and Molecular Biology, University of Chicago, Pritzker School of Medicine Chicago, Illinois Eli Lilly Research Laboratories Indianapolis, Indiana
  1. Address reprint requests to K. S. Polonsky, M.D., Department of Medicine Box 435, University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637.
Diabetes 1986 Apr; 35(4): 379-386. https://doi.org/10.2337/diab.35.4.379
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Abstract

The accuracy with which the secretion rate of insulin can be calculated from peripheral concentrations of C-peptide was investigated in conscious mongrel dogs. Biosynthetic human C-peptide and insulin were infused intraportally and their concentrations measured in the femoral artery.

During steady-state infusions of C-peptide, the peripheral concentration changed in proportion to the infusion rate and the metabolic clearance rate (5.2 ± 0.3 ml/kg/min) remained constant over a wide range of plasma concentrations.

Application of a two-compartment mathematical model, in which the model parameters were estimated from analysis of C-peptide decay curves after intravenous bolus injections, allowed the intraportal infusion rate of C-peptide to be derived from peripheral C-peptide concentrations, even under non-steady-state conditions. Estimates of the intraportal infusion rate based on this model were 102.4 ± 2.6% of the actual infusion rate as it was increasing and 102.3 ± 5.5% of this rate as it was falling.

The peripheral C-peptide : insulin molar ratio was influenced by the rate at which equimolar intraportal infusions of C-peptide and insulin were changed. The baseline C-peptide : insulin molar ratio (4.1 ± 0.9) increased to peak values of 8.2 ± 0.6,10.3 ± 2.0, and 14.9 ±1.3 when the infusion rate was increased and then decreased rapidly. Peak values of only 5.7 ±1.2 were found if the intraportal infusion rate was changed slowly.

In conclusion: (1) under steady-state conditions the secretion rate of insulin can be calculated as the product of the peripheral concentration of C-peptide and its MCR; (2) under non-steady-state conditions, however, application of more complex mathematical models, such as the two-compartment model used in the present study, allows insulin secretion rates to be accurately calculated at discrete time points; and (3) under non-steady-state conditions the C-peptide:insulin molar ratio is influenced not only by the extent of hepatic insulin extraction but by other factors, including the rate of change of insulin secretion and the clearance rate of C-peptide. Changes in this ratio should therefore not be assumed to reflect changes in hepatic insulin extraction.

  • Received March 28, 1985.
  • Revision received October 28, 1985.
  • Copyright © 1986 by the American Diabetes Association

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April 1986, 35(4)
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The Limitations to and Valid Use of C-Peptide as a Marker of the Secretion of Insulin
K Polonsky, B Frank, W Pugh, A Addis, T Karrison, P Meier, H Tager, A Rubenstein
Diabetes Apr 1986, 35 (4) 379-386; DOI: 10.2337/diab.35.4.379

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The Limitations to and Valid Use of C-Peptide as a Marker of the Secretion of Insulin
K Polonsky, B Frank, W Pugh, A Addis, T Karrison, P Meier, H Tager, A Rubenstein
Diabetes Apr 1986, 35 (4) 379-386; DOI: 10.2337/diab.35.4.379
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