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Research Article Free access | 10.1172/JCI106886

The Metabolism of Proinsulin and Insulin by the Liver

A. H. Rubenstein, L. A. Pottenger, M. Mako, G. S. Getz, and D. F. Steiner

Department of Medicine, University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637

Department of Pathology, University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637

Department of Biochemistry, University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637

Find articles by Rubenstein, A. in: PubMed | Google Scholar

Department of Medicine, University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637

Department of Pathology, University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637

Department of Biochemistry, University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637

Find articles by Pottenger, L. in: PubMed | Google Scholar

Department of Medicine, University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637

Department of Pathology, University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637

Department of Biochemistry, University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637

Find articles by Mako, M. in: PubMed | Google Scholar

Department of Medicine, University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637

Department of Pathology, University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637

Department of Biochemistry, University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637

Find articles by Getz, G. in: PubMed | Google Scholar

Department of Medicine, University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637

Department of Pathology, University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637

Department of Biochemistry, University of Chicago, Pritzker School of Medicine, Chicago, Illinois 60637

Find articles by Steiner, D. in: PubMed | Google Scholar

Published April 1, 1972 - More info

Published in Volume 51, Issue 4 on April 1, 1972
J Clin Invest. 1972;51(4):912–921. https://doi.org/10.1172/JCI106886.
© 1972 The American Society for Clinical Investigation
Published April 1, 1972 - Version history
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Abstract

The removal of bovine proinsulin by the isolated perfused rat liver has been studied and the results compared with the removal of insulin. At high concentrations of insulin (> 180 ng/ml) the removal process was saturated and the t½ varied between 35 and 56 min. With low initial insulin levels the disappearance followed first-order kinetics, the mean regression coefficient being — 0.022, t½ 13.8 min, and the hepatic extraction 4.0 ml/min. The results with proinsulin were in striking contrast to these findings. At both high and low concentrations the hepatic removal of proinsulin was considerably slower, averaging 10-15 times less than that of insulin. Specific immunoassay techniques and gel filtration of samples taken from perfusions to which both labeled and unlabeled proinsulin had been added did not show conversion to either insulin or the C-peptide.

Bovine and rat 131I-labeled proinsulins were degraded more slowly than bovine insulin-131I by bovine and rat liver homogenates. Both proinsulin and insulin inhibited the degradation of insulin-131I, equimolar quantities of proinsulin being 2-5 times less effective than insulin.

These results indicate significant differences in the capacity of the liver to remove and degrade insulin and proinsulin. The low hepatic extraction of proinsulin may account for its prolonged half-life in vivo and contribute to its relatively high plasma concentration in the fasting state. Furthermore this finding will have to be taken into account in the interpretation of changes in the proinsulin:insulin ratios in peripheral blood in a variety of metabolich situations.

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