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Free access | 10.1172/JCI110082

Increased Clearance and Degradation of [3H]Insulin in Streptozotocin Diabetic Rats: ROLE OF THE INSULIN-RECEPTOR COMPARTMENT

Jacques Philippe, Philippe A. Halban, Asllan Gjinovci, William C. Duckworth, Jurek Estreicher, and Albert E. Renold

Institut de Biochimie Clinique, University of Geneva, 1211 Geneva 4, Switzerland

Division d'Informatique Hôpital cantonal Geneva, 1211 Geneva 4, Switzerland

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Institut de Biochimie Clinique, University of Geneva, 1211 Geneva 4, Switzerland

Division d'Informatique Hôpital cantonal Geneva, 1211 Geneva 4, Switzerland

Find articles by Halban, P. in: PubMed | Google Scholar

Institut de Biochimie Clinique, University of Geneva, 1211 Geneva 4, Switzerland

Division d'Informatique Hôpital cantonal Geneva, 1211 Geneva 4, Switzerland

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

Institut de Biochimie Clinique, University of Geneva, 1211 Geneva 4, Switzerland

Division d'Informatique Hôpital cantonal Geneva, 1211 Geneva 4, Switzerland

Find articles by Duckworth, W. in: PubMed | Google Scholar

Institut de Biochimie Clinique, University of Geneva, 1211 Geneva 4, Switzerland

Division d'Informatique Hôpital cantonal Geneva, 1211 Geneva 4, Switzerland

Find articles by Estreicher, J. in: PubMed | Google Scholar

Institut de Biochimie Clinique, University of Geneva, 1211 Geneva 4, Switzerland

Division d'Informatique Hôpital cantonal Geneva, 1211 Geneva 4, Switzerland

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

Published March 1, 1981 - More info

Published in Volume 67, Issue 3 on March 1, 1981
J Clin Invest. 1981;67(3):673–680. https://doi.org/10.1172/JCI110082.
© 1981 The American Society for Clinical Investigation
Published March 1, 1981 - Version history
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Abstract

The role of the insulin-receptor compartment in the pharmacokinetics of intravenously injected insulin in rats was studied. Since streptozotocin-diabetes in rats results in increased insulin binding to tissues in vitro, insulin pharmacokinetics in streptozotocin-diabetic rats were compared to controls, using semisynthetic [3H]insulin as the tracer. The initial distribution volume for [3H]insulin was elevated by 60% in diabetic rats. By contrast, no difference in initial distribution volume for [14C]inulin was observed, and the absolute values were lower than those found for [3H]insulin. The metabolic clearance rate of [3H]insulin was elevated by 44% in diabetic rats. That these differences were the result of increased binding of insulin to a specific receptor compartment in diabetic rats was shown by three additional experiments. The first involved receptor saturation by injection of 10 U native insulin 2 min before the tracer injection, resulting in identical [3H]insulin disappearance rates in the two groups of rats. The second consisted of displacing [3H]insulin from receptors by injecting 10 U unlabeled insulin 6 min after the tracer injection. Displacement of intact [3H]insulin from receptors and subsequent reappearance in the circulation occurred in both control and diabetic animals; however, such displacement was 25% greater in the diabetic rats. Finally, treatment of diabetic rats with insulin for 8 d normalized [3H]insulin clearance even though the tracer was injected at a time when the animals were again hyperglycemic and hypoinsulinemic. This suggests that down-regulation of insulin receptors had occurred during insulin therapy. These results confirm that a specific compartment for insulin exists (the insulin-receptor compartment) and that this compartment plays an important role in insulin clearance.

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