en
Scientific article
English

Increased clearance and degradation of [3H]insulin in streptozotocin diabetic rats

Published inThe Journal of clinical investigation, vol. 67, no. 3, p. 673-680
Publication date1981
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 [(3)H]insulin as the tracer. The initial distribution volume for [(3)H]insulin was elevated by 60% in diabetic rats. By contrast, no difference in initial distribution volume for [(14)C]inulin was observed, and the absolute values were lower than those found for [(3)H]insulin. The metabolic clearance rate of [(3)H]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 [(3)H]insulin disappearance rates in the two groups of rats. The second consisted of displacing [(3)H]insulin from receptors by injecting 10 U unlabeled insulin 6 min after the tracer injection. Displacement of intact [(3)H]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 [(3)H]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.

Keywords
  • Animals
  • Diabetes Mellitus, Experimental/ metabolism
  • Hormones/metabolism
  • Insulin/administration & dosage/ metabolism
  • Kinetics
  • Metabolic Clearance Rate
  • Rats
  • Receptor, Insulin/ metabolism
  • Streptozocin
Citation (ISO format)
PHILIPPE, Jacques et al. Increased clearance and degradation of [3H]insulin in streptozotocin diabetic rats. In: The Journal of clinical investigation, 1981, vol. 67, n° 3, p. 673–680. doi: 10.1172/JCI110082
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Identifiers
ISSN of the journal0021-9738
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