Insulin acts intracellularly on proteasomes through insulin-degrading enzyme

William C. Duckworth, Robert G. Bennett, Frederick G. Hamel

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Insulin decreases cellular protein degradation, but the mechanism of this action is poorly understood. We have shown that insulin can have an inhibitory effect on the action of the proteasome in vitro, which requires the presence of insulin degrading enzyme (IDE). In this study we have used an antibody which inhibits the activity of IDE to show that IDE is required for insulin inhibition of protein degradation in intact cells. The anti-IDE antibody blocked the insulin effect on cellular degradation of proteins prelabeled with radioactive amino acids. The anti-IDE antibody also decreased insulin inhibition of proteasome degradation of a specific substrate in intact cells. These data suggest that insulin works intracellularly via IDE to inhibit protein degradation by the proteasome. Thus, IDE may function as an intracellular mediator for insulin effects on protein degradation. This is a novel signal transduction mechanism for peptide hormones.

Original languageEnglish (US)
Pages (from-to)390-394
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - Mar 17 1998


  • Insulin
  • Insulin-degrading enzyme
  • Protease
  • Proteasome
  • Signal transduction

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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