Amyloid beta antagonizes insulin promoted secretion of the amyloid beta protein precursor

Xie Ling, R. N. Martins*, M. Racchi, S. Craft, E. Helmerhorst

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

Amyloid β (Aβ) peptides are direct competitive inhibitors of insulin binding and action [25]. We demonstrate that Aβ peptides can inhibit the effect of insulin on the metabolic processing of the amyloid β protein precursor (AβPP). As evidence emerges concerning the role of insulin and insulin like growth factors (IGFs) in learning and memory, recent findings have suggested that insulin may have a significant role in the pathogenetic pathways leading to Alzheimer's disease (AD). As an example several investigators have demonstrated upregulation of insulin receptors and defective insulin receptor signal transduction in AD brains. Moreover insulin has been shown to positively modulate AßPP proteolytic processing. The fact that insulin and Aβ appear to share a common system for degradation and disposal as they are both substrates of the insulin degrading enzyme (IDE) suggested the possibility of a reciprocal interference. Here we report that Aa can directly interfere with insulin receptor signalling inhibiting the autophosphorylation of partially purified insulin receptors. As a consequence of such interaction we also demonstrate that Aβ blocks the effect of insulin on the release of sAßPPα in chinese hamster ovaries (CHO) cells transfected with insulin receptors.

Original languageEnglish
Pages (from-to)369-374
Number of pages6
JournalJournal of Alzheimer's Disease
Volume4
Issue number5
Publication statusPublished - Oct 2002
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Amyloid β
  • Amyloid β-protein precursor protein
  • Insulin
  • Insulin receptor autophosphorylation

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