Islet amyloid polypeptide-induced membrane leakage involves uptake of lipids by forming amyloid fibers

Research output: Contribution to journalArticle

Abstract

Fibril formation of islet amyloid polypeptide (IAPP) is associated with cell death of the insulin-producing pancreatic beta-cells in patients with Type 2 Diabetes Mellitus. A likely cause for the cytotoxicity of human TAPP is that it destroys the barrier properties of the cell membrane. Here, we show by fluorescence confocal microscopy on lipid vesicles that the process of hIAPP amyloid formation is accompanied by a loss of barrier function, whereby lipids are extracted from the membrane and taken up in the forming amyloid deposits. No membrane interaction was observed when preformed fibrils were used. It is proposed that lipid uptake from the cell membrane is responsible for amyloid-induced membrane damage and that this represents a general mechanism underlying the cytotoxicity of amyloid forming proteins. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Details

Authors
  • Emma Sparr
  • M F M Engel
  • D V Sakharov
  • M Sprong
  • J Jacobs
  • B de Kruijff
  • J W M Hoppener
  • J A Killian
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biological Sciences

Keywords

  • Amylin, Type II diabetes mellitus, Protein–membrane interaction, Amyloid, Model membrane
Original languageEnglish
Pages (from-to)117-120
JournalFEBS Letters
Volume577
Issue number1-2
Publication statusPublished - 2004
Publication categoryResearch
Peer-reviewedYes