Inhibitors can arrest the membrane activity of human islet amyloid polypeptide independently of amyloid formation

Thad A. Harroun, Jeremy P. Bradshaw, Richard H. Ashley

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Human islet amyloid polypeptide (hIAPP), co-secreted with insulin from pancreatic β cells, misfolds to form amyloid deposits in non-insulin-dependent diabetes mellitus (NIDDM). Like many amyloidogenic proteins, hIAPP is membrane-active: this may be significant in the pathogenesis of NIDDM. Non-fibrillar hIAPP induces electrical and physical breakdown in planar lipid bilayers, and IAPP inserts spontaneously into lipid monolayers, markedly increasing their surface area and producing Brewster angle microscopy reflectance changes. Congo red inhibits these activities, and they are completely arrested by rifampicin, despite continued amyloid formation. Our results support the idea that non-fibrillar IAPP is membrane-active, and may have implications for therapy and for structural studies of membrane-active amyloid.

Original languageEnglish
Pages (from-to)200-204
Number of pages5
JournalFEBS Letters
Volume507
Issue number2
DOIs
Publication statusPublished - 26 Oct 2001

Keywords

  • Brewster angle microscopy
  • Congo red
  • Diabetes mellitus
  • Langmuir film
  • Planar lipid bilayer
  • Rifampicin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Inhibitors can arrest the membrane activity of human islet amyloid polypeptide independently of amyloid formation. / Harroun, Thad A.; Bradshaw, Jeremy P.; Ashley, Richard H.

In: FEBS Letters, Vol. 507, No. 2, 26.10.2001, p. 200-204.

Research output: Contribution to journalArticle

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