Copper-mediated formation of hydrogen peroxide from the amylin peptide: A novel mechanism for degeneration of islet cells in type-2 diabetes mellitus?

Atef Masad, Lee Hayes, Brian J. Tabner, Stuart Turnbull, Leanne J. Cooper, Nigel J. Fullwood, Matthew J. German, Fuyuki Kametani, Omar Ali El-Agnaf, David Allsop

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Abstract

Amyloid deposits derived from the amylin peptide accumulate within pancreatic islet β-cells in most cases of type-2 diabetes mellitus (T2Dm). Human amylin 'oligomers' are toxic to these cells. Using two different experimental techniques, we found that H2O2 was generated during the aggregation of human amylin into amyloid fibrils. This process was greatly stimulated by Cu(II) ions, and human amylin was retained on a copper affinity column. In contrast, rodent amylin, which is not toxic, failed to generate any H2O2 and did not interact with copper. We conclude that the formation of H2O2 from amylin could contribute to the progressive degeneration of islet cells in T2Dm.

Original languageEnglish
Pages (from-to)3489-3493
Number of pages5
JournalFEBS Letters
Volume581
Issue number18
DOIs
Publication statusPublished - 24 Jul 2007
Externally publishedYes

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Keywords

  • Amplex red
  • Amylin
  • Copper
  • Electron spin resonance
  • Hydrogen peroxide
  • Type-2 diabetes

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Masad, A., Hayes, L., Tabner, B. J., Turnbull, S., Cooper, L. J., Fullwood, N. J., German, M. J., Kametani, F., Ali El-Agnaf, O., & Allsop, D. (2007). Copper-mediated formation of hydrogen peroxide from the amylin peptide: A novel mechanism for degeneration of islet cells in type-2 diabetes mellitus? FEBS Letters, 581(18), 3489-3493. https://doi.org/10.1016/j.febslet.2007.06.061