title: Copper-mediated formation of hydrogen peroxide from the amylin peptide: a novel mechanism for degeneration of islet cells in type-2 diabetes mellitus?
abstract: Amyloid deposits derived from the amylin peptide accumulate within pancreatic islet beta-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 H(2)O(2) 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 H(2)O(2) and did not interact with copper. We conclude that the formation of H(2)O(2) from amylin could contribute to the progressive degeneration of islet cells in T2Dm.
authors.affiliation: Biomedical Sciences Unit, Department of Biological Sciences, Lancaster University, Lancaster, UK.
authors.forename: Atef
authors.initials: A
authors.lastname: Masad
authors.forename: Lee
authors.initials: L
authors.lastname: Hayes
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Tabner
authors.forename: Stuart
authors.initials: S
authors.lastname: Turnbull
authors.forename: Leanne J
authors.initials: LJ
authors.lastname: Cooper
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Fullwood
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: German
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Kametani
authors.forename: Omar M A
authors.initials: OM
authors.lastname: El-Agnaf
authors.forename: David
authors.initials: D
authors.lastname: Allsop
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007477:Ions / Q000737:chemistry; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017385:Sequence Homology
chemical_list: D000682:Amyloid; D007477:Ions; D058228:Islet Amyloid Polypeptide; D003300:Copper; D006861:Hydrogen Peroxide