Copper-mediated formation of hydrogen peroxide from the amylin peptide: a novel mechanism for degeneration of islet cells in type-2 diabetes mellitus?
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.
Masad
Atef
A
Biomedical Sciences Unit, Department of Biological Sciences, Lancaster University, Lancaster, UK.
Hayes
Lee
L
Tabner
Brian J
BJ
Turnbull
Stuart
S
Cooper
Leanne J
LJ
Fullwood
Nigel J
NJ
German
Matthew J
MJ
Kametani
Fuyuki
F
El-Agnaf
Omar M A
OM
Allsop
David
D
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
D000682:Amyloid; D007477:Ions; D058228:Islet Amyloid Polypeptide; D003300:Copper; D006861:Hydrogen Peroxide