Pore formation by the cytotoxic islet amyloid peptide amylin.
Amylin is a 37-amino acid cytotoxic constituent of amyloid deposits found in the islets of Langerhans of patients with type II diabetes. Extracellular accumulation of this peptide results in damage to insulin-producing beta cell membranes and cell death. We report here that at cytotoxic concentrations, amylin forms voltage-dependent, relatively nonselective, ion-permeable channels in planar phospholipid bilayer membranes. Channel formation is dependent upon lipid membrane composition, ionic strength, and membrane potential. At 1-10 microM, cytotoxic human amylin dramatically increases the conductance of lipid bilayer membranes, while non-cytotoxic rat amylin does not. We suggest that channel formation may be the mechanism of cytotoxicity of human amylin.
Mirzabekov
T A
TA
Department of Psychiatry and Biobehavioral Sciences, UCLA Neuropsychiatric Institute, USA.
Lin
M C
MC
Kagan
B L
BL
D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D002463:Cell Membrane Permeability; D003603:Cytotoxins / Q000737:chemistry; D004553:Electric Conductivity; D006801:Humans; D007473:Ion Channels / Q000737:chemistry*; D058228:Islet Amyloid Polypeptide; D008051:Lipid Bilayers; D008565:Membrane Proteins / Q000737:chemistry; D051381:Rats
D000682:Amyloid; D003603:Cytotoxins; D007473:Ion Channels; D058228:Islet Amyloid Polypeptide; D008051:Lipid Bilayers; D008565:Membrane Proteins