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Pore formation by the cytotoxic islet amyloid peptide amylin
T A Mirzabekov1, M C Lin, B L Kagan
1Department of Psychiatry and Biobehavioral Sciences, UCLA Neuropsychiatric Institute, USA.
Abstract:
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.