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 β 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 μM, cytotoxic human amylin dramatically increases the conductance of lipid bilayer membranes, while noncytotoxic rat amylin does not. We suggest that channel formation may be the mechanism of cytotoxicity of human amylin.