Recent Insights in Islet Amyloid Polypeptide-Induced Membrane Disruption and Its Role in -Cell Death in Type 2 Diabetes Mellitus

Figure 3

Simplified schematic representation of the different models of hIAPP-membrane interaction in relation to membrane damage and hIAPP cytotoxicity. The red rectangles show the toxic species and the red arrows show the toxic processes according to different hypotheses. The black circle represents a phospholipid membrane (vesicle), the grey circles represent hIAPP monomers, and clusters of 4 or more circles represent hIAPP oligomers and hIAPP fibrils, respectively. Membrane damage is schematically indicated by the grey arrows. Model (1) includes two steps: (i) formation of soluble hIAPP oligomers, (ii) interaction of the toxic oligomers with the membrane leading to membrane damage. Model (2) includes three steps: (i) binding of monomeric, random coil hIAPP to the membrane and folding to -helix, (ii) oligomer formation of membrane-bound hIAPP, and (iii) interaction of the toxic hIAPP oligomer with the membrane leading to membrane damage. Model (3) includes 3 steps: (i) interaction of monomeric and possibly oligomeric hIAPP to the membrane, (ii) growth of hIAPP fibrils at the membrane (red arrows) leading to a forced change in membrane morphology and concomitant membrane disruption, and (iii) detachment of mature fibrils from distorted membrane.