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.