Figure 4.

Causative factors of toxic oligomer formation.

Notes: Mechanistic factors that result in the generation of oligomers from pro-IAPP include the absence of PC2 enzyme, deamidation, reduction of the disulfide bond, environmental factors in the cell, genetic mutations, copper metal ions, and heparin-induced cell apoptosis. The barrel-stave model and carpet model demonstrate known methods by which amyloidogenic peptides can trigger membrane destabilization and disruption. In addition, both intra- and extracellular aggregation may be involved in these cytotoxic processes, although they most likely occur intracellularly. The mechanisms contributing to inhibitory effects such as copper ion chelators and rifampicin are indicated.

Abbreviations: IAPP, islet amyloid polypeptide; PARP, poly (ADP-ribose) polymerase; ROS, reactive oxygen species; PC1/3, proprotein convertase 1/3; PC2, proprotein convertase 2; PAM, peptidylglycine α-amidating monooxygenase; Cu(II), copper (II) ion.