An islet amyloid polypeptide oligomer model inhibits fibril formation

linker on one polypeptide chain. In contrast to IAPP, dimIAPP did not form Thioflavin T-positive amyloid fibrils, but assembled into oligomers (dimIAPP-O) which tended to coalesce into larger clusters. IAPP fibril formation was slowed down by addition of dimIAPP-O, a finding that extends previous studies demonstrating an intrinsic inhibitory activity of off-pathway oligomers on amyloid fibril formation. Exposure of pancreatic RIN-m5f cells to dimIAPP-O and IAPP fibrils differentially activated cellular stress response. We conclude that the dimIAPP model is a useful tool to gain further insights into IAPP aggregation and to characterize the effects of off-pathway oligomers of amyloidogenic proteins.