Short Peptide Segment and Insulin Co-Assembly Forms Cytotoxic Oligomers

Abstract

Insulin assembly follows different pathways under different environments. But the mechanism of insulin assembly and the pathology of insulin-related amyloidosis diseases remain unclear. This work, illustrating different pathways of insulin aggregation induced by short peptide segment, may shed light on these research areas. We find that the short peptide segment LVEALYL (7aa, a segment of insulin B chain) can alter the pathway of insulin aggregation and induce the generation of highly toxic oligomers. However, when a bulky cyclen is attached to the peptide segment, β-sheet enriched fibrils will be formed again. This phenomenon may be induced by the disruptive effect of cyclen on the interaction between the short peptide and insulin, which alters the aggregation pathway.