ABSTRACT
Islet amyloid polypeptide (IAPP), also known as amylin, is a polypeptide hormone co-secreted with insulin by pancreatic ß-cells. In general, IAPP is soluble and lacks a defined structure. However, under certain conditions, these peptides tend to aggregate into soluble oligomers, eventually forming insoluble amyloid fibrils with typical cross-ß-sheet structures. Amylin aggregates, therefore, have been regarded as one of the hallmarks of type II diabetes (T2D). Among these aggregated species, oligomers were shown to exhibit significant cytotoxicity, leading to impaired ß-cell function and reduced ß-cell mass. Monitoring of oligomer appearance during IAPP fibrillation is of particular interest. In this study, we successfully grafted an aggregation-induced emission molecule, tetraphenylethylene (TPE), at the N-terminus of IAPP. By mixing a small amount of TPE-labeled IAPP with unlabeled IAPP, we were able to detect an increase in TPE fluorescence during the nucleation phase of IAPP aggregation in vitro. It may enable real-time monitoring of IAPP oligomer formation and is further applied in the diagnosis of T2D.