Insulin is a kinetic but not a thermodynamic inhibitor of amylin aggregation.
One of the most important pathological features of type 2 diabetes is the formation of islet amyloid, of which the major component is amylin peptide. However, the presence of a natural inhibitor such as insulin may keep amylin stable and physiologically functional in healthy individuals. Some previous studies demonstrated that insulin was a potent inhibitor of amylin fibril formation in vitro, but others obtained contradictory results. Hence, it is necessary to elucidate the effects of insulin on amylin aggregation. Here we report that insulin is a kinetic inhibitor of amylin aggregation, only keeping its inhibitory effect for a limited time period. Actually, insulin promotes amylin aggregation after long-term incubation. Furthermore, we found that this promotional effect could be attributed to the copolymerization of insulin and amylin. We also found that insulin copolymerized with amylin monomer or oligomer rather than preformed amylin fibrils. These results suggest that the interaction between insulin and amylin may contribute not only to the inhibition of amylin aggregation but also to the coaggregation of both peptides in type 2 diabetes.
Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing, China.
Wei
W
Cui
Jing-Wen
JW
Ma
Peng
P
Lei
Wei-Hui
WH
Wu
Ye-Ping
YP
Yu
Yu
Y
Xiang
Ai-Jun
AJ
Tong
Yu-Fen
YF
Zhao
Yan-Mei
YM
Li
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007328:Insulin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D058228:Islet Amyloid Polypeptide; D007700:Kinetics; D008027:Light; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D012542:Scattering, Radiation; D013816:Thermodynamics
D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D011108:Polymers