Abstract

Misfolded amylin, the human polypeptide hormone, forms amyloid deposits in pancreatic islets. These amyloid deposits contribute to the dysfunction of beta-cells and the loss of beta-cell mass in type 2 diabetes mellitus (T2DM). Inhibition of amylin fibrillization has been regarded as a potential therapeutic approach for T2DM. Using fluorescence spectroscopic analysis with thioflavin T, the role of two naturally occurring flavonoids named myricetin and epigallocatechin gallate on human amylin hormone fibrillization and destabilization of fibrillar aggregates were examined under near physiological conditions. The results showed that after 168 h incubation by shaker incubator in 37°C. Myricetin at 10 and 40 µM repressed amylin amyloid formation by 25.3 and 22.4%, respectively (p<0.05), and the similar values of epigallocatechin gallate inhibited the formation of β-sheet structure by 18.1 and 16.7%, respectively (p<0.05). The obtained data also confirmed that amyloidal sheet opening was induced by myricetin and epigallocatechin gallate significantly (p<0.05). Therefore, it was concluded that islet amyloid cytotoxicity to β-cells may be reduced by these two flavonoids, and these compounds should be key molecules for the development of the therapeutics for diabetes mellitus.

Key words: Human islet amyloid polypeptide, hyperglycemia, myricetin, epigallocatechin gallate, flavonoids.