Chitosan oligosaccharides inhibit the fibrillation of insulin and disassemble its preformed fibrils

Abstract

In the current study, we first established that chitosan oligosaccharides (COS) have significant anti-fibrillogenic and fibril-destabilising effects on bovine insulin in vitro that proportionally expand with concentration growth. The obtained data were supported by the Thioflavin T (ThT) assay, circular dichroism (CD), attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy, and atomic force microscopy (AFM). Interestingly, coincubation of insulin with COS in the ratio of 1 to 10 over 48 h at 37 °C leads to full prevention of insulin aggregation, and in the case of preformed fibrils, results in their destabilisation and disaggregation. Moreover, both a cationic polymer of allylamine (PAH) and a sulphated oligosaccharide (CROS) prepared from carrageenan had no inhibitory effect on insulin amyloid formation. Thus, we proposed that COS modulates insulin amyloid formation due to the presence of linear sugar units, the degree of polymerization, and the free amino group providing a positive charge. These findings highlight the potential implications of COS as a promising substance for the treatment of insulin-dependent diabetes mellitus and localised insulin-derived amyloidosis and, moreover, provide a new insight into the mechanism of the anti-diabetic and antitoxic properties of chitosan and chitosan-based agents.