Influence of different concentrations of two chemical chaperones on human islet amyloid polypeptide folding under experimental conditions

Abstract

It has been implicated that type 2 diabetes mellitus is a conformational disease because amylin, a peptide produced by beta cell, undergoes an alteration in the native formation followed by selfaggregation and deposition. Amyloidogenesis causes destruction of pancreatic beta-cells. The subsequent lack of insulin leads to increased blood glucose. The main aim of this study was to investigate whether two chemical chaperones named glycerol and spermine vary islet amyloid polypeptide folding under near-physiological circumstances. For this purpose, fluorescent method was used with LS55 spectrofluorometer instrument. Results obtained from in vitro study show that after 240 h incubation by shaker incubator in 37°C, glycerol had contradictory effects on amylin folding and these effects were glycerol concentration dependent. Glycerol with concentration of 24% had the most inhibitory effect but 40 to 50% promoted amylin misfolding significantly (p<0.05). The obtained data also demonstrate that spermine with concentrations of 40, 50 and 60 µM had stimulatory effects on formation of beta-amyloid sheet significantly (p<0.05). It is concluded that amylin misfolding and cytotoxicity to beta-cells might be glycerol dose-dependent in diabetic patients.