Structural basis and functional significance of food-derived inhibitors of islet amyloid polypeptide fibrillation toward antidiabetic effects

Abstract

Several approaches are taken in type 2 diabetes (T2D) management to increase insulin effectiveness through the reduction of hepatic glucose production, release and reabsorption, and enzyme inhibition. These approaches are geared toward treating the downstream effects of β-cell malfunction rather than minimizing the initial source of stress contributing to the loss of β-cell mass. Islet amyloid polypeptide (IAPP), or amylin, causes a loss of β-cell mass upon fibrillation, a common feature in T2D development. Thus, IAPP fibrillation is emerging as a physiological target in mitigating β-cell cytotoxicity. This paper discusses recent advances in the inhibition of IAPP fibrillation by food-derived polyphenols, peptides, and polysaccharides. Structure-activity relationships suggest the importance of motifs such as catechol-containing groups of polyphenols in increasing anti-fibrillation activity.