From barnyard to bedside: using interspecies variants to inform the rational design of novel analogs of islet amyloid polypeptide

Abstract

Islet amyloid polypeptide (IAPP, also known as amylin) is a 37-residue, neuropancreatic hormone that is co-secreted with insulin by islet β-cells and plays an important role in glycemic control. The peptide is linked to diabetes mellitus, forming extracellular amyloid deposits in type 2 disease and largely absent in type 1 disease. IAPP is found in all vertebrates and the sequence is well conserved, but some variants exhibit decreased in vitro amyloidogenicity and enhanced solubility in formulation.