ABSTRACT
Islet amyloid is the most common pathological finding in the islets of Langerhans and depositions are present to various degrees in the majority of individuals with type 2 diabetes. Islet amyloid polypeptide (IAPP) is main constituent of the islet amyloid and its deposition is accompanied by a 50-60 % reduction of beta-cell mass. This chapter shows that culturing isolated islets from a transgenic mouse expressing the gene for human IAPP but deficient of the endogenous IAPP gene, in presence of free fatty acids (FFA) results in the formation of an intra-granular deposition. These deposits reveal a fibrilar appearance and immunolabels with antibodies specific for human IAPP. IAPP fibrils were straight and unbranched and about 8 nm in width. Fibrils assembled in the presence of FFAs did not differ morphologically from those without FFAs. One possibility is that FFAs induce beta sheet structure of the normally non-structured peptide IAPP and thereby makes it more prone to aggregate into amyloid like fibrils.
