Physiological and Pathophysiological Role of Islet Amyloid Polypeptide (IAPP, Amylin)

Abstract

IAPP has a number of effects which may be of physiological relevance. Islet amyloid, which earlier was regarded as a non-important degenerative product, most likely plays a central role in the loss of β-cells in type 2 diabetes and probably in transplanted human islets. Taken together the results from human and animal studies show that amyloid develops before β-cell deficiency, and the occurrence of oligomers and amyloid intracellular induces β-cell death. Prevention of islet amyloid most likely will save β-cells and extend hormone secretion. Islet Amyloid PolypeptideIslet amyloid polypeptide (IAPP) was originally isolated as the major peptide constituent of the amyloid from an insulinoma [1] and subsequently isolated from amyloid deposits present in the islet of Langerhans from patients with type 2 diabetes [2,3]. The 37 residue polypeptide proved to have an earlier unknown sequence, but showed an almost 50% identity to the known calcitonin gene-related peptide [4]. Other nomenclatures for IAPP are amylin [5], diabetes-associated peptide [6] and IAP (insulinoma amyloid peptide) [1]. IAPP is phylogenetically well preserved and found in all mammals where it has been looked for [7][8][9][10] and also in an avian [11] and fish [12].During embryogenesis in mice, IAPP was detected in the primordia at E12 and the immunoreactivity was restricted to the simultaneously occurring insulinexpressing cells [13]. In human, IAPP immune-reactive cells were demonstrated