Islet Amyloid Polypeptide and Diabetes

Gunilla   T.   Westermark; Per      Westermark

Abstract

Islet amyloid polypeptide (IAPP, amylin) is a 37 amino acid residue hormone expressed mainly by pancreatic islet beta cells and to less extent by some gastrointestinal endocrine cells and by certain regions in central nervous system. In experimental systems a number of different effects have been ascribed to IAPP but the in vivo importance of many of them is still unknown. At least effects on the central nervous system and on endocrine pancreatic cells are likely to be physiologically relevant. In these tissues calcitonin receptors and receptor activity-modifying proteins (RAMPs) 1 and 3, creating high affinity IAPP receptors have been identified. How expression of the components of these complexes are regulated and how further signaling is conducted are more or less unknown. IAPP is most well-known for its ability to aggregate into amyloid fibrils in islets of Langerhans in association with type 2 diabetes leading to loss of beta cells. In addition, amyloid is deposited between endocrine cells and between such cells and capillaries and most likely disturbs important interactions between the cells. How IAPP receptor complexes are affected by the amyloid formation process or by amyloid itself, or vice versa, are completely unknown.

Keywords: Amylin, amyloid, fibril, calcitonin receptor, islet amyloid polypeptide, receptor activity-modifying proteins, type 2 diabetes, IAPP, RAMP.