S3.3 - Latest advances in amylin therapeutics for obesity treatment

Abstract The pancreatic hormone amylin has originally been discovered in and isolated from pancreatic islet amyloid deposits. In few species only, including primates and felines, the amylin molecule has the propensity to aggregate into oligomers and eventually mature amyloid fibrils. However, monomeric hormonal amylin produces a large variety of beneficial metabolic effects that make the non-fibrillar forms of amylin a fascinating candidate for the treatment of metabolic diseases. Amylin is co-synthesized and co-secreted with insulin, and it is an important control of eating, mainly by its physiological effect on meal-ending satiation. Chronically, amylin and its receptor analogues also lead to substantial weight loss. Here, I will review the current knowledge on the central nervous system pathways mediating amylin's metabolic effects and how this may translate in effective pharmacotherapy. Amylin receptor pharmacology is complex because of the existence of several distinct amylin receptor subtypes, and we only start to understand the specific actions mediated by these subtypes. The latter aspect is also relevant to understand potential differences in tolerability among different amylin receptor agonists which are in different phases of clinical developments.