Amylin in the Periphery II: An Updated Mini-Review

Amylin is a polypeptide that is cosecreted with insulin from the β cells of the pancreas. Therefore, in states of diabetes in which the β-cell mass is largely depleted or dysfunctional, insulin and amylin secretion are also lost or dysregulated.While the soluble monomeric form of amylin acts as a hormone that alters physiological responses related to feeding and acts as a specific growth factor, there has been renewed interest in the less-soluble oligomeric and insoluble polymeric forms of human (also monkey and cat) amylin that may contribute to the establishment of a pathophysiological pathway to overt diabetes. With this discovery has grown the hope of minimizing, with appropriate therapy, these toxic forms to preserve the functional β-cell mass. Human β cells may also be more vulnerable to these forms and one risk factor, a higher fat diet, may promote toxic forms. The generation and utilities of transgenic rodent models, which express enhanced levels of human amylin, have been accompanied by strategies that may lead to the reduction of toxic forms and associated risk factors.The successful definition and faithful expression of the physiological receptors (and complexes) for amylin that may differ for each target organ is an important development in the field of amylin research generally. Besides the heuristic value for the understanding of the molecular biology of receptors, the opportunity to screen and identify nonpeptide analogues that bind the physiological receptors has important implications for biomedicine and clinical practice in relation to treatments for diabetic complications, bone diseases, and eating disorders. In particular, in their capacities to mimic the effects of amylin as a growth factor, amylin analogues may prove useful in the stimulation of β-cell mass (in conjunction with other factors), reduce the activity of the osteoclast population, and stimulate the regeneration of proximal tubules following toxic insult (and thus avoid the development of renal insufficiency).