Factors That Contribute to hIAPP Amyloidosis in Type 2 Diabetes Mellitus

Abstract

Cases of Type 2 Diabetes Mellitus (T2DM) are increasing at an alarming rate due to the rise in obesity, sedentary lifestyles, glucose-rich diets and other factors. Numerous studies have increasingly illustrated the pivotal role that human islet amyloid polypeptide (hIAPP) plays in the pathology of T2DM through damage and subsequent loss of pancreatic β-cell mass. HIAPP can misfold and form amyloid fibrils which are preceded by pre-fibrillar oligomers and monomers, all of which have been linked, to a certain extent, to β-cell cytotoxicity through a range of proposed mechanisms. This review provides an up-to-date summary of recent progress in the field, highlighting factors that contribute to hIAPP misfolding and aggregation such as hIAPP protein concentration, cell stress, molecular chaperones, the immune system response and cross-seeding with other amyloidogenic proteins. Understanding the structure of hIAPP and how these factors affect amyloid formation will help us better understand how hIAPP misfolds and aggregates and, importantly, help identify potential therapeutic targets for inhibiting amyloidosis so alternate and more effective treatments for T2DM can be developed.