Chaperones ameliorate beta cell dysfunction and amyloid formation associated with islet amyloid polypeptide overexpression

In type 2 diabetes and islet transplantation beta-cell dysfunction is thought to be due to several causes, one being the formation of toxic protein aggregates called islet amyloid, formed by accumulations of misfolded human islet amyloid polypeptide (hIAPP). The process of hIAPP misfolding and aggregation is one of the factors that may perturb the endoplasmic reticulum (ER) homeostasis, leading to beta cell dysfunction and ultimately, cell death. Molecular chaperones have been described to be important for regulation of ER response to ER stress by stabilizing protein conformation and improving ER capacity. The aim of the present work is to determine whether chaperone treatment is able to counteract hIAPP-induced beta cell dysfunction and, ultimately, diminish amyloid formation and cell death in pancreatic islets.