Toxic Human Islet Amyloid Polypeptide (h-IAPP) Oligomers Are Intracellular, and Vaccination to Induce Anti-Toxic Oligomer Antibodies Does Not Prevent h-IAPP–Induced -Cell Apoptosis in h-IAPP Transgenic Mice

OBJECTIVE—Islets in type 2 diabetes are characterized by a deficit in -cells, increased -cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). The toxic form of amyloidogenic protein oligomers are distinct and smaller than amyloid fibrils and act by disrupting membranes. Using antibodies that bind to toxic IAPP oligomers (but not IAPP monomers or fibrils) and a vaccination-based approach, we sought to establish whether IAPP toxic oligomers form intraor extracellularly and whether vaccination to induce anti-toxic oligomer antibodies prevents IAPP-induced apoptosis in human IAPP (h-IAPP) transgenic mice.