Islet amyloid and type 2 diabetes: overproduction or inadequate clearance and detoxification?

Abstract

A hallmark of type 2 diabetes is the reduction of pancreatic islet β cell mass through induction of apoptosis and lack of regeneration. In most patients, β cell dysfunction is associated with the presence of extracellular amyloid plaques adjacent to β cells and intracellular toxic oligomers that are comprised of islet amyloid polypeptide (IAPP). In this issue of the JCI, three independent research groups reveal that a functional autophagy system normally prevents the accumulation of toxic IAPP oligomers in human IAPP-expressing murine models. Furthermore, mice expressing human IAPP but deficient for β cell autophagy through genetic deletion of the autophagy initiator ATG7 developed β cell apoptosis and overt diabetes. Together, these studies indicate that autophagy protects β cells from the accumulation of toxic IAPP oligomers and suggest that enhancing autophagy may be a novel target for prevention of type 2 diabetes.