title: 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.
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Gupta
authors.forename: Jack L
authors.initials: JL
authors.lastname: Leahy
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology* / Q000502:physiology*; D058228:Islet Amyloid Polypeptide / Q000378:metabolism* / Q000502:physiology*; D008297:Male
chemical_list: D058228:Islet Amyloid Polypeptide