title: Metabolic stress, IAPP and islet amyloid.
abstract: Amyloid forms within pancreatic islets in type 2 diabetes from aggregates of the β-cell peptide islet amyloid polypeptide (IAPP). These aggregates are toxic to β-cells, inducing β-cell death and dysfunction, as well as inciting islet inflammation. The β-cell is subject to a number of other stressors, including insulin resistance and hyperglycaemia, that may contribute to amyloid formation by increasing IAPP production by the β-cell. β-Cell dysfunction, evident as impaired glucose-stimulated insulin secretion and defective prohormone processing and exacerbated by metabolic stress, is also a likely prerequisite for islet amyloid formation to occur in type 2 diabetes. Islet transplants in patients with type 1 diabetes face similar stressors, and are subject to rapid amyloid formation and impaired proinsulin processing associated with progressive loss of β-cell function and mass. Declining β-cell mass is predicted to increase metabolic demand on remaining β-cells, promoting a feed-forward cycle of β-cell decline.
authors.affiliation: Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Montane
authors.forename: A
authors.initials: A
authors.lastname: Klimek-Abercrombie
authors.forename: K J
authors.initials: KJ
authors.lastname: Potter
authors.forename: C
authors.initials: C
authors.lastname: Westwell-Roper
authors.forename: C
authors.initials: C
authors.lastname: Bruce Verchere
mesh_terms: D000818:Animals; D017209:Apoptosis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance; D058228:Islet Amyloid Polypeptide / Q000235:genetics / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D051381:Rats; D013312:Stress, Physiological / Q000235:genetics
chemical_list: D058228:Islet Amyloid Polypeptide