title: Amyloid inhibitors enhance survival of cultured human islets.
abstract: BACKGROUND
  Amyloid fibrils created by misfolding and aggregation of proteins are a major pathological feature in a variety of degenerative diseases. Therapeutic approaches including amyloid vaccines and anti-aggregation compounds in models of amyloidosis point to an important role for amyloid in disease pathogenesis. Amyloid deposits derived from the beta-cell peptide islet amyloid polypeptide (IAPP or amylin) are a characteristic of type 2 diabetes and may contribute to loss of beta-cells in this disease.
  
  
  METHODS
  We developed a cellular model of rapid amyloid deposition using cultured human islets and observed a correlation between fibril accumulation and beta-cell death. A series of overlapping peptides derived from IAPP was generated.
  
  
  RESULTS
  A potent inhibitor (ANFLVH) of human IAPP aggregation was identified. This inhibitory peptide prevented IAPP fibril formation in vitro and in human islet cultures leading to a striking increase in islet cell viability.
  
  
  CONCLUSIONS
  These findings indicate an important contribution of IAPP aggregation to beta-cell death in situ and point to therapeutic applications for inhibitors of IAPP aggregation in enhancing beta-cell survival.
  
  
  CONCLUSIONS
  Anti-amyloid compounds could potentially reduce the loss of beta-cell mass in type 2 diabetes and maintain healthy human islet cultures for beta-cell replacement therapies.
authors.affiliation: Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Potter
authors.forename: Louise A
authors.initials: LA
authors.lastname: Scrocchi
authors.forename: Garth L
authors.initials: GL
authors.lastname: Warnock
authors.forename: Ziliang
authors.initials: Z
authors.lastname: Ao
authors.forename: Marika A
authors.initials: MA
authors.lastname: Younker
authors.forename: Lawrence
authors.initials: L
authors.lastname: Rosenberg
authors.forename: Mark
authors.initials: M
authors.lastname: Lipsett
authors.forename: C Bruce
authors.initials: CB
authors.lastname: Verchere
authors.forename: Paul E
authors.initials: PE
authors.lastname: Fraser
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000502:physiology / Q000648:ultrastructure; D008969:Molecular Sequence Data
chemical_list: D000682:Amyloid; D058228:Islet Amyloid Polypeptide