title: Selective ablation of peptide YY cells in adult mice reveals their role in beta cell survival.
abstract: OBJECTIVE
  In the pancreas, peptide YY (PYY) is expressed by a subpopulation of nonbeta cells in the islets of Langerhans. We investigated the function of these cells in the pancreas of adult mice.
  
  
  METHODS
  We generated mice in which administration of diphtheria toxin (DT) led to specific ablation of PYY-expressing cells. We investigated the effects of loss of PYY cells on glucose homeostasis.
  
  
  RESULTS
  Loss of PYY cells in adult mice resulted in severe hyperglycemia, which was associated with significant loss of pancreatic insulin and disruption of islet morphology. In vitro administration of DT to isolated islets significantly reduced numbers of PYY-expressing cells and levels of insulin. Administration of either pancreatic polypeptide (a strong agonist of the receptor Y(4)) or PYY(3-36) (a selective agonist of the receptor Y(2)) did not restore loss of pancreatic insulin following administration of DT. However, a long-acting PYY analogue reduced the loss of insulin, and administration of this analogue reduced the hyperglycemia and insulin loss induced by streptozotocin in mice.
  
  
  CONCLUSIONS
  PYY appears to regulate beta cell function and survival via the receptor Y(1/2). These findings might be developed to treat and prevent loss of beta cells in patients with diabetes mellitus.
authors.affiliation: Imperial College, London, England.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Sam
authors.forename: David J
authors.initials: DJ
authors.lastname: Gunner
authors.forename: Aileen
authors.initials: A
authors.lastname: King
authors.forename: Shanta J
authors.initials: SJ
authors.lastname: Persaud
authors.forename: Lucy
authors.initials: L
authors.lastname: Brooks
authors.forename: Klara
authors.initials: K
authors.lastname: Hostomska
authors.forename: Heather E
authors.initials: HE
authors.lastname: Ford
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
authors.forename: Gavin A
authors.initials: GA
authors.lastname: Bewick
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival; D004167:Diphtheria Toxin; D006943:Hyperglycemia / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000502:physiology; D007515:Islets of Langerhans / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010191:Pancreatic Polypeptide / Q000378:metabolism; D010446:Peptide Fragments; D019894:Peptide YY / Q000172:deficiency / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D004167:Diphtheria Toxin; D007328:Insulin; D010446:Peptide Fragments; D019894:Peptide YY; C061785:peptide YY (3-36); D010191:Pancreatic Polypeptide