title: Pancreatic polypeptide regulates glucagon release through PPYR1 receptors expressed in mouse and human alpha-cells.
abstract: BACKGROUND
  Plasma levels of pancreatic polypeptide (PP) rise upon food intake. Although other pancreatic islet hormones, such as insulin and glucagon, have been extensively investigated, PP secretion and actions are still poorly understood.
  
  
  METHODS
  The release of PP upon glucose stimulation and the effects of PP on glucagon and insulin secretion were analyzed in isolated pancreatic islets. Expression of PP receptor (PPYR1) was investigated by immunoblotting, quantitative RT-PCR on sorted pancreatic islet cells, and immunohistochemistry.
  
  
  RESULTS
  In isolated mouse pancreatic islets, glucose stimulation increased PP release, while insulin secretion was up and glucagon release was down. Direct exposure of islets to PP inhibited glucagon release. In mouse islets, PPYR1 protein was observed by immunoblotting and quantitative RT-PCR revealed PPYR1 expression in the FACS-enriched glucagon alpha-cell fraction. Immunohistochemistry on pancreatic sections showed the presence of PPYR1 in alpha-cells of both mouse and human islets, while the receptor was absent in other islet cell types and exocrine pancreas.
  
  
  CONCLUSIONS
  Glucose stimulates PP secretion and PP inhibits glucagon release in mouse pancreatic islets. PP receptors are present in alpha-cells of mouse and human pancreatic islets.
  
  
  CONCLUSIONS
  These data demonstrate glucose-regulated secretion of PP and its effects on glucagon release through PPYR1 receptors expressed by alpha-cells.
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona (PRBB), Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Aragón
authors.affiliation: Department of Cell Physiology and Metabolism, Geneva University Medical Center, Geneva, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Karaca
authors.affiliation: Diabetes Research Laboratory. IDIBAPS (Institut Investigacions Biomèdiques August Pi i Sunyer), CIBERDEM, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Novials
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona (PRBB), Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Maldonado
authors.affiliation: Department of Cell Physiology and Metabolism, Geneva University Medical Center, Geneva, Switzerland. Electronic address: Pierre.Maechler@unige.ch.
authors.forename: P
authors.initials: P
authors.lastname: Maechler
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona (PRBB), Barcelona, Spain. Electronic address: rubiweiss@gmail.com.
authors.forename: B
authors.initials: B
authors.lastname: Rubí
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005934:Glucagon / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D010191:Pancreatic Polypeptide / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000096:biosynthesis*; D013549:Sweetening Agents / Q000494:pharmacology
chemical_list: D017476:Receptors, Neuropeptide Y; D013549:Sweetening Agents; C109491:neuropeptide Y4 receptor; D010191:Pancreatic Polypeptide; D005934:Glucagon; D005947:Glucose
keywords: Glucagon secretion; Glucose; Islets; PPYR1; Pancreatic polypeptide; Y4