title: Effect of Roux-en-Y gastric bypass on the distribution and hormone expression of small-intestinal enteroendocrine cells in obese patients with type 2 diabetes.
abstract: OBJECTIVE
  We studied the impact of Roux-en-Y gastric bypass (RYGB) on the density and hormonal gene expression of small-intestinal enteroendocrine cells in obese patients with type 2 diabetes.
  
  
  METHODS
  Twelve patients with diabetes and 11 age- and BMI-matched controls underwent RYGB followed by enteroscopy ~10 months later. Mucosal biopsies taken during surgery and enteroscopy were immunohistochemically stained for glucagon-like peptide-1 (GLP-1), peptide YY (PYY), cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide (GIP) and prohormone convertase 2 (PC2) and the expression of GCG (encoding preproglucagon), PYY, CCK, GIP, GHRL (encoding ghrelin), SCT (encoding secretin), NTS (encoding neurotensin) and NR1H4 (encoding farnesoid X receptor) was evaluated.
  
  
  RESULTS
  The density of cells immunoreactive for GLP-1, CCK and GIP increased in patients after RYGB and the density of those immunoreactive for GLP-1, PYY, CCK and PC2 increased in controls. In both groups, GHRL, SCT and GIP mRNA was reduced after RYGB while PYY, CCK, NTS and NR1H4 gene expression was unaltered. GCG mRNA was upregulated in both groups.
  
  
  CONCLUSIONS
  Numerous alterations in the distribution of enteroendocrine cells and their expression of hormonal genes are seen after RYGB and include increased density of GLP-1-, PYY-, CCK-, GIP- and PC2-positive cells, reduced gene expression of GHRL, SCT and GIP and increased expression of GCG.
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900, Hellerup, Denmark.|NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.|Novo Nordisk Scandinavia AB, Copenhagen, Denmark.
authors.forename: Nicolai A
authors.initials: NA
authors.lastname: Rhee
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900, Hellerup, Denmark.
authors.forename: Camilla D
authors.initials: CD
authors.lastname: Wahlgren
authors.affiliation: NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Pedersen
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900, Hellerup, Denmark.
authors.forename: Brynjulf
authors.initials: B
authors.lastname: Mortensen
authors.affiliation: Unit of Enteroscopy, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: Ebbe
authors.initials: E
authors.lastname: Langholz
authors.affiliation: Unit of Enteroscopy, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: Erik P
authors.initials: EP
authors.lastname: Wandall
authors.affiliation: Unit of Enteroscopy, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: Steffen U
authors.initials: SU
authors.lastname: Friis
authors.affiliation: Unit of Enteroscopy, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.|Gastro Unit D, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Vilmann
authors.affiliation: Gubra Aps, Hørsholm, Denmark.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Paulsen
authors.affiliation: Gastro Unit, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.
authors.forename: Viggo B
authors.initials: VB
authors.lastname: Kristiansen
authors.affiliation: Gubra Aps, Hørsholm, Denmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Jelsing
authors.affiliation: Gubra Aps, Hørsholm, Denmark.
authors.forename: Louise S
authors.initials: LS
authors.lastname: Dalbøge
authors.affiliation: NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Steen S
authors.initials: SS
authors.lastname: Poulsen
authors.affiliation: NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900, Hellerup, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900, Hellerup, Denmark. filipknop@dadlnet.dk.|NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. filipknop@dadlnet.dk.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
mesh_terms: D000328:Adult; D002766:Cholecystokinin / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism / Q000601:surgery; D019858:Enteroendocrine Cells / Q000378:metabolism*; D005260:Female; D015390:Gastric Bypass; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism; D054439:Ghrelin / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000150:complications / Q000378:metabolism / Q000601:surgery*; D019894:Peptide YY / Q000378:metabolism; D045706:Proprotein Convertase 2 / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D054439:Ghrelin; D019894:Peptide YY; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin; D045706:Proprotein Convertase 2
keywords: Cholecystokinin; Enteroendocrine cells; Ghrelin; Glucagon-like peptide-1; Glucose-dependent insulinotropic polypeptide; Immunohistochemistry; Obesity; Peptide YY; Quantitative polymerase chain reaction; Roux-en-Y gastric bypass; Type 2 diabetes