title: GLP-1 Induces Barrier Protective Expression in Brunner's Glands and Regulates Colonic Inflammation.
abstract: Beneficial roles for glucagon-like peptide 1 (GLP-1)/GLP-1R signaling have recently been described in diseases, where low-grade inflammation is a common phenomenon. We investigated the effects of GLP-1 in Brunner's glands and duodenum with abundant expression of GLP-1 receptors, as well as GLP-1 effect on colonic inflammation.
  
  
  
  RNA from Brunner's glands of GLP-1R knockout and wild-type mice were subjected to full transcriptome profiling. Array results were validated by quantitative reverse transcription polymerase chain reaction in wild-type mice and compared with samples from inflammatory bowel disease (IBD) patients and controls. In addition, we performed a detailed investigation of the effects of exogenous liraglutide dosing in a T-cell driven adoptive transfer (AdTr) colitis mouse model.
  
  
  
  Analyses of the Brunner's gland transcriptomes of GLP-1R knockout and wild-type mice identified 722 differentially expressed genes. Upregulated transcripts after GLP-1 dosing included IL-33, chemokine ligand 20 (CCL20), and mucin 5b. Biopsies from IBD patients and controls, as well as data from the AdTr model, showed deregulated expression of GLP-1R, CCL20, and IL-33 in colon. Circulating levels of GLP-1 were found to be increased in mice with colitis. Finally, the colonic cytokine levels and disease scores of the AdTr model indicated reduced levels of colonic inflammation in liraglutide-dosed animals.
  
  
  
  We demonstrate that IL-33, GLP-1R, and CCL20 are deregulated in human IBD, and that prophylactic treatment with 0.6 mg/kg liraglutide improves disease in AdTr colitis. In addition, GLP-1 receptor agonists upregulate IL-33, mucin 5b, and CCL20 in murine Brunner's glands. Taken together, our data indicate that GLP-1 receptor agonists affect gut homeostasis in both proximal and distal parts of the gut.
authors.affiliation: *Global Research, Novo Nordisk A/S, Måløv, Denmark; †Department of Pediatrics, Center for Non-coding RNA in Technology and Health, CPH-DIRECT, Herlev Hospital, Herlev, Denmark; ‡Research Group for Microbial Biotechnology and Biorefining, National Food Institute, Technical University of Denmark, Lyngby, Denmark; §Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; and ‖Department of Gastroenterology, North Zealand Hospital, University of Copenhagen, Capital Region, Frederikssund, Denmark.
authors.forename: Claus H
authors.initials: CH
authors.lastname: Bang-Berthelsen
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Holm
authors.forename: Charles
authors.initials: C
authors.lastname: Pyke
authors.forename: Lotte
authors.initials: L
authors.lastname: Simonsen
authors.forename: Rolf
authors.initials: R
authors.lastname: Søkilde
authors.forename: Flemming
authors.initials: F
authors.lastname: Pociot
authors.forename: R Scott
authors.initials: RS
authors.lastname: Heller
authors.forename: Lasse
authors.initials: L
authors.lastname: Folkersen
authors.forename: Peter H
authors.initials: PH
authors.lastname: Kvist
authors.forename: Malene
authors.initials: M
authors.lastname: Jackerott
authors.forename: Jan
authors.initials: J
authors.lastname: Fleckner
authors.forename: Mogens
authors.initials: M
authors.lastname: Vilién
authors.forename: Lotte B
authors.initials: LB
authors.lastname: Knudsen
authors.forename: Anders
authors.initials: A
authors.lastname: Heding
authors.forename: Klaus S
authors.initials: KS
authors.lastname: Frederiksen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002011:Brunner Glands / Q000378:metabolism*; D054418:Chemokine CCL20 / Q000378:metabolism; D003092:Colitis / Q000188:drug therapy / Q000473:pathology*; D003106:Colon / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D000067757:Glucagon-Like Peptide-1 Receptor / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000473:pathology*; D000067596:Interleukin-33 / Q000378:metabolism; D000069450:Liraglutide / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D055257:Mucin-5B / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D055815:Young Adult; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: C108355:CCL20 protein, human; C493447:CCL20 protein, mouse; D054418:Chemokine CCL20; C000593833:GLP1R protein, human; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D000067596:Interleukin-33; C524579:Muc5b protein, mouse; D055257:Mucin-5B; D012333:RNA, Messenger; D000069450:Liraglutide; D000097789:Glucagon-Like Peptide-1 Receptor Agonists