title: GLP-2 administration results in increased proliferation but paradoxically an adverse outcome in a juvenile piglet model of short bowel syndrome.
abstract: OBJECTIVE
  The objective of the present study was to examine the effect of glucagon-like peptide-2 (GLP-2) administration in a piglet, juvenile model of short bowel syndrome.
  
  
  METHODS
  Four-week-old piglets underwent either a sham operation or 75% small bowel resection. Postoperatively, piglets received either polymeric infant formula diet or the diet and subcutaneous human recombinant GLP-2 (1600 microg/day for 7 days, 800 microg/day thereafter). Food intake was monitored throughout the experiment, and stool and serum samples obtained fortnightly. After the piglets were killed, tissues were obtained from the duodenum, jejunum, ileum, and terminal ileum, and used for morphological and functional analysis.
  
  
  RESULTS
  Treatment with GLP-2 resulted in significantly increased numbers of proliferating and apoptotic cells in the ileum of sham and small bowel resection piglets (P < 0.05). GLP-2 administration resulted in decreased weight gain, serum albumin, and disaccharidases in both sham and small bowel resection piglets (P < 0.001 compared with polymeric infant formula diet alone).
  
  
  CONCLUSIONS
  This is the first study to our knowledge to examine the effect of GLP-2 administration in a juvenile short bowel syndrome model. Contrary to adult rodent studies, administration of GLP-2 resulted in adverse outcomes including reduced ability to gain weight; decreased serum albumin, tissue maltase, and sucrase; and villous atrophy. We anticipate this information will have important implications for future paediatric clinical trials.
authors.affiliation: Intestinal Failure and Clinical Nutrition Group, Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia. prue.pereira@mcri.edu.au
authors.forename: Prue M
authors.initials: PM
authors.lastname: Pereira-Fantini
authors.forename: Eva S
authors.initials: ES
authors.lastname: Nagy
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Thomas
authors.forename: Russell G
authors.initials: RG
authors.lastname: Taylor
authors.forename: Magdy
authors.initials: M
authors.lastname: Sourial
authors.forename: Monique C J
authors.initials: MC
authors.lastname: Paris
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Fuller
authors.forename: Julie E
authors.initials: JE
authors.lastname: Bines
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D053767:Glucagon-Like Peptide 2 / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood; D006801:Humans; D007421:Intestine, Small / Q000201:enzymology / Q000473:pathology; D011994:Recombinant Proteins / Q000008:administration & dosage; D012709:Serum Albumin / Q000032:analysis; D012778:Short Bowel Syndrome / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D013393:Sucrase / Q000032:analysis; D013552:Swine; D015430:Weight Gain / Q000187:drug effects; D000520:alpha-Glucosidases / Q000032:analysis
chemical_list: D053767:Glucagon-Like Peptide 2; D011994:Recombinant Proteins; D012709:Serum Albumin; D000520:alpha-Glucosidases; D013393:Sucrase