title: Glucagon-Like Peptide 2 Improves Cholestasis in Parenteral Nutrition--Associated Liver Disease.
abstract: BACKGROUND
  Parenteral nutrition-associated liver disease (PNALD) remains a significant cause of morbidity and mortality in neonates with intestinal failure. Although glucagon-like peptide-2 (GLP-2) is being advanced as therapy, the effect of GLP-2 treatment on PNALD is unknown. We aim to investigate the effect of exogenous GLP-2 administration on hepatic function in a neonatal piglet model of PNALD.
  
  
  METHODS
  Neonatal piglets (aged 2-6 days) underwent jugular venous catheterization to receive isonitrogenous, isocaloric parenteral nutrition (PN). Piglets were allocated to 2 groups: group 1 (n = 8) received saline while group 2 (n = 7) received GLP-2 (at 11 nmol/kg/d). After 17 days, piglets underwent terminal laparotomy, and bile flow was measured. Liver specimens were analyzed histologically and with immunoperoxidase staining. Age-matched sow-reared control piglets (group 3, n = 8) were used for comparison.
  
  
  RESULTS
  Both groups 1 and 2 receiving PN developed cholestasis relative to sow-reared controls, as evidenced by a decrease in bile flow and increase in serum total bilirubin. However, group 2 had improved bile flow (1.35 vs 0.73 µL/g; P = .02) and diminished bilirubin (38.0 vs 78.5 µmol/L; P = .008) compared with group 1. Group 2 also had lower serum alanine aminotransferase levels, a marker of liver injury. Histologically, the liver specimens in group 1 had marked hepatocyte pigmentation, which was decreased in group 2 specimens.
  
  
  CONCLUSIONS
  The exogenous administration of GLP-2 is associated with the improvement of cholestasis and liver injury. This study introduces a novel role for GLP-2 in improving PNALD in the setting of prolonged PN duration.
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: David W
authors.initials: DW
authors.lastname: Lim
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada Department of Surgery, Hospital for Sick Children & University of Toronto, Toronto, Ontario, Canada.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Wales
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Josephson
authors.affiliation: Department of Laboratory Medicine & Pathology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Patrick N
authors.initials: PN
authors.lastname: Nation
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Wizzard
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada Department of Laboratory Medicine & Pathology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Consolato M
authors.initials: CM
authors.lastname: Sergi
authors.affiliation: Department of Agricultural Food & Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Field
authors.affiliation: Department of Surgery, University of Calgary, Calgary, Alberta, Canada.
authors.forename: David L
authors.initials: DL
authors.lastname: Sigalet
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada Department of Agricultural Food & Nutritional Science, University of Alberta, Edmonton, Alberta, Canada Justine.Turner@albertahealthservices.ca.
authors.forename: Justine M
authors.initials: JM
authors.lastname: Turner
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D001663:Bilirubin / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002779:Cholestasis / Q000150:complications / Q000188:drug therapy*; D005260:Female; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008107:Liver Diseases / Q000150:complications / Q000188:drug therapy*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010288:Parenteral Nutrition / Q000009:adverse effects*; D013552:Swine
chemical_list: D053767:Glucagon-Like Peptide 2; D002097:C-Reactive Protein; D000410:Alanine Transaminase; D001663:Bilirubin
keywords: cholestasis; glucagon-like peptide 2; intestinal failure; neonate; parenteral nutrition; parenteral nutrition associated liver disease