title: Acute effects of the glucagon-like peptide 2 analogue, teduglutide, on intestinal adaptation in short bowel syndrome.
abstract: Neonatal short bowel syndrome following massive gut resection is associated with malabsorption of nutrients. The intestinotrophic factor glucagon-like peptide 2 (GLP-2) improves gut function in adult patients with short bowel syndrome, but its effect in pediatric patients remains unknown. Our objective was to test the efficacy of the long-acting synthetic human GLP-2 analogue, teduglutide (ALX-0600), in a neonatal piglet jejunostomy model. Two-day-old pigs were subjected to resection of 50% of the small intestine (distal part), and the remnant intestine was exteriorized on the abdominal wall as a jejunostomy. All pigs were given total parenteral nutrition for 7 days and a single daily injection of the following doses of teduglutide: 0.01 (n = 6), 0.02 (n = 6), 0.1 (n = 5), or 0.2 mg · kg · day (n = 6), and compared with placebo (n = 9). Body weight increment was similar for all 4 teduglutide groups but higher than placebo (P < 0.05). There was a dose-dependent increase in weight per length of the remnant intestine (P < 0.01) and fractional protein synthesis rate in the intestine was increased in the 0.2 mg · kg · day group versus placebo (P < 0.001); however, functional and structural endpoints including activity of digestive enzymes, absorption of enteral nutrients, and immunohistochemistry (Ki67, villin, FABP2, ChgA, and GLP-2R) were not affected by the treatment. Teduglutide induces trophicity on the remnant intestine but has limited acute effects on functional endpoints. Significant effects of teduglutide on gut function may require a longer adaptation period and/or a more frequent administration of the peptide. In perspective, GLP-2 or its analogues may be relevant to improve intestinal adaptation in pediatric patients with short bowel syndrome.
authors.affiliation: *Department of Nutrition, Exercise, and Sports, University of Copenhagen, Frederiksberg C, Denmark †Childrens Nutrition Research Center, Baylor College of Medicine, Houston, TX ‡Takeda GmbH, Konstanz, Germany §Department of Surgery, Gastroenterology, Pediatrics and Endocrinology, Odense University Hospital, Odense C ||Department of Small Animal Clinical Sciences, University of Copenhagen, Frederiksberg C ¶Department of Gastroenterology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Thymann
authors.forename: Barbara
authors.initials: B
authors.lastname: Stoll
authors.forename: Lars
authors.initials: L
authors.lastname: Mecklenburg
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Burrin
authors.forename: Andreas
authors.initials: A
authors.lastname: Vegge
authors.forename: Niels
authors.initials: N
authors.lastname: Qvist
authors.forename: Thomas
authors.initials: T
authors.lastname: Eriksen
authors.forename: Palle B
authors.initials: PB
authors.lastname: Jeppesen
authors.forename: Per T
authors.initials: PT
authors.lastname: Sangild
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology / Q000627:therapeutic use*; D000067758:Glucagon-Like Peptide-2 Receptor; D006128:Growth / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D007582:Jejunostomy; D009929:Organ Size / Q000187:drug effects; D010289:Parenteral Nutrition, Total; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D014176:Protein Biosynthesis / Q000187:drug effects; D018027:Receptors, Glucagon / Q000378:metabolism*; D012778:Short Bowel Syndrome / Q000188:drug therapy* / Q000378:metabolism; D013552:Swine
chemical_list: C438272:ALX-0600; D005765:Gastrointestinal Agents; D053767:Glucagon-Like Peptide 2; D000067758:Glucagon-Like Peptide-2 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; C494910:teduglutide