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Novel Long-Acting GLP-2 Analogue, FE 203799 (Apraglutide), Enhances Adaptation and Linear Intestinal Growth in a Neonatal Piglet Model of Short Bowel Syndrome with Total Resection of the Ileum

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Enteral Autonomy and Days Off Parenteral Support With Teduglutide Treatment for Short Bowel Syndrome in the STEPS Trials

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Repeated Metabolic Balance Studies in Patients With Short Bowel Syndrome

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Impact of Teduglutide on Quality of Life Among Patients With Short Bowel Syndrome and Intestinal Failure

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Colon polyps in patients with short bowel syndrome before and after teduglutide: Post hoc analysis of the STEPS study series

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Enteral Autonomy and Days Off Parenteral Support With Teduglutide Treatment for Short Bowel Syndrome in the STEPS Trials

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Repeated Metabolic Balance Studies in Patients With Short Bowel Syndrome

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Impact of Teduglutide on Quality of Life Among Patients With Short Bowel Syndrome and Intestinal Failure

    Research output: Contribution to journalJournal articleResearchpeer-review

  • George M Slim
  • Marihan Lansing
  • Pamela Wizzard
  • Patrick N Nation
  • Sarah E Wheeler
  • Patricia L Brubaker
  • Palle B Jeppesen
  • Paul W Wales
  • Justine M Turner
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BACKGROUND: Glucagon-like peptide-2 (GLP-2) is an intestinotrophic factor released from L-cells in the ileum, a segment commonly resected or atretic in neonatal short bowel syndrome (SBS). In piglets, ileal resection decreases intestinal adaptation and endogenous GLP-2 production, whereas exogenous replacement promotes adaptation. In this study, we determined the effect of a novel long-acting GLP-2 analogue, FE 203799 (FE; apraglutide), upon intestinal growth, adaptation, and function in neonatal SBS piglets without ileum.

METHODS: Neonatal piglets were randomized to saline (n = 10) vs FE treatment (n = 8). All piglets underwent 75% intestinal resection with jejunocolic anastomosis and were pair-fed parenteral and enteral nutrition. Saline and FE (5 mg/kg) treatments were administered subcutaneously on days 0 and 4. On day 6, 24-hour fecal samples were collected for subsequent nutrient analysis. On day 7, small-intestinal length and weight were measured and tissue collected for analyses.

RESULTS: On day 7, saline and FE-treated piglets were healthy and gained equivalent weight (P = 0.12). Compared with saline piglets, FE-treated piglets had lower fecal fat (P = 0.043) and energy (P = 0.043) losses and exhibited intestinal lengthening (P = 0.001), greater small-intestinal weight (P = 0.004), longer villus height (P = 0.027), and greater crypt depth (P = 0.054).

CONCLUSIONS: The subcutaneous GLP-2 analogue, FE, enhanced intestinal adaptation in a neonatal model of SBS without ileum. The observed intestinal lengthening with FE treatment was unique compared with our prior experience with native GLP-2 in this same model and has important clinical implications for treating neonatal SBS. At this developmental stage, growth in the intestine, if augmented, could accelerate weaning from parenteral nutrition.

Original languageEnglish
JournalJournal of Parenteral and Enteral Nutrition
Volume43
Issue number7
Pages (from-to)891-898
Number of pages8
ISSN0148-6071
DOIs
Publication statusPublished - 2019

ID: 59434754