Tags

Type your tag names separated by a space and hit enter

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.
JPEN J Parenter Enteral Nutr. 2019 09; 43(7):891-898.JJ

Abstract

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.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Slim GM
Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Lansing M
Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Wizzard P
Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Nation PN
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
Wheeler SE
Departments of Physiology and Medicine, University of Toronto, Toronto, Ontario, Canada.
Brubaker PL
Departments of Physiology and Medicine, University of Toronto, Toronto, Ontario, Canada.
Jeppesen PB
Department of Medical Gastroenterology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Wales PW
Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada. Division of General Surgery, Hospital for Sick Children, Toronto, Ontario, Canada. Group for Improvement of Intestinal Function and Treatment, Hospital for Sick Children, Toronto, Ontario, Canada.
Turner JM
Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.

MeSH

Adaptation, PhysiologicalAnimalsAnimals, NewbornDisease Models, AnimalEnteral NutritionGlucagon-Like Peptide 2HumansIleumInfant, NewbornIntestine, SmallParenteral NutritionPeptidesShort Bowel SyndromeSwine

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30614011

Citation

Slim, George M., et al. "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." JPEN. Journal of Parenteral and Enteral Nutrition, vol. 43, no. 7, 2019, pp. 891-898.
Slim GM, Lansing M, Wizzard P, et al. 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. JPEN J Parenter Enteral Nutr. 2019;43(7):891-898.
Slim, G. M., Lansing, M., Wizzard, P., Nation, P. N., Wheeler, S. E., Brubaker, P. L., Jeppesen, P. B., Wales, P. W., & Turner, J. M. (2019). 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. JPEN. Journal of Parenteral and Enteral Nutrition, 43(7), 891-898. https://doi.org/10.1002/jpen.1500
Slim GM, et al. 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. JPEN J Parenter Enteral Nutr. 2019;43(7):891-898. PubMed PMID: 30614011.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Slim,George M, AU - Lansing,Marihan, AU - Wizzard,Pamela, AU - Nation,Patrick N, AU - Wheeler,Sarah E, AU - Brubaker,Patricia L, AU - Jeppesen,Palle B, AU - Wales,Paul W, AU - Turner,Justine M, Y1 - 2019/01/06/ PY - 2018/10/25/received PY - 2018/12/10/accepted PY - 2019/1/8/pubmed PY - 2020/11/3/medline PY - 2019/1/8/entrez SP - 891 EP - 898 JF - JPEN. Journal of parenteral and enteral nutrition JO - JPEN J Parenter Enteral Nutr VL - 43 IS - 7 N2 - 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. SN - 1941-2444 UR - https://www.unboundmedicine.com/medline/citation/30614011/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_ DB - PRIME DP - Unbound Medicine ER -