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Synergy of glucagon-like peptide-2 and epidermal growth factor coadministration on intestinal adaptation in neonatal piglets with short bowel syndrome.
- Source :
-
American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2017 Apr 01; Vol. 312 (4), pp. G390-G404. Date of Electronic Publication: 2017 Jan 19. - Publication Year :
- 2017
-
Abstract
- Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) treatment enhance intestinal adaptation. To determine whether these growth factors exert synergistic effects on intestinal growth and function, GLP-2 and EGF-containing media (EGF-cm) were administered, alone and in combination, in neonatal piglet models of short bowel syndrome (SBS). Neonatal Landrace-Large White piglets were block randomized to 75% midintestinal [jejunoileal (JI) group] or distal intestinal [jejunocolic (JC) group] resection or sham control, with 7-day infusion of saline (control), intravenous human GLP-2 (11 nmol·kg <superscript>-1</superscript> ·day <superscript>-1</superscript> ) alone, enteral EGF-cm (80 μg·kg <superscript>-1</superscript> ·day <superscript>-1</superscript> ) alone, or GLP-2 and EGF-cm in combination. Adaptation was assessed by intestinal length, histopathology, Üssing chamber analysis, and real-time quantitative PCR of intestinal growth factors. Combined EGF-cm and GLP-2 treatment increased intestinal length in all three surgical models ( P < 0.01). EGF-cm alone selectively increased bowel weight per length and jejunal villus height in the JI group only. The JC group demonstrated increased intestinal weight and villus height ( P < 0.01) when given either GLP-2 alone or in combination with EGF-cm, with no effect of EGF-cm alone. Jejunal permeability of mannitol and polyethylene glycol decreased with combination therapy in both SBS groups ( P < 0.05). No difference was observed in fat absorption or body weight gain. IGF-1 mRNA was differentially expressed in JI vs. JC piglets with treatment. Combined treatment with GLP-2 and EGF-cm induced intestinal lengthening and decreased permeability, in addition to the trophic effects of GLP-2 alone. Our findings demonstrate the benefits of novel combination GLP-2 and EGF treatment for neonatal SBS, especially in the JC model representing most human infants with SBS. NEW & NOTEWORTHY Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) are intestinotrophic, with demonstrated benefit in both animal models and human studies of short bowel syndrome (SBS). The current research shows that over and above known trophic effects, the combination of GLP-2 and EGF synergistically lengthens the bowel in neonatal piglet models of SBS. Most notable benefit occurred with resection of the terminal ileum, the common clinical anatomy seen in neonatal SBS and associated with least de novo lengthening postsurgery.<br /> (Copyright © 2017 the American Physiological Society.)
- Subjects :
- Animals
Animals, Newborn
Disease Models, Animal
Drug Synergism
Epidermal Growth Factor therapeutic use
Glucagon-Like Peptide 2 therapeutic use
Intestinal Mucosa drug effects
Intestines pathology
Male
Organ Size drug effects
Short Bowel Syndrome pathology
Swine
Treatment Outcome
Adaptation, Physiological drug effects
Epidermal Growth Factor pharmacology
Glucagon-Like Peptide 2 pharmacology
Intestines drug effects
Short Bowel Syndrome drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1547
- Volume :
- 312
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Gastrointestinal and liver physiology
- Publication Type :
- Academic Journal
- Accession number :
- 28104586
- Full Text :
- https://doi.org/10.1152/ajpgi.00281.2016