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: Thomas Thymann, Barbara Stoll, Lars Mecklenburg, Douglas G Burrin, Andreas Vegge, Niels Qvist, Thomas Eriksen, Palle B Jeppesen, Per T Sangild
• Journal: Journal of pediatric gastroenterology and nutrition (J Pediatr Gastroenterol Nutr) Vol. 58 Issue 6 Pg. 694-702 (Jun 2014) ISSN: 1536-4801 [Electronic] United States
• PMID: 24399211 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ALX-0600
• Gastrointestinal Agents
• Glucagon-Like Peptide 2
• Glucagon-Like Peptide-2 Receptor
• Peptides
• Receptors, Glucagon
• teduglutide

Topics

• Adaptation, Physiological (drug effects)
• Animals
• Body Weight (drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Female
• Gastrointestinal Agents (pharmacology, therapeutic use)
• Glucagon-Like Peptide 2 (pharmacology, therapeutic use)
• Glucagon-Like Peptide-2 Receptor
• Growth (drug effects)
• Intestine, Small (drug effects, growth & development, metabolism)
• Jejunostomy
• Organ Size (drug effects)
• Parenteral Nutrition, Total
• Peptides (pharmacology, therapeutic use)
• Protein Biosynthesis (drug effects)
• Receptors, Glucagon (metabolism)
• Short Bowel Syndrome (drug therapy, metabolism)
• Swine