Acute effects of the glucagon-like peptide 2 analogue, teduglutide, on intestinal adaptation in short bowel syndrome.
J Pediatr Gastroenterol Nutr
; 58(6): 694-702, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24399211
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 (nâ=â6), 0.02 (nâ=â6), 0.1 (nâ=â5), or 0.2 mg · kg · day (nâ=â6), and compared with placebo (nâ=â9). Body weight increment was similar for all 4 teduglutide groups but higher than placebo (Pâ<â0.05). There was a dose-dependent increase in weight per length of the remnant intestine (Pâ<â0.01) and fractional protein synthesis rate in the intestine was increased in the 0.2 mg · kg · day group versus placebo (Pâ<â0.001); 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Síndrome do Intestino Curto
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Fármacos Gastrointestinais
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Adaptação Fisiológica
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Receptores de Glucagon
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Peptídeo 2 Semelhante ao Glucagon
/
Intestino Delgado
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Pediatr Gastroenterol Nutr
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Dinamarca