Acute effects of the Glucagon-Like Peptide 2 analogue, teduglutide, on intestinal adaptation in newborn pigs with short bowel syndrome

TY - JOUR

T1 - Acute effects of the Glucagon-Like Peptide 2 analogue, teduglutide, on intestinal adaptation in newborn pigs with short bowel syndrome

AU - Thymann, Thomas

AU - Stoll, Barbara

AU - Mecklenburg, Lars

AU - Burrin, Douglas G

AU - Vegge, Andreas

AU - Qvist, Niels

AU - Eriksen, Thomas

AU - Jeppesen, Palle Bekker

AU - Sangild, Per Torp

N1 - CURIS 2014 NEXS 063

PY - 2014/6

Y1 - 2014/6

N2 - 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-1 kg-1 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 -1 day-1 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.

AB - 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-1 kg-1 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 -1 day-1 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.

U2 - 10.1097/MPG.0000000000000295

DO - 10.1097/MPG.0000000000000295

M3 - Journal article

C2 - 24399211

SN - 0277-2116

VL - 58

SP - 694

EP - 702

JO - Journal of Pediatric Gastroenterology and Nutrition

JF - Journal of Pediatric Gastroenterology and Nutrition

IS - 6

ER -