GLP‐2 Delays but Does Not Prevent the Onset of Necrotizing Enterocolitis in Preterm Pigs

• Published in: Journal of pediatric gastroenterology and nutrition Vol. 56; no. 6; pp. 623 - 630
• Main Authors: Benight, Nancy M., Stoll, Barbara, Olutoye, Oluyinka O., Holst, Jens J., Burrin, Douglas G.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Copyright by ESPGHAN and NASPGHAN 01.06.2013; Lippincott Williams & Wilkins
• Subjects: Animals; Animals, Inbred Strains; Animals, Newborn; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - metabolism; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biological and medical sciences; Cesarean Section; Disease Models, Animal; Diseases of mother, fetus and pregnancy; Enterocolitis, Necrotizing - etiology; Enterocolitis, Necrotizing - immunology; Enterocolitis, Necrotizing - physiopathology; Enterocolitis, Necrotizing - prevention & control; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Glucagon-Like Peptide 2 - administration & dosage; Glucagon-Like Peptide 2 - adverse effects; Glucagon-Like Peptide 2 - metabolism; Glucagon-Like Peptide 2 - therapeutic use; Gynecology. Andrology. Obstetrics; Humans; inflammation; Infusions, Parenteral; Intestinal Mucosa - drug effects; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestinal Mucosa - ultrastructure; Intestine, Small - drug effects; Intestine, Small - immunology; Intestine, Small - metabolism; Intestine, Small - ultrastructure; Male; Medical sciences; Microvilli - drug effects; Microvilli - immunology; Microvilli - metabolism; Microvilli - ultrastructure; neonate; Other diseases. Semiology; Parenteral Nutrition, Total - adverse effects; Pregnancy; Pregnancy. Fetus. Placenta; Premature Birth - drug therapy; Premature Birth - metabolism; Premature Birth - pathology; Premature Birth - physiopathology; Random Allocation; serum amyloid A; Serum Amyloid A Protein - analysis; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Texas; Up-Regulation - drug effects; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Texas; Human; Premature; Necrotizing enterocolitis; Metabolic diseases; Glucagon-like peptide II; Pig; Prevention; Vertebrata; Mammalia; Newborn; Prematurity; Animal; Gastroenterology; Digestive diseases; Intestinal disease; Artiodactyla; Ungulata
• ISSN: 0277-2116; 1536-4801
• DOI: 10.1097/MPG.0b013e318286891e

ABSTRACT Objectives: Necrotizing enterocolitis (NEC) is complex disease thought to occur as a result of an immaturity of the gastrointestinal tract of preterm infants. Intestinal dysfunction induced by total parental nutrition (TPN) may increase the risk for NEC upon introduction of enteral feeding. We hypothesized that the intestinal trophic and anti‐inflammatory actions previously ascribed to the gut hormone, glucagon‐like peptide‐2 (GLP‐2), would reduce the incidence of NEC when given in combination with TPN in preterm piglets. Methods: Preterm, newborn piglets were nourished by TPN and infused continuously with either human GLP‐2 (100 μg · kg−1 · day−1) or control saline for 2 days (n = 12/group). On day 3, TPN was discontinued and pigs were given orogastric formula feeding every 3 hours, and continued GLP‐2 or control treatment until the onset of clinical signs of NEC for an additional 96 hours and tissue was collected for molecular and histological endpoints. Results: GLP‐2 treatment delayed the onset of NEC but was unable to prevent a high NEC incidence (∼70%) and severity that occurred in both groups. GLP‐2–treated pigs had less histological injury and increased proximal intestinal weight and mucosal villus height, but not crypt depth or Ki‐67–positive cells. Inflammatory markers of intestinal myeloperoxidase were unchanged and serum amyloid A levels were higher in GLP‐2–treated pigs. Conclusions: GLP‐2 did not prevent NEC and a proinflammatory response despite some reduction in mucosal injury and increased trophic effect.