GLP-2 delays but does not prevent the onset of necrotizing enterocolitis in preterm pigs.
OBJECTIVE
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.
USDA/ARS Children's Nutrition Research Center, the Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Houston, TX 77030, USA.
Nancy M
NM
Benight
Barbara
B
Stoll
Oluyinka O
OO
Olutoye
Jens J
JJ
Holst
Douglas G
DG
Burrin
D000818:Animals; D017849:Animals, Inbred Strains; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D002585:Cesarean Section; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000209:etiology / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D053767:Glucagon-Like Peptide 2 / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D007263:Infusions, Parenteral; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D007421:Intestine, Small / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D010289:Parenteral Nutrition, Total / Q000009:adverse effects; D011247:Pregnancy; D047928:Premature Birth / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011897:Random Allocation; D000685:Serum Amyloid A Protein / Q000032:analysis; D013781:Texas; D015854:Up-Regulation / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D053767:Glucagon-Like Peptide 2; D000685:Serum Amyloid A Protein