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Title: Glucagon-like peptide-2 induces rapid digestive adaptation following intestinal resection in preterm neonates

Author
item Vegge, Andreas - University Of Copenhagen
item Thymann, Thomas - University Of Copenhagen
item Lund, Pernille - University Of Copenhagen
item Stoll, Barbara - Children'S Nutrition Research Center (CNRC)
item Bering, Stine - University Of Copenhagen
item Hartmann, Bolette - University Of Copenhagen
item Jelsing, Jacob - Gubra
item Qvist, Niels - University Of Copenhagen
item Burrin, Douglas - Doug
item Jeppesen, Palle - Rigshospitalet - Copenhagen University Hospital
item Holst, Jens - University Of Copenhagen
item Sangild, Per - University Of Copenhagen

Submitted to: American Journal of Physiology - Gastrointestinal and Liver Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/6/2013
Publication Date: 6/13/2013
Citation: Vegge, A., Thymann, T., Lund, P., Stoll, B., Bering, S.B., Hartmann, B., Jelsing, J., Qvist, N., Burrin, D.G., Jeppesen, P.B., Holst, J.J., Sangild, P.T. 2013. Glucagon-like peptide-2 induces rapid digestive adaptation following intestinal resection in preterm neonates. American Journal of Physiology - Gastrointestinal and Liver Physiology. 305(4):G277-G285.

Interpretive Summary: Premature infants are at increased risk for intestinal diseases that require surgical removal of a major portion of the intestine. After surgery, some of these infants develop a condition called short bowel syndrome (SBS) that limits the ability to digest and absorb nutrition and leads to poor growth and development. A critical feature of the intestine healing and regrowth process after surgery is the production of a growth hormone by the remaining intestine called glucagon-like peptide 2 (GLP-2). Some infants do not heal properly and develop SBS because they do not produce enough GLP-2. We designed a study using premature piglets as a model of human preterm infants to test whether GLP-2 treatment could improve the intestinal growth and healing process in piglets that have SBS after surgical removal of 50% of the intestine. The results showed that GLP-2 treatment effectively increased growth of the remaining intestine as well as the capacity to digest and absorb nutrients. These findings are clinically relevant and are the first to demonstrate in a premature animal model that GLP-2 treatment is an effective therapy for infants with SBS.

Technical Abstract: Short bowel syndrome (SBS) is a frequent complication after intestinal resection in infants suffering from intestinal disease. We tested whether treatment with the intestinotrophic hormone glucagon-like peptide-2 (GLP-2) increases intestinal volume and function in the period immediately following intestinal resection in preterm pigs. Preterm pigs were fed enterally for 48 hours before undergoing resection of 50% of the small intestine and establishment of a jejunostomy. Following resection, pigs were maintained on total parenteral nutrition (TPN) without (SBS, "n" = 8) or with GLP-2 treatment (3.5 micog/kg body weight per hour, SBS+GLP-2, "n" = 7) and compared with a group of unresected preterm pigs (control, "n" = 5). After 5 days of TPN, all piglets were fed enterally for 24 hours, and a nutrient balance study was performed. Intestinal resection was associated with markedly reduced endogenous GLP-2 levels. GLP-2 increased the relative absorption of wet weight (46 vs. 22%), energy (79 vs. 64%), and all macronutrients (all parameters "P" < 0.05). These findings were supported by a 200% increase in sucrase and maltase activities, a 50% increase in small intestinal epithelial volume ("P" < 0.05), as well as increased DNA and protein contents and increased total protein synthesis rate in SBS+GLP-2 vs. SBS pigs (+100%, "P" < 0.05). Following intestinal resection in preterm pigs, GLP-2 induced structural and functional adaptation, resulting in a higher relative absorption of fluid and macronutrients. GLP-2 treatment may be a promising therapy to enhance intestinal adaptation and improve digestive function in preterm infants with jejunostomy following intestinal resection.