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

Am J Physiol Gastrointest Liver Physiol. 2013 Aug 15;305(4):G277-85. doi: 10.1152/ajpgi.00064.2013. Epub 2013 Jun 13.

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 h 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 μg/kg body wt per h, 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 h, 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.

Keywords: glucagon-like peptide-2; intestine; neonatal short bowel syndrome; premature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Animal Nutritional Physiological Phenomena
  • Animals
  • Animals, Newborn
  • Cell Proliferation / drug effects
  • DNA Replication / drug effects
  • Disease Models, Animal
  • Enteral Nutrition
  • Gestational Age
  • Glucagon-Like Peptide 2 / blood
  • Glucagon-Like Peptide 2 / pharmacology*
  • Humans
  • Intestinal Absorption / drug effects
  • Intestine, Small / drug effects*
  • Intestine, Small / growth & development
  • Intestine, Small / metabolism
  • Intestine, Small / pathology
  • Intestine, Small / surgery*
  • Jejunostomy
  • Nutritional Status
  • Parenteral Nutrition, Total
  • Premature Birth*
  • Protein Biosynthesis / drug effects
  • Recombinant Proteins / pharmacology
  • Short Bowel Syndrome / blood
  • Short Bowel Syndrome / drug therapy*
  • Short Bowel Syndrome / etiology
  • Short Bowel Syndrome / pathology
  • Short Bowel Syndrome / physiopathology
  • Sucrase / metabolism
  • Swine
  • Time Factors
  • Weight Gain / drug effects
  • alpha-Glucosidases / metabolism

Substances

  • Glucagon-Like Peptide 2
  • Recombinant Proteins
  • alpha-Glucosidases
  • Sucrase