GLP-2 stimulates intestinal growth in premature TPN-fed pigs by suppressing proteolysis and apoptosis

Am J Physiol Gastrointest Liver Physiol. 2000 Dec;279(6):G1249-56. doi: 10.1152/ajpgi.2000.279.6.G1249.


We wished to determine whether exogenous glucagon-like peptide (GLP)-2 infusion stimulates intestinal growth in parenterally fed immature pigs. Piglets (106-108 days gestation) were given parenteral nutrient infusion (TPN), TPN + human GLP-2 (25 nmol. kg(-1). day(-1)), or sow's milk enterally (ENT) for 6 days. Intestinal protein synthesis was then measured in vivo after a bolus dose of [1-(13)C]phenylalanine, and degradation was calculated from the difference between protein accretion and synthesis. Crypt cell proliferation and apoptosis were measured in situ by 5-bromodeoxyuridine (BrdU) and terminal dUTP nick-end labeling (TUNEL), respectively. Intestinal protein and DNA accretion rates and villus heights were similar in GLP-2 and ENT pigs, and both were higher (P < 0.05) than in TPN pigs. GLP-2 decreased fractional protein degradation rate, whereas ENT increased fractional protein synthesis rate compared with TPN pigs. Percentage of TUNEL-positive cells in GLP-2 and ENT groups was 48 and 64% lower, respectively, than in TPN group (P < 0.05). However, ENT, but not GLP-2, increased percentage of BrdU-positive crypt cells above that in TPN piglets. We conclude that GLP-2 increases intestinal growth in premature, TPN-fed pigs by decreasing proteolysis and apoptosis, whereas enteral nutrition acts via increased protein synthesis and cell proliferation and decreased apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis*
  • Dietary Proteins / metabolism*
  • Enteral Nutrition
  • Female
  • Gastric Mucosa / metabolism
  • Glucagon-Like Peptide 2
  • Glucagon-Like Peptides
  • Humans
  • In Situ Nick-End Labeling
  • Intestinal Mucosa / metabolism
  • Intestine, Large / drug effects
  • Intestine, Large / growth & development
  • Intestine, Large / metabolism
  • Intestines / drug effects
  • Intestines / growth & development*
  • Male
  • Pancreas / drug effects
  • Pancreas / growth & development
  • Pancreas / metabolism
  • Parenteral Nutrition, Total*
  • Peptides / blood
  • Peptides / pharmacology*
  • Stomach / drug effects
  • Stomach / growth & development
  • Swine


  • Dietary Proteins
  • Glucagon-Like Peptide 2
  • Peptides
  • Glucagon-Like Peptides