GLP-2 has differential effects on small intestine growth and function in fetal and neonatal pigs

Am J Physiol Regul Integr Comp Physiol. 2001 Dec;281(6):R1986-93. doi: 10.1152/ajpregu.2001.281.6.R1986.


Glucagon-like peptide-2 (GLP-2) is a potent intestinotropic factor in neonatal and adult animals. However, the GLP-2 responsiveness of the fetal intestine has not been established. To determine how stage of development affects the responsiveness to GLP-2, we examined GLP-2 receptor (GLP-2R) expression, gut morphology, and brush-border enzyme mRNA and activities in late-gestation fetal (n = 7) and parenterally fed neonatal (n = 7) piglets given GLP-2 (12.5 nmol/kg) twice daily for 6 days. The GLP-2R was expressed in the fetal and neonatal gastrointestinal tract. The biologically active GLP-2-(1-33) was undetectable (<5 pmol/l) in plasma of 98-day-gestation fetuses but increased significantly toward full term (115 days, 11 +/- 1 pmol/l) and in neonates fed by total parenteral nutrition (23 +/- 5 pmol/l). Exogenous GLP-2 had no effect on gut growth in fetuses but increased intestinal weight and villus height in neonates (P < 0.05). Crypt cell proliferation and the enzymes sucrase-isomaltase, lactase-phloridzin hydrolase, aminopeptidase A, and dipeptidyl peptidase IV were unchanged by GLP-2 in both groups. Aminopeptidase N mRNA and activity were increased in fetuses, while maltase mRNA and activity were increased in neonates. In conclusion, exogenous GLP-2 had different effects on small intestine growth and function in fetuses and neonates. This may be related to the normal developmental changes in intestine growth and function and to a maturation of the GLP-2R signaling pathways around the time of birth.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn / growth & development
  • Animals, Newborn / physiology*
  • Embryonic and Fetal Development / drug effects
  • Embryonic and Fetal Development / physiology*
  • Female
  • Fetus / physiology*
  • Gene Expression Regulation, Developmental
  • Glucagon / pharmacokinetics
  • Glucagon-Like Peptide 2
  • Glucagon-Like Peptide-1 Receptor
  • Glucagon-Like Peptides
  • Humans
  • Intestine, Small / drug effects
  • Intestine, Small / growth & development
  • Intestine, Small / physiology*
  • Peptides / blood
  • Peptides / pharmacology*
  • Pregnancy
  • Rats
  • Receptors, Glucagon / genetics
  • Swine
  • Transcription, Genetic


  • GLP1R protein, human
  • Glp1r protein, rat
  • Glucagon-Like Peptide 2
  • Glucagon-Like Peptide-1 Receptor
  • Peptides
  • Receptors, Glucagon
  • Glucagon-Like Peptides
  • Glucagon