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

Glucagon-like peptide-2 (GLP-2) is a potent intestinotropic factor in neona tal and adult animals. However, the GLP-2 responsiveness of the fetal intes tine has not been established. To determine how stage of development affect s the responsiveness to GLP-2, we examined GLP-2 receptor (GLP-2R) expressi on, gut morphology, and brush-border enzyme mRNA and activities in late-ges tation fetal (n = 7) and parenterally fed neonatal (n = 7) piglets given GL P-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 GLP2-(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 GL P-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. Aminop eptidase 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 ne onates. This may be related to the normal developmental changes in intestin e growth and function and to a maturation of the GLP-2R signaling pathways around the time of birth.