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 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.
Petersen
Y M
YM
Division of Animal Nutrition, Royal Veterinary and Agricultural University, 3 Grønnegårdsvej, DK-1870 Frederiksberg, Copenhagen, Denmark. yms@kvl.dk
Burrin
D G
DG
Sangild
P T
PT
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology*; D005314:Embryonic and Fetal Development / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005333:Fetus / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D005934:Glucagon / Q000493:pharmacokinetics; D053767:Glucagon-Like Peptide 2; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D010455:Peptides / Q000097:blood / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D018027:Receptors, Glucagon / Q000235:genetics; D013552:Swine; D014158:Transcription, Genetic
C000593833:GLP1R protein, human; C000593835:Glp1r protein, rat; D053767:Glucagon-Like Peptide 2; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D004763:Glucagon-Like Peptides; D005934:Glucagon