|Burrin, Douglas - Doug|
Submitted to: American Journal of Physiology - Regulatory Integrative & Comparative Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/14/2001
Publication Date: 12/1/2001
Citation: Petersen,Y.M., Burrin,D.G., Sangild,P.T. 2001. GLP-2 has differential effects on small intestine growth and function in fetal and neonatal pigs. American Journal of Physiology - Regulatory Integrative and Comparative Physiology 281:(6):R1986-R1993. Interpretive Summary: The intestine of developing animals undergoes significant growth in the period just before and after birth. Glucagon-like peptide 2 is a hormone present in the blood and our previous studies have shown that it is a potent stimulus of intestinal growth in newborn piglets. The aim of this study was to see whether infusing GLP-2 into the blood of fetal piglets would also stimulate intestinal growth. Fetal piglets were surgically implanted with small tubes in their blood vessels and placed back in the mother's uterus. Then the piglets were infused with a solution with or without GLP-2 for six days. We also studied a group of newborn piglets that were fed exclusively via small tubes in the blood vessels, called total parenteral nutrition or TPN, and infused with GLP-2 for six days. After six days the piglets were removed from the uterus and euthanized to measure the growth of the intestine. We found that GLP-2 infusion increased the intestinal growth in the newborn, TPN-fed piglets, but not the fetal piglets. We also failed to see any effect of GLP-2 on the development of intestinal enzymes that digest food. These results suggest that, in contrast to the newborn pig, the fetal piglet intestine does not respond to stimulatory actions of GLP-2 while it is still in the mother's uterus.
Technical Abstract: GLP-2 has differential effect 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 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 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 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.