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Title: Glucagon-like peptide-2 (GLP-2) increases small intestinal blood flow and mucosal growth in ruminating calves

item TAYLOR-EDWARDS, C - University Of Kentucky
item Burrin, Douglas - Doug
item HOLST, J - University Of Copenhagen
item MCLEOD, K - University Of Kentucky
item HARMON, D - University Of Kentucky

Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/3/2010
Publication Date: 2/1/2011
Citation: Taylor-Edwards, C.C., Burrin, D.G., Holst, J.J., Mcleod, K.R., Harmon, D.L. 2011. Glucagon-like peptide-2 (GLP-2) increases small intestinal blood flow and mucosal growth in ruminating calves. Journal of Dairy Science. 94(2):888-898.

Interpretive Summary: The mechanisms that explain how food stimulates intestinal growth are not completely understood, especially in agriculturally important, domestic animals. Glucagon-like peptide 2 is a hormone produced by the intestine after ingesting food. Our previous studies in neonatal piglet showed that feeding stimulates GLP-2 secretion into the bloodstream. We also showed that infusion of GLP-2 into the bloodstream of piglets, increases intestinal cell growth by increasing the production of new cells and the survival of existing cells. We also showed that infusion of GLP-2 increases intestinal blood flow in neonatal piglets. The aim of the current collaborative study was to test whether the stimulatory actions of GLP-2 occur in another domestic animal species, the dairy calf. The ability to stimulate intestine growth in dairy calves could be an important therapeutic strategy to improve the health and productivity of dairy cattle and potentially milk production. We infused GLP-2 into young, dairy calves for ten days, and measured the effect on intestinal blood flow and cell growth. We found that blood flow to the intestine was markedly increased by GLP-2 infusion at the beginning and end of the ten day period, although the response after ten days was relatively less that the initial day. We also found that GLP-2 infusion, increased the production of new cells that the growth of the intestine. These results are the first to show that GLP-2 induces intestinal growth actions in an agriculturally important animal and may have potential to improve the gut health of dairy calves.

Technical Abstract: Glucagon-like peptide-2 (GLP-2), increases small intestinal mass and blood flow in non-ruminants, but its effect in ruminants is unknown. Eight Holstein calves with an ultrasonic flow probe around the superior mesenteric artery (SMA), and catheters in the carotid artery and mesenteric vein, were paired by age and randomly assigned to treatment of control (0.5% BSA in saline; n = 4), or GLP-2 (50 micrograms/kg BW bovine GLP-2 in BSA; n = 4) given subcutaneously every 12 h for 10 d. Blood flow was measured on d 0 (acute) and d 10 (chronic) and included 3 periods: baseline (saline infusion), treatment (infusion of BSA or 1,000 pmol/kg/h GLP-2), and recovery (saline infusion). On d 11, calves were euthanized 2 h after injection of 5-bromo-2 prime-deoxyuridine (BrdU). Gastrointestinal tissues were weighed and epithelial samples were obtained to determine villus height, crypt depth, and BrdU staining. Infusion of GLP-2 increased superior mesenteric artery blood flow to 175% of baseline on d 0, but to only 137% of baseline after chronic treatment. Compared with control, GLP-2 increased small intestinal mass by 24% by increasing epithelial mass in jejunum and ileum. Additionally, GLP-2 increased villus height, crypt depth, and BrdU-labeling in small intestinal segments. These results demonstrate that GLP-2 induces similar increases in small intestinal blood flow and growth in ruminants as observed in non-ruminants. Furthermore, GLP-2 increases small intestinal blood flow in ruminants but this response is attenuated after 10 d of GLP-2 administration. In cattle, GLP-2 may be an important hormone in the regulation of intestinal blood flow and epithelial growth.