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Title: Glucagon-like peptide-2 (GLP-2) increases net amino acid utilization by the portal-drained viscera of ruminatinhg calves

item TAYLOR-EDWARDS, C. - University Of Kentucky
item Burrin, Douglas - Doug
item KRISTENSEN, N. - Aarhus University
item HOLST, JENS - University Of Copenhagen
item MCLEOD, KYLE - University Of Kentucky
item HARMON, DAVID - University Of Kentucky

Submitted to: Animal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/27/2012
Publication Date: 5/9/2012
Citation: Taylor-Edwards, C.C., Burrin, D.G., Kristensen, N.B., Holst, J.J., McLeod, K.R., Harmon, D.L. 2012. Glucagon-like peptide-2 (GLP-2) increases net amino acid utilization by the portal-drained viscera of ruminatinhg calves. Animal. 6(12):1985-1997.

Interpretive Summary: Glucagon-like peptide-2 (GLP-2) is a gut growth factor whose secretion is stimulated by the ingestion of food. We previously showed that infusion of GLP-2 increases small intestinal mass and blood flow in ruminant calves. The growth and development of the gut and liver tissues of the developing ruminant calf is important for normal growth of dairy and beef production animals. Based on our findings that GLP-2 increased blood flow and growth of the intestine, we tested further whether these effects translated into improved nutrient absorption to the calves. We studied young calves treated with GLP-2 for 10 days and measured nutrient use by the gut before and after treatment. We found that many amino acids were preferentially extracted from the blood in order maintain growth of the intestine in GLP-2 treated calves compared to control animals. Many of the amino acids extracted from the blood are used specifically by the gut for energy. Despite these results, we did not find a similar preferential use of glucose by the gut. Our results suggest that the growth effects of GLP-2 translate into increased nutrient requirements for the gut, mainly in the form of amino acids, rather than glucose.

Technical Abstract: Glucagon-like peptide-2 (GLP-2) increases small intestinal mass and blood flow in ruminant calves, but its impact on nutrient metabolism across the portal-drained viscera (PDV) and liver is unknown. Eight Holstein calves with catheters in the carotid artery, mesenteric vein, portal vein and hepatic vein were paired by age and randomly assigned to control (0.5% bovine serum albumin in saline; n = 4) or GLP-2 (100 micro g per kg BW per day bovine GLP-2 in bovine serum albumin; n = 4). Treatments were administered subcutaneously every 12 h for 10 days. Blood flow was measured on days 0 and 10 and included 3 periods: baseline (saline infusion), treatment (infusion of bovine serum albumin or 3.76 micro g per kg BW per h GLP-2), and recovery (saline infusion). Arterial concentrations and net PDV, hepatic, and total splanchnic fluxes of glucose, lactate, glutamate, glutamine, beta-hydroxybutyrate, and urea-N were measured on days 0 and 10. Arterial concentrations and net fluxes of all amino acids and glucose metabolism using continuous intravenous infusion of [U(13)-C]glucose were measured on day 10 only. A 1-h infusion of GLP-2 increased blood flow in the portal and hepatic veins when administered to calves not previously exposed to exogenous GLP-2, but after a 10-day administration of GLP-2 the blood flow response to the 1-h GLP-2 infusion was substantially attenuated. The 1-h GLP-2 infusion also did not appreciably alter nutrient fluxes on either day 0 or 10. In contrast, long-term GLP-2 administration reduced arterial concentrations and net PDV flux of many essential and non-essential amino acids. Despite the significant alterations in amino acid metabolism, glucose irreversible loss and utilization by PDV and non-PDV tissues were not affected by GLP-2. Fluxes of amino acids across the PDV were generally reduced by GLP-2, potentially by increased small intestinal epithelial growth, and thus energy and amino acid requirements of this tissue. Increased PDV extraction of glutamine and alterations in PDV metabolism of arginine, ornithine, and citrulline support the concept that GLP-2 influences intestine-specific amino acid metabolism. Alterations in amino acid metabolism but unchanged glucose metabolism suggests that the growth effects induced by GLP-2 in ruminants increase reliance on amino acids preferentially over glucose. Thus, GLP-2 increases PDV utilization of amino acids, but not glucose, concurrent with stimulated growth of the small intestinal epithelium in post-absorptive ruminant calves.