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

  • C. C. Taylor-Edwards (a1), D. G. Burrin (a2), N. B. Kristensen (a3), J. J. Holst (a4), K. R. McLeod (a1) and D. L. Harmon (a1)...


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 μg/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 μg/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, β-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 [U13-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.


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Battezzati, A, Brillon, DJ, Matthews, DE 1995. Oxidation of glutamic acid by the splanchnic bed in humans. American Journal of Physiology 269, E269E276.
Bergman, EN, Heitmann, RN 1978. Metabolism of amino acids by the gut, liver, kidneys, and peripheral tissues. Federation Proceedings 37, 12281232.
Bertolo, RF, Burrin, DG 2008. Comparative aspects of tissue glutamine and proline metabolism. Journal of Nutrition 138, Supplement: 7th Amino Acid Assessment Workshop, 2032S2039S.
Bremholm, L, Hornum, M, Andersen, UB, Holst, JJ 2010. The effect of glucagon-like peptide-2 on arterial blood flow and cardiac parameters. Regulatory Peptides 159, 6771.
Bremholm, L, Hornum, M, Henriksen, BM, Larsen, S, Holst, JJ 2009. Glucagon-like peptide-2 increases mesenteric blood flow in humans. Scandanavian Journal of Gastroenterology 44, 314319.
Brubaker, PL, Izzo, A, Hill, M, Drucker, DJ 1997. Intestinal function in mice with small bowel growth induced by glucagon-like peptide-2. American Journal of Physiology 272, E1050E1058.
Burrin, DG, Stoll, B, Guan, X 2003. Glucagon-like peptide 2 function in domestic animals. Domestic Animal Endocrinology 24, 103122.
Curis, E, Crenn, P, Cynober, L 2007. Citrulline and the gut. Current Opinion in Clinical Nutrition and Metabolic Care 10, 620626.
Curis, E, Nicolis, I, Moinard, C, Osowska, S, Zerrouk, N, Benazeth, S, Cynober, L 2005. Almost all about citrulline in mammals. Amino Acids 29, 177205.
Deniz, M, Bozkurt, A, Kurtel, H 2007. Mediators of glucagon-like peptide 2-induced blood flow: responses in different vascular sites. Regulatory Peptides 142, 715.
Drucker, DJ, DeForest, L, Brubaker, PL 1997. Intestinal response to growth factors administered alone or in combination with human [Gly2]glucagon-like peptide 2. American Journal of Physiology 273, G1252G1262.
Guan, X, Stoll, B, Lu, X, Tappenden, KA, Holst, JJ, Hartmann, B, Burrin, DG 2003. GLP-2-mediated up-regulation of intestinal blood flow and glucose uptake is nitric oxide-dependent in TPN-fed piglets 1. Gastroenterology 125, 136147.
Guan, X, Karpen, HE, Stephens, J, Bukowski, JT, Niu, S, Zhang, G, Stoll, B, Finegold, MJ, Holst, JJ, Hadsell, DL, Nichols, BL, Burrin, DG 2006. GLP-2 receptor localizes to enteric neurons and endocrine cells expressing vasoactive peptides and mediates increased blood flow. Gastroenterology 130, 150164.
Harvey, RB, Brothers, AJ 1962. Renal extraction of para-aminohippurate and creatinine measured by continuous in vivo sampling of arterial and renal-vein blood. Annals New York Academy of Science 102, 4654.
Kristensen, NB, Danfaer, A, Rojen, BA, Raun, BM, Weisbjerg, MR, Hvelplund, T 2002. Metabolism of propionate and 1,2-propanediol absorbed from the washed reticulorumen of lactating cows. Journal of Animal Science 80, 21682175.
Lomax, MA, Baird, GD 1983. Blood flow and nutrient exchange across the liver and gut of the dairy cow. Effects of lactation and fasting. British Journal of Nutrition 49, 481496.
Lopez, LC, Frazier, ML, Su, CJ, Kumar, A, Saunders, GF 1983. Mammalian pancreatic preproglucagon contains three glucagon-related peptides. Proceedings National Academy of Science (U.S.A.) 80, 54855489.
Marsh, WH, Fingerhut, B, Miller, H 1965. Automated and manual direct methods for the determination of blood urea. Clinical Chemistry 11, 624627.
Massimino, SP, McBurney, MI, Field, CJ, Thomson, AB, Keelan, M, Hayek, MG, Sunvold, GD 1998. Fermentable dietary fiber increases GLP-1 secretion and improves glucose homeostasis despite increased intestinal glucose transport capacity in healthy dogs. Journal of Nutrition 128, 17861793.
McBride, BW, Kelly, JM 1990. Energy cost of absorption and metabolism in the ruminant gastrointestinal tract and liver: a review. Journal of Animal Science 68, 29973010.
McCauley, RD, Heel, KA, Christiansen, KJ, Hall, JC 1996. The effect of minimum luminal nutrition on bacterial translocation and atrophy of the jejunum during parenteral nutrition. Journal of Gastroenterology and Hepatology 11, 6570.
Meier, JJ, Nauck, MA, Pott, A, Heinze, K, Goetze, O, Bulut, K, Schmidt, WE, Gallwitz, B, Holst, JJ 2006. Glucagon-like peptide 2 stimulates glucagon secretion, enhances lipid absorption, and inhibits gastric acid secretion in humans. Gastroenterology 130, 4454.
Oba, M, Baldwin, RL, Bequette, BJ 2004. Oxidation of glucose, glutamate, and glutamine by isolated ovine enterocytes in vitro is decreased by the presence of other metabolic fuels. Journal of Animal Science 82, 479486.
Orskov, C, Hartmann, B, Poulsen, SS, Thulesen, J, Hare, KJ, Holst, JJ 2005. GLP-2 stimulates colonic growth via KGF, released by subepithelial myofibroblasts with GLP-2 receptors. Regulatory Peptides 124, 105112.
Sorensen, LB, Flint, A, Raben, A, Hartmann, B, Holst, JJ, Astrup, A 2003. No effect of physiological concentrations of glucagon-like peptide-2 on appetite and energy intake in normal weight subjects. International Journal of Obesity and Related Metabolic Disorders 27, 450456.
Stephens, J, Stoll, B, Cottrell, J, Chang, X, Helmrath, M, Burrin, DG 2006. Glucagon-like peptide-2 acutely increases proximal small intestinal blood flow in TPN-fed neonatal piglets. Amererican Journal of Physiology 290, R283R289.
Stoll, B, Chang, X, Fan, MZ, Reeds, PJ, Burrin, DG 2000. Enteral nutrient intake level determines intestinal protein synthesis and accretion rates in neonatal pigs. American Journal of Physiology 279, G288G294.
Taylor-Edwards, CC, Burrin, DG, Holst, JJ, McLeod, KR, Harmon, DL 2011. Glucagon-like peptide-2 (GLP-2) increases small intestinal blood flow and mucosal growth in ruminating calves. Journal of Dairy Science 94, 888898.
Tsai, CH, Hill, M, Drucker, DJ 1997a. Biological determinants of intestinotrophic properties of GLP-2 in vivo. American Journal of Physiology 272, G662G668.
Tsai, CH, Hill, M, Asa, SL, Brubaker, PL, Drucker, DJ 1997b. Intestinal growth-promoting properties of glucagon-like peptide-2 in mice. American Journal of Physiology 273, E77E84.
Urschel, KL, Evans, AR, Wilkinson, CW, Pencharz, PB, Ball, RO 2007. Parenterally fed neonatal piglets have a low rate of endogenous arginine synthesis from circulating proline. Journal of Nutrition 137, 601606.
Windmueller, HG, Spaeth, AE 1974. Uptake and metabolism of plasma glutamine by the small intestine. Journal of Biological Chemistry 249, 50705079.


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

  • C. C. Taylor-Edwards (a1), D. G. Burrin (a2), N. B. Kristensen (a3), J. J. Holst (a4), K. R. McLeod (a1) and D. L. Harmon (a1)...


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