Hostname: page-component-8448b6f56d-sxzjt Total loading time: 0 Render date: 2024-04-18T13:50:09.866Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  09 May 2012

C. C. Taylor-Edwards ,
D. G. Burrin ,
N. B. Kristensen ,
J. J. Holst ,
K. R. McLeod  and
D. L. Harmon
C. C. Taylor-Edwards
Affiliation:
Department of Animal and Food Sciences, University of Kentucky, Lexington, KY 40546, USA
D. G. Burrin
Affiliation:
USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USA
N. B. Kristensen
Affiliation:
Department of Animal Health and Bioscience, Aarhus University, Tjele, DK-8830 Denmark
J. J. Holst
Affiliation:
Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, DK-2200 Denmark
K. R. McLeod
Affiliation:
Department of Animal and Food Sciences, University of Kentucky, Lexington, KY 40546, USA
D. L. Harmon*
Affiliation:
Department of Animal and Food Sciences, University of Kentucky, Lexington, KY 40546, USA
*
†E-mail: dharmon@uky.edu
Get access

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 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.

Keywords

blood flowglucoseamino acidfluxruminant
Type
Physiology and functional biology of systems
Information
animal , Volume 6 , Issue 12 , December 2012 , pp. 1985 - 1997
Copyright
Copyright © The Animal Consortium 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Battezzati, A, Brillon, DJ, Matthews, DE 1995. Oxidation of glutamic acid by the splanchnic bed in humans. American Journal of Physiology 269, E269–E276.Google Scholar
Bergman, EN, Heitmann, RN 1978. Metabolism of amino acids by the gut, liver, kidneys, and peripheral tissues. Federation Proceedings 37, 1228–1232.Google ScholarPubMed
Bertolo, RF, Burrin, DG 2008. Comparative aspects of tissue glutamine and proline metabolism. Journal of Nutrition 138, Supplement: 7th Amino Acid Assessment Workshop, 2032S–2039S.Google Scholar
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, 67–71.CrossRefGoogle ScholarPubMed
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, 314–319.CrossRefGoogle ScholarPubMed
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, E1050–E1058.Google Scholar
Burrin, DG, Stoll, B, Guan, X 2003. Glucagon-like peptide 2 function in domestic animals. Domestic Animal Endocrinology 24, 103–122.Google Scholar
Curis, E, Crenn, P, Cynober, L 2007. Citrulline and the gut. Current Opinion in Clinical Nutrition and Metabolic Care 10, 620–626.Google Scholar
Curis, E, Nicolis, I, Moinard, C, Osowska, S, Zerrouk, N, Benazeth, S, Cynober, L 2005. Almost all about citrulline in mammals. Amino Acids 29, 177–205.Google Scholar
Deniz, M, Bozkurt, A, Kurtel, H 2007. Mediators of glucagon-like peptide 2-induced blood flow: responses in different vascular sites. Regulatory Peptides 142, 7–15.Google Scholar
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, G1252–G1262.Google Scholar
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, 136–147.Google Scholar
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, 150–164.Google Scholar
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, 46–54.Google Scholar
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, 2168–2175.Google Scholar
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, 481–496.Google Scholar
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, 5485–5489.Google Scholar
Marsh, WH, Fingerhut, B, Miller, H 1965. Automated and manual direct methods for the determination of blood urea. Clinical Chemistry 11, 624–627.Google Scholar
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, 1786–1793.Google Scholar
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, 2997–3010.Google Scholar
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, 65–70.Google Scholar
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, 44–54.Google Scholar
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, 479–486.Google Scholar
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, 105–112.Google Scholar
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, 450–456.Google Scholar
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, R283–R289.Google Scholar
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, G288–G294.Google Scholar
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, 888–898.Google Scholar
Tsai, CH, Hill, M, Drucker, DJ 1997a. Biological determinants of intestinotrophic properties of GLP-2 in vivo. American Journal of Physiology 272, G662–G668.Google Scholar
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, E77–E84.Google Scholar
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, 601–606.Google Scholar
Windmueller, HG, Spaeth, AE 1974. Uptake and metabolism of plasma glutamine by the small intestine. Journal of Biological Chemistry 249, 5070–5079.Google Scholar