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Glutamine, arginine, and leucine signaling in the intestine

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Abstract

Glutamine and leucine are abundant constituents of plant and animal proteins, whereas the content of arginine in foods and physiological fluids varies greatly. Besides their role in protein synthesis, these three amino acids individually activate signaling pathway to promote protein synthesis and possibly inhibit autophagy-mediated protein degradation in intestinal epithelial cells. In addition, glutamine and arginine stimulate the mitogen-activated protein kinase and mammalian target of rapamycin (mTOR)/p70 (s6) kinase pathways, respectively, to enhance mucosal cell migration and restitution. Moreover, through the nitric oxide-dependent cGMP signaling cascade, arginine regulates multiple physiological events in the intestine that are beneficial for cell homeostasis and survival. Available evidence from both in vitro and in vivo animal studies shows that glutamine and arginine promote cell proliferation and exert differential cytoprotective effects in response to nutrient deprivation, oxidative injury, stress, and immunological challenge. Additionally, when nitric oxide is available, leucine increases the migration of intestinal cells. Therefore, through cellular signaling mechanisms, arginine, glutamine, and leucine play crucial roles in intestinal growth, integrity, and function.

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Abbreviations

ARG:

l-Arginine

ERK:

Extracellular signal-related kinase

GLN:

l-Glutamine

HO:

Heme oxygenase

hsp:

Heat shock proteins

LEU:

l-Leucine

MAPK:

Mitogen-activated protein kinase

MEK:

MAPK kinase

mTOR:

Mammalian target of rapamycin

NO:

Nitric oxide

References

  • Alican I, Kubes P (1996) A critical role for nitric oxide in intestinal barrier function and dysfunction. Am J Physiol 270:G225–G237

    PubMed  CAS  Google Scholar 

  • Argenzio RA, Rhoads JM, Armstrong M, Gomez G (1994) Glutamine stimulates prostaglandin-sensitive Na(+)-H+ exchange in experimental porcine cryptosporidiosis. Gastroenterology 106:1418–1428

    PubMed  CAS  Google Scholar 

  • Avissar NE, Ziegler TR, Toia L et al (2004) ATB0/ASCT2 expression in residual rabbit bowel is decreased after massive enterectomy and is restored by growth hormone treatment. J Nutr 134:2173–2177

    PubMed  CAS  Google Scholar 

  • Ban H, Shigemitsu K, Yamatsuji T et al (2004) Arginine and Leucine regulate p70 s6kinase and 4E-BP1 in intestinal epithelial cells. Int J Mol Med 13:537–543

    PubMed  CAS  Google Scholar 

  • Barbul A (1986) Arginine: biochemistry, physiology, and therapeutic implications. J Parenter Enteral Nutr 10:227–238

    Article  CAS  Google Scholar 

  • Beale RJ, Sherry T, Lei K et al (2008) Early enteral supplementation with key pharmaconutrients improves sequential organ failure assessment score in critically ill patients with sepsis: outcome of a randomized, controlled, double-blind trial. Crit Care Med 36:131–144

    Article  PubMed  CAS  Google Scholar 

  • Becker RM, Wu G, Galanko JA et al (2000) Reduced serum amino acid concentrations in infants with necrotizing enterocolitis. J Pediatr 137:785–793

    Article  PubMed  CAS  Google Scholar 

  • Bilban M, Haschemi A, Wegiel B et al (2008) Heme oxygenase and carbon monoxide initiate homeostatic signaling. J Mol Med 86:267–279

    Article  PubMed  CAS  Google Scholar 

  • Blachier F, Mariotti F, Huneau JF, Tomé D (2007) Effects of amino acid-derived luminal metabolites on the colonic epithelium and physiopathological consequences. Amino Acids 33:547–562

    Article  PubMed  CAS  Google Scholar 

  • Blikslager AT, Rhoads JM, Bristol DG et al (1999) Glutamine and transforming growth factor-alpha stimulate extracellular regulated kinases and enhance recovery of villous surface area in porcine ischemic-injured intestine. Surgery 125:186–194

    PubMed  CAS  Google Scholar 

  • Blommaart EF, Luiken JJ, Blommaart PJ et al (1995) Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes. J Biol Chem 270:2320–2326

    Article  PubMed  CAS  Google Scholar 

  • Boelens PG, Nijveldt RJ, Houdijk AP et al (2001) Glutamine alimentation in catabolic state. J Nutr 131:2569S–2577S

    PubMed  CAS  Google Scholar 

  • Buchman AL (2001) Glutamine: commercially essential or conditionally essential? A critical appraisal of the human data. Am J Clin Nutr 74:25–32

    PubMed  CAS  Google Scholar 

  • Chen LX, Yin YL, Jobgen WS et al (2007) In vitro oxidation of essential amino acids by jejunal mucosal cells of growing pigs. Livest Sci 109:19–23

    Article  Google Scholar 

  • Chen G, Shi J, Qi M et al (2008) Glutamine decreases intestinal nuclear factor kappa B activity and pro-inflammatory cytokine expression after traumatic brain injury in rats. Inflamm Res 57:57–64

    Article  PubMed  CAS  Google Scholar 

  • Coeffier M, Miralles-Barrachina O, Le PF et al (2001) Influence of glutamine on cytokine production by human gut in vitro. Cytokine 13:148–154

    Article  PubMed  CAS  Google Scholar 

  • Coeffier M, Marion R, Ducrotte P, Dechelotte P (2003) Modulating effect of glutamine on IL-1beta-induced cytokine production by human gut. Clin Nutr 22:407–413

    Article  PubMed  CAS  Google Scholar 

  • Corl BA, Odle J, Niu X et al (2008) Arginine activates intestinal p70(s6k) and protein synthesis in piglet rotavirus enteritis. J Nutr 138:24–29

    PubMed  CAS  Google Scholar 

  • Curis E, Crenn P, Cynober L (2007) Citrulline and the gut. Curr Opin Clin Nutr Metab Care 10:620–626

    Article  PubMed  CAS  Google Scholar 

  • Dalmasso G, Charrier-Hisamuddin L, Thu Nguyen HT et al (2008) PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology 134:166–178

    Article  PubMed  CAS  Google Scholar 

  • Deniel N, Marion-Letellier R, Charlionet R et al (2007) Glutamine regulates the human epithelial intestinal HCT-8 cell proteome under apoptotic conditions. Mol Cell Proteomics 6:1671–1679

    Article  PubMed  CAS  Google Scholar 

  • Derikx JP, Poeze M, van Bijnen AA et al (2007) Evidence for intestinal and liver epithelial cell injury in the early phase of sepsis. Shock 28:544–548

    PubMed  CAS  Google Scholar 

  • Di LM, Krantis A (2002) Nitric oxide synthase isoenzyme activities in a premature piglet model of necrotizing enterocolitis: effects of nitrergic manipulation. Pediatr Surg Int 18:624–629

    Article  Google Scholar 

  • Evans ME, Jones DP, Ziegler TR (2003) Glutamine prevents cytokine-induced apoptosis in human colonic epithelial cells. J Nutr 133:3065–3071

    PubMed  CAS  Google Scholar 

  • Fischer CP, Bode BP, Abcouwer SF et al (1995) Hepatic uptake of glutamine and other amino acids during infection and inflammation. Shock 3:315–322

    Article  PubMed  CAS  Google Scholar 

  • Flynn NE, Bird JG, Guthrie AS (2008) Glucocorticoid regulation of amino acid and polyamine metabolism in the small intestine. Amino Acids. doi:10.1007/s00726-008-0206-7

  • Fu WJ, Haynes TE, Kohli R (2005) Dietary l-arginine supplementation reduces fat mass in Zucker diabetic fatty rats. J Nutr 135:714–721

    PubMed  CAS  Google Scholar 

  • Fuchs BC, Perez JC, Suetterlin JE et al (2004) Inducible antisense RNA targeting amino acid transporter ATB0/ASCT2 elicits apoptosis in human hepatoma cells. Am J Physiol Gastrointest Liver Physiol 286:G467–G478

    Article  PubMed  CAS  Google Scholar 

  • Giris M, Erbil Y, Oztezcan S et al (2006) The effect of heme oxygenase-1 induction by glutamine on radiation-induced intestinal damage: the effect of heme oxygenase-1 on radiation enteritis. Am J Surg 191:503–509

    Article  PubMed  CAS  Google Scholar 

  • Gookin JL, Foster DM, Coccaro MR, Stauffer SH (2008) Oral delivery of l-arginine stimulates prostaglandin-dependent secretory diarrhea in Cryptosporidium parvum-infected neonatal piglets. J Pediatr Gastroenterol Nutr 46:139–146

    Article  PubMed  CAS  Google Scholar 

  • Hayashi M, Sakai T, Hasegawa Y et al (1999) Physiological mechanism for enhancement of paracellular drug transport. J Control Release 62:141–148

    Article  PubMed  CAS  Google Scholar 

  • He QH, Kong XF, Wu G et al. (2008) Metabolomic analysis of the response of growing pigs to dietary l-arginine supplementation. Amino Acids. doi:10.1007/s00726-008-0192-9

  • Houdijk AP, Rijnsburger ER, Jansen J et al (1998) Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma. Lancet 352:772–776

    Article  PubMed  CAS  Google Scholar 

  • Ito Y, Doelle SM, Clark JA et al (2007) Intestinal microcirculatory dysfunction during the development of experimental necrotizing enterocolitis. Pediatr Res 61:180–184

    Article  PubMed  Google Scholar 

  • Jiang ZM, Wang LJ, Qi Y et al (1993) Comparison of parenteral nutrition supplemented with l-glutamine or glutamine dipeptides. J Parenter Enteral Nutr 17:134–141

    Article  CAS  Google Scholar 

  • Jobgen WS, Fried SK, Fu WJ et al (2006) Regulatory role for the arginine-nitric oxide pathway in metabolism of energy substrates. J Nutr Biochem 17:571–588

    Article  PubMed  CAS  Google Scholar 

  • Jobgen WJ, Meininger CJ, Jobgen SC et al. (2008) Dietary l-arginine supplementation reduces white-fat gain and enhances skeletal muscle and brown fat masses in diet-induced obese rats. J Nutr. doi:10.3945/jn.108.096362

  • Kadowaki M, Kanazawa T (2003) Amino acids as regulators of proteolysis. J Nutr 133:2052S–2056S

    PubMed  CAS  Google Scholar 

  • Kim SW, Wu G (2008) Regulatory role for amino acids in mammary gland growth and milk synthesis. Amino Acids. doi:10.1007/s00726-008-0151-5

  • Kimball SR, Jefferson LS (2006) New functions for amino acids: effects on gene transcription and translation. Am J Clin Nutr 83:500S–507S

    PubMed  CAS  Google Scholar 

  • Ko TC, Beauchamp RD, Townsend CM Jr, Thompson JC (1993) Glutamine is essential for epidermal growth factor-stimulated intestinal cell proliferation. Surgery 114:147–153

    PubMed  CAS  Google Scholar 

  • Ko YG, Kim EY, Kim T et al (2001) Glutamine-dependent antiapoptotic interaction of human glutaminyl-tRNA synthetase with apoptosis signal-regulating kinase 1. J Biol Chem 276:6030–6036

    Article  PubMed  CAS  Google Scholar 

  • Kozar RA, Verner-Cole E, Schultz SG et al (2004) The immune-enhancing enteral agents arginine and glutamine differentially modulate gut barrier function following mesenteric ischemia/reperfusion. J Trauma 57:1150–1156

    Article  PubMed  CAS  Google Scholar 

  • Krane SM (2008) The importance of proline residues in the structure, stability and susceptibility to proteolytic degradation of collagens. Amino Acids 35:703–710

    Article  PubMed  CAS  Google Scholar 

  • Kwon H, Spencer TE, Bazer FW, Wu G (2003) Developmental changes of amino acids in ovine fetal fluids. Biol Reprod 68:1813–1820

    Article  PubMed  CAS  Google Scholar 

  • Larson SD, Li J, Chung DH, Evers BM (2007) Molecular mechanisms contributing to glutamine-mediated intestinal cell survival. Am J Physiol Gastrointest Liver Physiol 293:G1262–G1271

    Article  PubMed  CAS  Google Scholar 

  • Lenaerts K, Renes J, Bouwman FG et al (2007) Arginine deficiency in preconfluent intestinal Caco-2 cells modulates expression of proteins involved in proliferation, apoptosis, and heat shock response. Proteomics 7:565–577

    Article  PubMed  CAS  Google Scholar 

  • Lentze MJ (1989) Intestinal adaptation in short-bowel syndrome. Eur J Pediatr 148:294–299

    Article  PubMed  CAS  Google Scholar 

  • Li N, Lewis P, Samuelson D et al (2004) Glutamine regulates Caco-2 cell tight junction proteins. Am J Physiol Gastrointest Liver Physiol 287:G726–G733

    Article  PubMed  CAS  Google Scholar 

  • Liao XH, Majithia A, Huang X, Kimmel AR (2008) Growth control via TOR kinase signaling, an intracellular sensor of amino acid and energy availability, with crosstalk potential to proline metabolism. Amino Acids 35:761–770

    Article  PubMed  CAS  Google Scholar 

  • Liu L, Chen L, Chung J, Huang S (2008) Rapamycin inhibits F-actin reorganization and phosphorylation of focal adhesion proteins. Oncogene 27:4998–5010

    Article  PubMed  CAS  Google Scholar 

  • Luo CC, Chen HM, Chiu CH et al (2001) Effect of N(G)-nitro-l-arginine methyl ester on intestinal permeability following intestinal ischemia-reperfusion injury in a rat model. Biol Neonate 80:60–63

    Article  PubMed  CAS  Google Scholar 

  • Martín-Rufián M, Segura JA, Lobo C et al (2006) Identification of genes downregulated in tumor cells expressing antisense glutaminase mRNA by differential display. Cancer Biol Ther 5:54–58

    Article  PubMed  Google Scholar 

  • McCormack SA, Johnson LR (1991) Role of polyamines in gastrointestinal mucosal growth. Am J Physiol 260:G795–G806

    PubMed  CAS  Google Scholar 

  • Nakajo T, Yamatsuji T, Ban H et al (2005) Glutamine is a key regulator for amino acid-controlled cell growth through the mTOR signaling pathway in rat intestinal epithelial cells. Biochem Biophys Res Commun 326:174–180

    Article  PubMed  CAS  Google Scholar 

  • Naomoto Y, Yamatsuji T, Shigemitsu K et al (2005) Rational role of amino acids in intestinal epithelial cells. Int J Mol Med 16:201–204

    PubMed  CAS  Google Scholar 

  • Noiri E, Peresleni T, Srivastava N et al (1996) Nitric oxide is necessary for a switch from stationary to locomoting phenotype in epithelial cells. Am J Physiol 270:C794–C802

    PubMed  CAS  Google Scholar 

  • Noiri E, Lee E, Testa J et al (1998) Podokinesis in endothelial cell migration: role of nitric oxide. Am J Physiol 274:C236–C244

    PubMed  CAS  Google Scholar 

  • Novak F, Heyland DK, Avenell A et al (2002) Glutamine supplementation in serious illness: a systematic review of the evidence. Crit Care Med 30:2022–2029

    Article  PubMed  CAS  Google Scholar 

  • O’Dwyer ST, Smith RJ, Hwang TL, Wilmore DW (1989) Maintenance of small bowel mucosa with glutamine-enriched parenteral nutrition. J Parenter Enteral Nutr 13:579–585

    Article  Google Scholar 

  • Palii SS, Kays CE, Deval C et al. (2008) Specificity of amino acid regulated gene expression: analysis of genes subjected to either complete or single amino acid deprivation. Amino Acids. doi: 10.1007/s00726-008-0199-2

  • Papaconstantinou HT, Chung DH, Zhang W et al (2000) Prevention of mucosal atrophy: role of glutamine and caspases in apoptosis in intestinal epithelial cells. J Gastrointest Surg 4:416–423

    Article  PubMed  CAS  Google Scholar 

  • Peng ZY, Serkova NJ, Kominsky DJ et al (2006) Glutamine-mediated attenuation of cellular metabolic dysfunction and cell death after injury is dependent on heat shock factor-1 expression. J Parenter Enteral Nutr 30:373–378

    Article  CAS  Google Scholar 

  • Phanvijhitsiri K, Musch MW, Ropeleski MJ, Chang EB (2006) Heat induction of heat shock protein 25 requires cellular glutamine in intestinal epithelial cells. Am J Physiol Cell Physiol 291:C290–C299

    Article  PubMed  CAS  Google Scholar 

  • Poindexter BB, Ehrenkranz RA, Stoll BJ et al (2003) Effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants. Am J Clin Nutr 77:737–743

    PubMed  CAS  Google Scholar 

  • Potsic B, Holliday N, Lewis P et al (2002) Glutamine supplementation and deprivation: effect on artificially reared rat small intestinal morphology. Pediatr Res 52:430–436

    PubMed  CAS  Google Scholar 

  • Rhoads JM, Keku EO, Quinn J et al (1991) l-Glutamine stimulates jejunal sodium and chloride absorption in pig rotavirus enteritis. Gastroenterology 100:683–691

    PubMed  CAS  Google Scholar 

  • Rhoads JM, Argenzio RA, Chen W et al (1997) l-Glutamine stimulates intestinal cell proliferation and activates mitogen-activated protein kinases. Am J Physiol 272:G943–G953

    PubMed  CAS  Google Scholar 

  • Rhoads JM, Argenzio RA, Chen W et al (2000) Glutamine metabolism stimulates intestinal cell MAPKs by a cAMP-inhibitable, Raf-independent mechanism. Gastroenterology 118:90–100

    Article  PubMed  CAS  Google Scholar 

  • Rhoads JM, Chen W, Gookin J et al (2004) Arginine stimulates intestinal cell migration through a focal adhesion kinase dependent mechanism. Gut 53:514–522

    Article  PubMed  CAS  Google Scholar 

  • Rhoads JM, Niu X, Odle J, Graves LM (2006) Role of mTOR signaling in intestinal cell migration. Am J Physiol Gastrointest Liver Physiol 291:G510–G517

    Article  PubMed  CAS  Google Scholar 

  • Rhoads JM, Corl BA, Harrell R et al (2007) Intestinal ribosomal p70(s6k) signaling is increased in piglet rotavirus enteritis. Am J Physiol Gastrointest Liver Physiol 292:G913–G922

    Article  PubMed  CAS  Google Scholar 

  • Rhoads JM, Liu Y, Niu X et al (2008) Arginine stimulates cdx2-transformed intestinal epithelial cell migration via a mechanism requiring both nitric oxide and phosphorylation of p70 s6kinase. J Nutr 138:1652–1657

    PubMed  CAS  Google Scholar 

  • Ropeleski MJ, Riehm J, Baer KA et al (2005) Anti-apoptotic effects of l-glutamine-mediated transcriptional modulation of the heat shock protein 72 during heat shock. Gastroenterology 129:170–184

    Article  PubMed  CAS  Google Scholar 

  • Sato N, Moore FA, Kone BC et al (2006) Differential induction of PPAR-gamma by luminal glutamine and iNOS by luminal arginine in the rodent postischemic small bowel. Am J Physiol Gastrointest Liver Physiol 290:G616–G623

    Article  PubMed  CAS  Google Scholar 

  • Seth A, Basuroy S, Sheth P, Rao RK (2004) l-Glutamine ameliorates acetaldehyde-induced increase in paracellular permeability in Caco-2 cell monolayer. Am J Physiol Gastrointest Liver Physiol 287:G510–G517

    Article  PubMed  CAS  Google Scholar 

  • Siu F, Bain PJ, LeBlanc-Chaffin R et al (2002) ATF4 is a mediator of the nutrient-sensing response pathway that activates the human asparagine synthetase gene. J Biol Chem 277:24120–24127

    Article  PubMed  CAS  Google Scholar 

  • Stebbing JF, Brading AF, Mortensen NJ (1996) Nitrergic innervation and relaxant response of rectal circular smooth muscle. Dis Colon Rectum 39:294–299

    Article  PubMed  CAS  Google Scholar 

  • Stoll B, Burrin DG (2006) Measuring splanchnic amino acid metabolism in vivo using stable isotopic tracers. J Anim Sci 84(Suppl):E60–E72

    PubMed  Google Scholar 

  • Suryawan A, O’Connor PMJ, Bush JA et al. (2008) Differential regulation of protein synthesis by amino acids and insulin in peripheral and visceral tissues of neonatal pigs. Amino Acids. doi:10.1007/s00726-008-0149-z

  • Tan BE, Yin YL, Liu ZQ et al. (2008) Dietary L-arginine supplementation increases muscle gain and reduces body fat mass in growing-finishing pigs. Amino Acids. doi:10.1007/s00726-008-0148-0

  • Uehara K, Takahashi T, Fujii H et al (2005) The lower intestinal tract-specific induction of heme oxygenase-1 by glutamine protects against endotoxemic intestinal injury. Crit Care Med 33:381–390

    Article  PubMed  CAS  Google Scholar 

  • Wang WW, Qiao SY, Li DF (2008a) Amino acids and gut function. Amino Acids. doi:10.1007/s00726-008-0152-4

  • Wang JJ, Chen LX, Li P et al (2008b) Gene expression is altered in piglet small intestine by weaning and dietary glutamine supplementation. J Nutr 138:1025–1032

    PubMed  CAS  Google Scholar 

  • Wang JJ, Wu G, Zhou HJ, Wang FL (2008c) Emerging technologies for amino acid nutrition research in the post-genome era. Amino Acids. doi:10.1007/s00726-008-0193-8

  • Windmueller HG, Spaeth AE (1978) Identification of ketone bodies and glutamine as the major respiratory fuels in vivo for postabsorptive rat small intestine. J Biol Chem 253:69–76

    PubMed  CAS  Google Scholar 

  • Windmueller HG, Spaeth AE (1980) Respiratory fuels and nitrogen metabolism in vivo in small intestine of fed rats. Quantitative importance of glutamine, glutamate, and aspartate. J Biol Chem 255:107–112

    PubMed  CAS  Google Scholar 

  • Wischmeyer PE, Musch MW, Madonna MB et al (1997) Glutamine protects intestinal epithelial cells: role of inducible HSP70. Am J Physiol 272:G879–G884

    PubMed  CAS  Google Scholar 

  • Wischmeyer PE, Kahana M, Wolfson R et al (2001) Glutamine induces heat shock protein and protects against endotoxin shock in the rat. J Appl Physiol 90:2403–2410

    PubMed  CAS  Google Scholar 

  • Wu G (1998) Intestinal mucosal amino acid catabolism. J Nutr 128:1249–1252

    PubMed  CAS  Google Scholar 

  • Wu G, Knabe DA (1994) Free and protein-bound amino acids in sow’s colostrum and milk. J Nutr 124:415–424

    PubMed  CAS  Google Scholar 

  • Wu G, Knabe DA (1995) Arginine synthesis in enterocytes of neonatal pigs. Am J Physiol Regul Integr Comp Physiol 269:R621–R629

    CAS  Google Scholar 

  • Wu G, Meininger CJ (2000) Arginine nutrition and cardiovascular function. J Nutr 130:2626–2629

    PubMed  CAS  Google Scholar 

  • Wu G, Morris SM Jr (1998) Arginine metabolism: nitric oxide and beyond. Biochem J 336:1–17

    PubMed  CAS  Google Scholar 

  • Wu G, Knabe DA, Yan W, Flynn NE (1995) Glutamine and glucose metabolism in enterocytes of neonatal pigs. Am J Physiol Regul Integr Comp Physiol 268:R334–R342

    CAS  Google Scholar 

  • Wu G, Bazer FW, Tuo W, Flynn SP (1996a) Unusual abundance of arginine and ornithine in porcine allantoic fluid. Biol Reprod 54:1261–1265

    Article  PubMed  CAS  Google Scholar 

  • Wu G, Meier SA, Knabe DA (1996b) Dietary glutamine supplementation prevents jejunal atrophy in weaned pigs. J Nutr 126:2578–2584

    PubMed  CAS  Google Scholar 

  • Wu G, Haynes TE, Li H et al (2001) Glutamine metabolism to glucosamine is necessary for glutamine inhibition of endothelial nitric oxide synthesis. Biochem J 353:245–252

    Article  PubMed  CAS  Google Scholar 

  • Wu G, Bazer FW, Davis TA et al (2007a) Important roles for the arginine family of amino acids in swine nutrition and production. Livest Sci 112:8–22

    Article  Google Scholar 

  • Wu G, Bazer FW, Cudd TA et al (2007b) Pharmacokinetics and safety of arginine supplementation in animals. J Nutr 137:1673S–1680S

    PubMed  CAS  Google Scholar 

  • Wu G, Bazer FW, Datta S et al (2008a) Proline metabolism in the conceptus: implications for fetal growth and development. Amino Acids 35:691–702

    Article  PubMed  CAS  Google Scholar 

  • Wu G, Bazer FW, Davis TA et al. (2008b) Arginine metabolism and nutrition in growth, health and disease. Amino Acids. doi: 10.1007/s00726-008-0210-y

  • Yang F, Wang JJ, Li XJ et al (2007) Two-dimensional gel electrophoresis and mass spectrometry analysis of interactions between Lactobacillus Fermentum I5007 and intestinal epithelial cells. Electrophoresis 28:4330–4339

    Article  PubMed  CAS  Google Scholar 

  • Zamora SA, Amin HJ, McMillan DD et al (1997) Plasma l-arginine concentrations in premature infants with necrotizing enterocolitis. J Pediatr 131:226–232

    Article  PubMed  CAS  Google Scholar 

  • Zamora R, Bryan NS, Boyle P et al (2005) Nitrosative stress in an animal model of necrotizing enterocolitis. Free Radic Biol Med 39:1428–1437

    Article  PubMed  CAS  Google Scholar 

  • Ziegler TR, Mantell MP, Chow JC et al (1996) Gut adaptation and the insulin-like growth factor system: regulation by glutamine and IGF-I administration. Am J Physiol 271:G866–G875

    PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported, in part, by grants from National Institutes of Health (1RO3-DK57774) and USDA (NRCGIP 02092) (JMR), the Ochsner Clinic Foundation (JMR), The University of Texas Medical School at Houston (JMR), National Research Initiative Competitive Grants (2008-35206-18764, and 2008-35203-19120) from the USDA Cooperative State Research, Education, and Extension Service (GW), and Texas AgriLife Research (H-8200) (GW). The authors thank Drs. Teresa A. Davis and Nick E. Flynn for helpful comments on this paper.

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  1. Department of Pediatrics, University of Texas Medical School at Houston, Houston, TX, 77030, USA

    J. Marc Rhoads

  2. Department of Animal Science, Texas A&M University, College Station, TX, 77843, USA

    Guoyao Wu

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Correspondence to J. Marc Rhoads.

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Marc Rhoads, J., Wu, G. Glutamine, arginine, and leucine signaling in the intestine. Amino Acids 37, 111–122 (2009). https://doi.org/10.1007/s00726-008-0225-4

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