Skip to main content

Glycyl-glutamine-supplemented long-term total parenteral nutrition selectively improves structure and function in heterotopic small-bowel autotransplantation in the pig


Marked atrophy and impaired absorptive and barrier function occur in transplanted small intestinal graft during total parenteral nutrition (TPN), TPN is required by all the patients after small bowel transplantation (SBT). Glutamine (Gln) is a conditional indispensable amino acid that is not included in regimens for parenteral nutrition because of its chemical instability in aqueous solution. Glutamine-containing dipeptide, however, is heat-stable. With this study, we determine whether the glycyl-glutamine-supplemented long-term TPN improves mucosal structure and function in heterotopic transplanted small intestinal graft in the pig. Ten outbred pigs, randomly divided into two groups, underwent heterotopic small bowel autotransplantation. In the STPN group, the animals received standard TPN without glycyl-glutamine (Gly-Gln) and in the GTPN group, the animals received isonitrogenous (0.3g kg day–1) and isocalories (nonprotein calories, 30 kcal kg day–1) TPN with Gly-Gln (3% Gln) for 28 days. At the end of TPN, there was no significant difference in the body weight loss between two groups (P>0.05). The mucosal contents of Gln and protein were significantly higher in the GTPN group than in the STPN group (P<0.05). The mucosal disaccharidase activities in the homogenate of the graft mucosa of the GTPN group were significantly higher than that of the STPN group (P<0.05). The villous height, surface area, mucosal thickness were significantly higher in the GTPN group than in the STPN group (P<0.05). There was no significant difference in crypt depth between the two groups (P>0.05). These results suggest that glycyl-glutamine-supplemented long-term TPN improves graft mucosal structure in heterotopic autotransplanted small bowel grafts in the pig. Long-term (4 weeks) TPN supplemented with Gln could alleviate small intestinal graft atrophy, but could not completely eliminate atrophy.

This is a preview of subscription content, access via your institution.

Fig. 1.
Fig. 2.


  1. 1.

    Todo S, Reyes J, Furokawa H, et al. Outcome analysis of 71 clinical intestinal transplantation. Ann Surg 1995; 220:270.

    Google Scholar 

  2. 2.

    Grant D. Intestinal transplantation: 1997 report of the international registry. Transplantation 1999; 67:1061.

    Google Scholar 

  3. 3.

    Rovera GM, Abu-Elmgd K, Huston WR, et al. Long-term nutrition monitoring after clinical intestinal transplantation. Transplant Proc 1998; 32:2515.

    Article  Google Scholar 

  4. 4.

    Li YS, Li JS, Jiang JW, et al. Glycyl-glutamine-enriched long-term total parenteral nutrition attenuates bacterial translocation following small bowel transplantation in the pig. J Surg Res 1999; 82:106.

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Sitrin HS, Bryant M, Ellis LM. Species differences in TPN-induced intestinal villous atrophy (abstract). JPEN J Parenter Enteral Nutr 1992; 16 [Suppl]:30.

    Google Scholar 

  6. 6.

    Guedon C, Schmitz J, Lerebours E, et al. Decreased bush borde hydrolase activities without gross morphologic changes in humans intestinal mucosa after prolonged total parenteral nutrition of adults. Gastroenterology 1986; 90:373.

    CAS  PubMed  Google Scholar 

  7. 7.

    Buchman AL, Moukarzei AA, Bhuta S, et al. Parenteral nutrition associated with intestinal morphologic and functional changes in humans. JPEN J Parenter Enteral Nutr 1995; 19:453.

    CAS  PubMed  Google Scholar 

  8. 8.

    Ziegler TR, Bazargan N, Leader LM, et al. Glutamine and the gastrointestinal tract. Curr Opin Clin Nutr Metab Care 2000; 3:355.

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    Furst P, Albers S, Stehle P. Availability of glutamine supplied intravenous as alanylglutamine. Metabolism 1989; 38:67.

    CAS  Google Scholar 

  10. 10.

    Zhang W, Frankel WL, Singh A, et al. Improvement of structure and function in orthotopic small bowel transplantation in the rat by glutamine. Transplantation 1993; 56:512.

    CAS  PubMed  Google Scholar 

  11. 11.

    Yagi M, Sakamoto K, Hasebe K, et al. Effect of glutamine-enriched diet on small bowel allograft during immunosuppression therapy. Nutrition 1997; 13:778.

    Article  CAS  PubMed  Google Scholar 

  12. 12.

    Burrin DG, Shulman RJ, Langston C, et al. Supplemented alanyl-glutamine organ growth, and nitrogen metabolism in neonatal pig fed by glutamine. JPEN J Parenter Enteral Nutr 1994; 18:313.

    CAS  PubMed  Google Scholar 

  13. 13.

    Li YS, Li JS, Li N. The technique of small bowel transplantation in the pig. J Nanjing Univ 1995; 31:5

    Google Scholar 

  14. 14.

    Lowry OH. Protein measurement with the folin-phenol regent. J Biol Chem 1951; 193:265

    CAS  Google Scholar 

  15. 15.

    Liu FN, Li JS, Li YS, et al. Plasma glutamine level monitor with high performance liquid chromatography for patients infusing glutamine after small bowel transplantation . China J Chromatogr 1997; 15:445.

    Google Scholar 

  16. 16.

    Dalqvist A. A model for assay of intestinal disaccharidase. Ann Biochem 1965; 7:18.

    Google Scholar 

  17. 17.

    Eberts JL, Sample KHB, Glick MR. et al. A simplified colometric micromethod for xylose in serum or urine with photoroglocinol. Clin Chem 1979; 25:1440.

    CAS  PubMed  Google Scholar 

  18. 18.

    Furst P. A thirty-year odyssey in nitrogen metabolism: from ammonium to dipeptide. JPEN J Parenter Enteral Nutr 2000; 24:197.

    CAS  PubMed  Google Scholar 

  19. 19.

    Furst P, Pogan K, Stehle P. Glutamine dipeptides in clinical nutrition. Nutrition 1997; 13:731.

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    MacBurney M, Young LS, Ziegler TR. et al. Cost-evaluation of glutamine-supplemented parenteral nutrition in adult bone marrow transplant patients. J Am Diet Assoc 1994; 94:1263.

    CAS  PubMed  Google Scholar 

  21. 21.

    Petersson B, van der Decken A, Vinna E, et al. Long-term effect of postoperative nutrition supplemented with glycylglutamine on subjective fatigue and muscle protein synthesis. Br J Surg 1994; 81:1520.

    CAS  PubMed  Google Scholar 

  22. 22.

    Ziegle TR, Bye RL, Persinger RL, et al. Effect of glutamine supplementation on circulating lymphocytes after bone marrow transplantation: a pilot study. Am J Med Sci 1998; 318:4.

    Google Scholar 

  23. 23.

    Schroder J, Kahlke V, Fandrich F, et al. Glutamine dipeptide-supplemented parenteral nutrition reverse gut mucosal structure and interleukin-6 release of rat intestine mononuclear cells after hemorrhage shock. Shock 1998; 10:26.

    CAS  PubMed  Google Scholar 

  24. 24.

    Nemoto A, Krajack A, Suzuki T, et al. Glutamine metabolism of intestinal grafts; influence on mucosal injury by prolonged preserved and transplantation. Transplant Proc 1996; 28:2545.

    CAS  PubMed  Google Scholar 

  25. 25.

    Spittler A, Sautner T, Gornikiewicz A, et al. Postoperative glycyl-glutamine infusion reduces immunosuppression: partial prevention of the surgery induced decrease in HLA-DR expression on monocytes. Clin Nutr 2001; 20:37.

    Article  CAS  PubMed  Google Scholar 

  26. 26.

    Exner R, Tamandl D, Goetzinger P, et al. Perioperative GLY-GLN infusion diminished the surgery-induced period of immunosuppression:accelerated restoration of the lipopolysaccharide-stimulated tumor necrosis factor-alpha response. Ann Surg 2003; 237:110.

    Article  PubMed  Google Scholar 

  27. 27.

    Sarr MG. Motility and absorption in the transplanted gut. Transplant Proc 1996; 28:2535.

    Google Scholar 

  28. 28.

    Frankel WL, Zhang W, Afonso J, et al. Glutamine enhancement of structure and function in transplanted small intestine in the rat. JPEN J Parenter Enteral Nutr 1993; 17:47.

    CAS  PubMed  Google Scholar 

  29. 29.

    Rossi TM, Lee PC, Young C, et al. Small intestine mucosa changes, including epithelial cell proliferative activity, of children receiving total parenteral nutrition. Dig Dis Sci 1993; 38:1608.

    CAS  PubMed  Google Scholar 

  30. 30.

    van der Hulst RRW, von Meyerfeldt M, Deutz NEP, et al. The effect of glutamine administration on intestinal glutamine contents. J Surg Res 1996; 61:30.

    Article  PubMed  Google Scholar 

  31. 31.

    van der Hulst RRW, von Meyerfeldt M, Tiebosch A, et al. Glutamine and intestinal immune cells and humans. JPEN J Parenter Enteral Nutr 1997; 21:310.

    Google Scholar 

  32. 32.

    Platell C, McCauley R, McCulloch R, Hall J. The influence of parenteral glutamine and branched chain acid on total parenteral nutrition-induced atrophy of gut. JPEN J Parenter Enteral Nutr 1993; 17:348

    Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Yousheng Li.

About this article

Cite this article

Li, Y., Li, J., Jiang, J. et al. Glycyl-glutamine-supplemented long-term total parenteral nutrition selectively improves structure and function in heterotopic small-bowel autotransplantation in the pig. Transpl Int 16, 866–871 (2002).

Download citation


  • Glutaine
  • Small intestine transplantation
  • Total parenteral nutrition