Abstract
OBJECTIVE: The authors determined the effects of alanyl-glutamine-supplemented total parenteral nutrition (TPN) on mucosal metabolism, integrity, and permeability of the small intestine in rats. METHODS: Male Sprague-Dawley rats were randomized to receive TPN supplemented with a conventional amino acids mixture (STD group) or the same solution supplemented with alanyl-glutamine; both solutions were isocaloric and isonitrogenous. On the seventh day of TPN, D-xylose and fluorescein isothiocyanate (FITC)-dextran were administered orally. One hour later, superior mesenteric vein (SMV) D-xylose and plasma FITC-dextran concentration were measured. Intestinal blood flow and calculated intestinal substrates flux were measured with ultrasonic transit time flowmetery. RESULTS: Plasma FITC-dextran increased significantly in the STD group. Intestinal blood flow and SMV D-xylose concentration did not differ between the groups. Mucosa weight, villus height, mucosal wall thickness, mucosal protein, and DNA and RNA content in jejunal mucosa were significantly increased in the alanyl-glutamine group. Jejunal mucosal glutaminase activity and net intestinal uptake of glutamine (glutamine flux) were significantly higher in the alanyl-glutamine group as compared with the STD group. CONCLUSION: Addition of alanyl-glutamine dipeptide to the TPN solution improves intestinal glutamine metabolism and prevents mucosal atrophy and deterioration of permeability.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alverdy J. C., Aoys E., Moss G. S. Total parenteral nutrition promotes bacterial translocation from the gut. Surgery. 1988 Aug;104(2):185–190. [PubMed] [Google Scholar]
- Bloom S. R. Gut hormones in adaptation. Gut. 1987;28 (Suppl):31–35. doi: 10.1136/gut.28.suppl.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
- Brandl M., Sailer D., Langer K., Engelhardt A., Kleinhenz H., Adibi S. A., Fekl W. Parenteral nutrition with an amino acid solution containing a mixture of dipeptides. Evidence for efficient utilization of dipeptides in man. Beitr Infusionther Klin Ernahr. 1987;17:103–116. [PubMed] [Google Scholar]
- Buts J. P., Morin C. L., Roy C. C., Weber A., Bonin A. One-hour blood xylose test: a reliable index of small bowel function. J Pediatr. 1978 May;92(5):729–733. doi: 10.1016/s0022-3476(78)80138-3. [DOI] [PubMed] [Google Scholar]
- Cameron I. L., Pavlat W. A., Urban E. Adaptive responses to total intravenous feeding. J Surg Res. 1974 Jul;17(1):45–52. doi: 10.1016/0022-4804(74)90167-x. [DOI] [PubMed] [Google Scholar]
- Curthoys N. P., Lowry O. H. The distribution of glutaminase isoenzymes in the various structures of the nephron in normal, acidotic, and alkalotic rat kidney. J Biol Chem. 1973 Jan 10;248(1):162–168. [PubMed] [Google Scholar]
- Eastwood G. L. Small bowel morphology and epithelial proliferation in intravenously alimented rabbits. Surgery. 1977 Nov;82(5):613–620. [PubMed] [Google Scholar]
- Eberts T. J., Sample R. H., Glick M. R., Ellis G. H. A simplified, colorimetric micromethod for xylose in serum or urine, with phloroglucinol. Clin Chem. 1979 Aug;25(8):1440–1443. [PubMed] [Google Scholar]
- Fox A. D., Kripke S. A., Berman J. M., McGintey R. M., Settle R. G., Rombeau J. L. Dexamethasone administration induces increased glutaminase specific activity in the jejunum and colon. J Surg Res. 1988 Apr;44(4):391–396. doi: 10.1016/0022-4804(88)90181-3. [DOI] [PubMed] [Google Scholar]
- Fürst P., Albers S., Stehle P. Availability of glutamine supplied intravenously as alanylglutamine. Metabolism. 1989 Aug;38(8 Suppl 1):67–72. doi: 10.1016/0026-0495(89)90145-5. [DOI] [PubMed] [Google Scholar]
- Goodlad R. A., Lenton W., Ghatei M. A., Adrian T. E., Bloom S. R., Wright N. A. Proliferative effects of 'fibre' on the intestinal epithelium: relationship to gastrin, enteroglucagon and PYY. Gut. 1987;28 (Suppl):221–226. doi: 10.1136/gut.28.suppl.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grant J. P., Snyder P. J. Use of L-glutamine in total parenteral nutrition. J Surg Res. 1988 May;44(5):506–513. doi: 10.1016/0022-4804(88)90155-2. [DOI] [PubMed] [Google Scholar]
- Hindmarsh J. T. Xylose absorption and its clinical significance. Clin Biochem. 1976 Jun;9(3):141–143. doi: 10.1016/s0009-9120(76)80036-7. [DOI] [PubMed] [Google Scholar]
- Iiboshi Y., Nezu R., Kennedy M., Fujii M., Wasa M., Fukuzawa M., Kamata S., Takagi Y., Okada A. Total parenteral nutrition decreases luminal mucous gel and increases permeability of small intestine. JPEN J Parenter Enteral Nutr. 1994 Jul-Aug;18(4):346–350. doi: 10.1177/014860719401800412. [DOI] [PubMed] [Google Scholar]
- Johnson L. R., Copeland E. M., Dudrick S. J., Lichtenberger L. M., Castro G. A. Structural and hormonal alterations in the gastrointestinal tract of parenterally fed rats. Gastroenterology. 1975 May;68(5 Pt 1):1177–1183. [PubMed] [Google Scholar]
- Katz M. L., Bergman E. N. Simultaneous measurements of hepatic and portal venous blood flow in the sheep and dog. Am J Physiol. 1969 Apr;216(4):946–952. doi: 10.1152/ajplegacy.1969.216.4.946. [DOI] [PubMed] [Google Scholar]
- Li S. J., Nussbaum M. S., McFadden D. W., Zhang F. S., LaFrance R. J., Dayal R., Fischer J. E. Addition of L-glutamine to total parenteral nutrition and its effects on portal insulin and glucagon and the development of hepatic steatosis in rats. J Surg Res. 1990 May;48(5):421–426. doi: 10.1016/0022-4804(90)90006-n. [DOI] [PubMed] [Google Scholar]
- Lo C. W., Walker W. A. Changes in the gastrointestinal tract during enteral or parenteral feeding. Nutr Rev. 1989 Jul;47(7):193–198. doi: 10.1111/j.1753-4887.1989.tb02837.x. [DOI] [PubMed] [Google Scholar]
- Menzies I. S., Laker M. F., Pounder R., Bull J., Heyer S., Wheeler P. G., Creamer B. Abnormal intestinal permeability to sugars in villous atrophy. Lancet. 1979 Nov 24;2(8152):1107–1109. doi: 10.1016/s0140-6736(79)92507-8. [DOI] [PubMed] [Google Scholar]
- O'Dwyer S. T., Smith R. J., Hwang T. L., Wilmore D. W. Maintenance of small bowel mucosa with glutamine-enriched parenteral nutrition. JPEN J Parenter Enteral Nutr. 1989 Nov-Dec;13(6):579–585. doi: 10.1177/0148607189013006579. [DOI] [PubMed] [Google Scholar]
- Pinkus L. M., Windmueller H. G. Phosphate-dependent glutaminase of small intestine: localization and role in intestinal glutamine metabolism. Arch Biochem Biophys. 1977 Aug;182(2):506–517. doi: 10.1016/0003-9861(77)90531-8. [DOI] [PubMed] [Google Scholar]
- Prasad A. S., DuMouchelle E., Koniuch D., Oberleas D. A simple fluorometric method for the determination of RNA and DNA in tissues. J Lab Clin Med. 1972 Oct;80(4):598–602. [PubMed] [Google Scholar]
- Purandare S., Offenbartl K., Weström B., Bengmark S. Increased gut permeability to fluorescein isothiocyanate-dextran after total parenteral nutrition in the rat. Scand J Gastroenterol. 1989 Aug;24(6):678–682. doi: 10.3109/00365528909093108. [DOI] [PubMed] [Google Scholar]
- Riecken E. O., Stallmach A., Zeitz M., Schulzke J. D., Menge H., Gregor M. Growth and transformation of the small intestinal mucosa--importance of connective tissue, gut associated lymphoid tissue and gastrointestinal regulatory peptides. Gut. 1989 Nov;30(11):1630–1640. doi: 10.1136/gut.30.11.1630. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sarantos P., Abouhamze A., Souba W. W. Glucocorticoids regulate intestinal glutaminase expression. Surgery. 1992 Aug;112(2):278–283. [PubMed] [Google Scholar]
- Singh G., Chaudry K. I., Morrison M. H., Chaudry I. H. Tumor necrosis factor depresses gut absorptive function. Circ Shock. 1993 Apr;39(4):279–284. [PubMed] [Google Scholar]
- Souba W. W. Glutamine: a key substrate for the splanchnic bed. Annu Rev Nutr. 1991;11:285–308. doi: 10.1146/annurev.nu.11.070191.001441. [DOI] [PubMed] [Google Scholar]
- Souba W. W., Klimberg V. S., Plumley D. A., Salloum R. M., Flynn T. C., Bland K. I., Copeland E. M., 3rd The role of glutamine in maintaining a healthy gut and supporting the metabolic response to injury and infection. J Surg Res. 1990 Apr;48(4):383–391. doi: 10.1016/0022-4804(90)90080-l. [DOI] [PubMed] [Google Scholar]
- Souba W. W., Scott T. E., Wilmore D. W. Intestinal consumption of intravenously administered fuels. JPEN J Parenter Enteral Nutr. 1985 Jan-Feb;9(1):18–22. doi: 10.1177/014860718500900118. [DOI] [PubMed] [Google Scholar]
- Souba W. W., Smith R. J., Wilmore D. W. Glutamine metabolism by the intestinal tract. JPEN J Parenter Enteral Nutr. 1985 Sep-Oct;9(5):608–617. doi: 10.1177/0148607185009005608. [DOI] [PubMed] [Google Scholar]
- Stehle P., Zander J., Mertes N., Albers S., Puchstein C., Lawin P., Fürst P. Effect of parenteral glutamine peptide supplements on muscle glutamine loss and nitrogen balance after major surgery. Lancet. 1989 Feb 4;1(8632):231–233. doi: 10.1016/s0140-6736(89)91254-3. [DOI] [PubMed] [Google Scholar]
- Tamada H., Nezu R., Imamura I., Matsuo Y., Takagi Y., Kamata S., Okada A. The dipeptide alanyl-glutamine prevents intestinal mucosal atrophy in parenterally fed rats. JPEN J Parenter Enteral Nutr. 1992 Mar-Apr;16(2):110–116. doi: 10.1177/0148607192016002110. [DOI] [PubMed] [Google Scholar]
- Thompson J. C. Humoral control of gut function. Am J Surg. 1991 Jan;161(1):6–18. doi: 10.1016/0002-9610(91)90354-g. [DOI] [PubMed] [Google Scholar]
- Travis S., Menzies I. Intestinal permeability: functional assessment and significance. Clin Sci (Lond) 1992 May;82(5):471–488. doi: 10.1042/cs0820471. [DOI] [PubMed] [Google Scholar]
- Weström B. R., Svendsen J., Ohlsson B. G., Tagesson C., Karlsson B. W. Intestinal transmission of macromolecules (BSA and FITC-labelled dextrans) in the neonatal pig. Influence of age of piglet and molecular weight of markers. Biol Neonate. 1984;46(1):20–26. doi: 10.1159/000242028. [DOI] [PubMed] [Google Scholar]
- Wilmore D. W., Smith R. J., O'Dwyer S. T., Jacobs D. O., Ziegler T. R., Wang X. D. The gut: a central organ after surgical stress. Surgery. 1988 Nov;104(5):917–923. [PubMed] [Google Scholar]
- Windmueller H. G., Spaeth A. E. Respiratory fuels and nitrogen metabolism in vivo in small intestine of fed rats. Quantitative importance of glutamine, glutamate, and aspartate. J Biol Chem. 1980 Jan 10;255(1):107–112. [PubMed] [Google Scholar]
- Windmueller H. G., Spaeth A. E. Uptake and metabolism of plasma glutamine by the small intestine. J Biol Chem. 1974 Aug 25;249(16):5070–5079. [PubMed] [Google Scholar]
- van der Hulst R. R., van Kreel B. K., von Meyenfeldt M. F., Brummer R. J., Arends J. W., Deutz N. E., Soeters P. B. Glutamine and the preservation of gut integrity. Lancet. 1993 May 29;341(8857):1363–1365. doi: 10.1016/0140-6736(93)90939-e. [DOI] [PubMed] [Google Scholar]