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Intestinal Growth Adaptation and Glucagon-like Peptide 2 in Rats with Ileal–Jejunal Transposition or Small Bowel Resection

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Abstract

Glucagon-like peptide 2 (GLP-2), produced by enteroendocrine L-cells, regulates intestinal growth. This study investigates circulating and intestinal GLP-2 levels in conditions with altered L-cell exposure to nutrients. Rats were allocated to the following experimental groups: ileal–jejunal transposition, resection of the proximal or distal half of the small intestine, and appropriate sham-operated controls. After two weeks, ileal–jejunal transposition led to pronounced growth of the transposed segment and also of the remaining intestinal segments. Plasma GLP-2 levels increased twofold, whereas GLP-2 levels in the intestinal segments were unchanged. In resected rats with reduced intestinal capacity, adaptive small bowel growth was more pronounced following proximal resection than distal small bowel resection. Circulating GLP-2 levels increased threefold in proximally resected animals, and twofold in the distally resected group. Tissue GLP-2 levels were unchanged in resected rats. The data indicate that transposition of a distal part of the small intestine, and thereby exposure of L cells to a more nutrient-rich chyme, leads to intestinal growth. The adaptive intestinal growth is associated with increased plasma levels of GLP-2, and GLP-2 seems to act in an endocrine as well as a paracrine manner.

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REFRENCES

  1. Dowling RH, Booth CC: Structural and functional changes following small intestinal resection in the rat. Clin Sci 32:39–149, 1967

    Google Scholar 

  2. Drucker DJ, Ehrlich P, Asa SL, Brubaker PL: Induction of intestinal epithelial proliferation by glucagon-like peptide 2. Proc Natl Acad Sci USA 93:7911–7916, 1996

    Google Scholar 

  3. Tsai C, Hill M, Asa SL, Brubaker PL, Drucker DJ: Intestinal growth properties of glucagon-like peptide-2 in mice. Am J Physiol 273(Endocrinol Metab):E77–E84, 1997

    Google Scholar 

  4. Tsai C, Hill M, Drucker DJ: Biological determinants of intestinotrophic properties of GLP-2 in vivo. Am J Physiol 272(Gastrointest Liver Physiol):G662–G668, 1997

    Google Scholar 

  5. Wood JG, Hoang HD, Bussjaeger LJ, Solomon TE: Neurotensin stimulates growth of small intestine in rats. Am J Physiol 255(Gastrointest Liver Physiol):G813–G817, 1988

    Google Scholar 

  6. Evers BM, Izukura M, Townsend CM, Uchida T, Thompson JC: Differential effects of gut hormones on pancreatic and intestinal growth during administration of an elemental diet. Ann Surg 211:630–638, 1990

    Google Scholar 

  7. Vanderhoof JA, McCusker RH, Clark R, Mohammadpour R, Blackwood DJ, Harty RF, Park JHY: Truncated and native insulinlike growth factor I enhance mucosal adaptation after jejunoileal resection. Gastroenterology 102:1949–1956, 1992

    Google Scholar 

  8. Ulshen MH, Lyn-cook LE, Raasch RH: Effects of intraluminal epidermal growth factor on mucosal proliferation in the small intestine of adult rats. Gastroenterology 91:1134–1140, 1986

    Google Scholar 

  9. Dembinski A, Gregory H, Konturek SJ, Polanski M: Trophic action of epidermal growth factor on the pancreas and gastroduodenal mucosa of rats. J Physiol (London) 325:35–42, 1982

    Google Scholar 

  10. Taylor RG, Verity K, Fuller PJ: Ileal glucagon gene expression: ontogeny and response to massive small bowel resection. Gastroenterology 99:724–729, 1990

    Google Scholar 

  11. Fuller PJ, Beveridge DJ, Taylor RG: Ileal proglucagon gene expression in the rat: Characterization in intestinal adaptation using in situ hybridization. Gastroenterology 104:459–466, 1993

    Google Scholar 

  12. Ferri GL, Koopmans HS, Ghatei MA, Vezzadini P, Laboò G, Bloom SR, Polak JM: Ileal enteroglucagon cells after ilealduodenal transposition in the rat. Digestion 26:10–16, 1983

    Google Scholar 

  13. Al-Mukhtar MYT, Sagor GR, Ghatei MA, Bloom SR, Wright NA: The role of pancreaticobiliary secretions in intestinal adaptation after resection, and its relationship to plasma enteroglucagon. Br J Surg 70:398–400, 1983

    Google Scholar 

  14. Sagor GR, Ghatei MA, Al-Mukhtar MYT, Wright NA, Bloom SR: Evidence for a humoral mechanism after small intestinal resection. Exclusion of gastrin but not enteroglucagon. Gastroenterology 84:902–906, 1983

    Google Scholar 

  15. Bloom SR, Polak JM: The hormonal pattern of intestinal adaptation. Scand J Gastroenterol 17:93–103, 1982

    Google Scholar 

  16. Brubaker PL, Izzo A, Hill M, Drucker DJ: Intestinal function in mice with small bowel growth induced by glucagon-like peptide-2. Am J Physiol 272(Endocrinol Metab):E1050–E1058, 1997

    Google Scholar 

  17. Kato Y, Dahong Y, Schwartz MZ: Glucagonlike peptide-2 enhances small intestinal absorptive function and mucosal mass in vivo. J Pediatr Surg 34:18–21, 1999

    Google Scholar 

  18. Scott RB, Kirk D, MacNaughton WK, Meddings JB: GLP-2 augments the adaptive response to massive intestinal resection in rat. Am J Physiol 275(Gastrointest Liver Physiol):G911–G921, 1998

    Google Scholar 

  19. Drucker DJ, Yusta B, Boushey RP, DeForest L, Brubaker PL: Human (Gly2)GLP-2 reduces the severity of colonic injury in a murine model of experimental colitis. Am J Physiol 276(Gastrointest Liver Physiol):G79–G91, 1999

    Google Scholar 

  20. Chance WT, Foley-Nelson T, Thomas I, Balasubramaniam A: Prevention of parenteral nutrition-induced gut hypoplasia by coinfusion of glucagon-like peptide-2. Am J Physiol 273(Gastrointest Liver Physiol):G559–G563, 1997

    Google Scholar 

  21. Fischer KD, Dhanvantari S, Drucker DJ, Brubaker PL: Intestinal growth is associated with elevated levels of glucagon-like peptide 2 in diabetic rats. Am J Physiol 273(Endocrinol Metab):E815–E820, 1997

    Google Scholar 

  22. Thulesen J, Hartmann B, Nielsen C, Holst JJ, Poulsen SS: Diabetic intestinal growth adaptation and glucagon-like peptide 2 (GLP-2) in the rat. Effects of dietary fibres. Gut 45:672–678, 1999

    Google Scholar 

  23. Ørskov C, Holst JJ, Knuhtsen S, Baldissera FG, Poulsen SS, Nielsen OV: Glucagon-like peptides GLP-1 and GLP-2, predicted products of the glucagon gene, are secreted separately from pig small intestine but not pancreas. Endocrinology 119:1467–1475, 1986

    Google Scholar 

  24. Buhl T, Thim L, Ørskov C, Harling H, Holst JJ: Naturally occurring products of proglucagon 111-160 in the porcine and human small intestine. J Biol Chem 263:8621–8624, 1988

    Google Scholar 

  25. Bristol JB, Williamson RCN, Chir M: Nutrition, operations, and intestinal adaptation. JPEN 12:299–309, 1988

    Google Scholar 

  26. Hartmann B, Johnsen AH, Ørskov C, Adelhorst K, Thim L, Holst JJ: Structure, measurement and secretion of human glucagon-like peptide-2. Peptides 21:73–80, 2000

    Google Scholar 

  27. Tappenden KA, McBurney MI: Systemic short-chain fatty acids rapidly alter gastrointestinal structure, function, and expression of early response genes. Dig Dis Sci 43:1526–1536, 1998

    Google Scholar 

  28. Reimer RA, McBurney MI: Dietary fiber modulates intestinal proglucagon messenger ribonucleic acid and postprandial secretion of glucagon-like peptide-1 and insulin in rats. Endocrinology 137:3948–3956, 1996

    Google Scholar 

  29. Roberge JN, Brubaker PL: Secretion of proglucagon-derived peptides in response to intestinal luminal nutrients. Endocrinology 128:3169–3174, 1991

    Google Scholar 

  30. Jeppesen PB, Hartmann B, Hansen BS, Thulesen J, Holst JJ, Mortensen PB: Impaired meal-stimulated glucagon-like peptide-2 response in ileal resected short bowel patients with intestinal failure. Gut 45:559–563, 1999

    Google Scholar 

  31. Morin CL, Ling V, Bourassa D: Small intestine and colonic changes induced by a chemically defined diet. Dig Dis Sci 25:123–128, 1980

    Google Scholar 

  32. Drucker DJ, Shi Q, Crivici A, Summer-Smith M, Tavares W, Hill M, DeForest L, Cooper S, Brubaker PL: Regulation of the biological activity of glucagon-like peptide 2 in vivo by dipeptidyl peptidase IV. Nat Biotechnol 15:673–677, 1997

    Google Scholar 

  33. Holst JJ, Bersani M: Methods in Neurosciences, Vol 5. London, Academic Press, 1991, pp 3–22

    Google Scholar 

  34. Wøjdemann M, Wettergren A, Hartmann B, Holst JJ: Glucagon-like peptide-2 inhibits centrally antral motility in pigs. Scand J Gastroenterol 33:828–832, 1998

    Google Scholar 

  35. Johnson LR: Regulation of gastrointestinal mucosal growth. Physiol Rev 68:456–502, 1988

    Google Scholar 

  36. Levine GM, Deren JJ, Yezdimir E: Small-bowel resection. Oral intake is the stimulus for hyperplasia. Dig Dis Sci 7:542–546, 1976

    Google Scholar 

  37. Albert V, Young GP, Morton CL, Robinson P, Bhathal PS: Systemic factors are trophic in bypassed rat small intestine in the absence of luminal contents. Gut 31:311–316, 1990

    Google Scholar 

  38. Williamson RCN, Bauer FLR: Evidence for an enterotrophic hormone: Compensatory hyperplasia in defunctioned bowel. Br J Surg 65:736–739, 1978

    Google Scholar 

  39. Williamson RCN, Chir M, Buchholtz TW, Malt RA: Humoral stimulation of cell proliferation in small bowel after transection and resection in rat. Gastroenterology 75:249–254, 1978

    Google Scholar 

  40. Weser E, Babbitt J, Hoban M, Vandeventer A: Intestinal adaptation. Different growth responses to disaccharides compared with monosaccharides in rat small bowel. Gastroenterology 91:1521–1527, 1986

    Google Scholar 

  41. Sagor GR, Al-Mukhtar MYT, Ghatei MA, Wright NA, Bloom SR: The effect of altered lumnal nutrition on cellular proliferation and plasma concentrations of enteroglucagon and gastrin after small bowel resection in the rat. Br J Surg 69:14–18, 1982

    Google Scholar 

  42. Bloom SR, Besterman HS, Adrian TE, Christofides ND, Sarson DL, Mallinson CN, Pero A, Modigliani R: Gut hormone profile following resection of large and small bowel. Gastroenterology 76:1101, 1979 (abstract)

    Google Scholar 

  43. Mojsov S, Heinrich G, Wilson IB, Ravazzola M, Orci L, Habener JF: Preproglucagon gene expression in pancreas and intestine diversifies at the level of post-translational processing. J Biol Chem 261:11880–11889, 1986

    Google Scholar 

  44. George SK, Uttenthal LO, Ghiglione M, Bloom SR: Molecular forms of glucagon-like peptides in man. FEBS Lett 192:275–278, 1985

    Google Scholar 

  45. Holst JJ: Enteroglucagon. Annu Rev Physiol 59:257–271, 1997

    Google Scholar 

  46. Bloom SR: An enteroglucagon tumour. Gut 13:520–523, 1972

    Google Scholar 

  47. Gleeson MH, Bloom SR, Polak JM, Henry K, Dowling RH: Endocrine tumour in kidney affacting small bowel structure, motility, and absorptive function. Gut 12:773–782, 1971

    Google Scholar 

  48. Stevens FM, Flanagan RW, O'Gorman D, Buchanan KD: Glucagonoma syndrome demonstrating giant duodenal villi. Gut 25:784–791, 1984

    Google Scholar 

  49. White A, Kan K, Gray C, Oberts I, Ratcliffe JG: Multiple hormone secretion by a human pancreatic glucagonoma in culture. Regul Pept 11:335–345, 1985

    Google Scholar 

  50. Bloom SR, Royston CMS, Thomson JPS: Enteroglucagon release in the dumping syndrome. Lancet 2:789–791, 1972

    Google Scholar 

  51. Besterman HS, Bloom SR, Sarson DL, Blackburn AM, Johnson DI, Patel HR, Stewart JS, Modigliani R, Guerin S, Mallinson CN: Gut-hormone profile in caeliac disease. Lancet 1:785–788, 1978

    Google Scholar 

  52. Gregor M, Menge H, Stössel R, Riecken EO: Effect of monoclonal antibodies to enteroglucagon on ileal adaptation after proximal small bowel resection. Gut 28:9–14, 1987

    Google Scholar 

  53. Munroe DG, Gupta AK, Kooshesh F, Vyas TB, Rizkalla G, Wong H, Demchyshyn L, Yang Z, Kamboj RK, Cheng H, McCallum K, Summer-Smith M, Drucker DJ, Crivici A: Prototypic G protein-coupled receptor for the intestinotrophic factor glucagon-like peptide 2. Proc Natl Acad Sci USA 96:1569–1573, 1999

    Google Scholar 

  54. Allard JP, Jeejeebhoy KN: Nutrional support and therapy in the short bowel syndrome. Gastroenterol. Clin North Am 18:589–601, 1989

    Google Scholar 

  55. Cosnes J, Gendre JP, Le Quintrec Y: Role of the ileocecal valve and site of intestinal resection in malabsorption after extensive small bowel resection. Digestion 18:329–336, 1978

    Google Scholar 

  56. Thompson JS, Quigley EM, Adrian TE: Factors affecting outcome following proximal and distal intestinal resection in the dog. Dig Dis Sci 44:63–74, 1999

    Google Scholar 

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Authors and Affiliations

  1. Departments of Medical Anatomy and Physiology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark

    Jesper Thulesen, Bolette Hartmann, Hannelouise Kissow, Palle Bekker Jeppesen, Cathrine Ørskov, Jens Juul Holst & Steen Seier Poulsen

  2. Department of Medicine CA-2121, Section of Gastroenterology, National University Hospital, University of Copenhagen, Copenhagen, Denmark

    Jesper Thulesen, Bolette Hartmann, Hannelouise Kissow, Palle Bekker Jeppesen, Cathrine Ørskov, Jens Juul Holst & Steen Seier Poulsen

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  1. Jesper Thulesen
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Thulesen, J., Hartmann, B., Kissow, H. et al. Intestinal Growth Adaptation and Glucagon-like Peptide 2 in Rats with Ileal–Jejunal Transposition or Small Bowel Resection. Dig Dis Sci 46, 379–388 (2001). https://doi.org/10.1023/A:1005572832571

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