Abstract
After jejunectomy, a rapid and sustained increase in the abundance of proglucagon mRNA occurs in residual ileum and is accompanied by increases in plasma intestinal proglucagon-derived peptides. This response may be a component of adaptive growth, or proglucagon-derived peptides may regulate adaptive growth. To distinguish these possibilities, rats were treated with difluoromethylornithine, blocking ornithine decarboxylase activity and thereby adaptive bowel growth. Three groups fedad libitum were compared: (1) resect: rats with 80% proximal small bowel resection; (2) resect + difluoromethylornithine: resected rats given difluoromethylornithine in drinking water; and (3) transect: transected controls. Six days after surgery, the resect + difluoromethylornithine group demonstrated inhibition of adaptive bowel growth. Abundance of ileal proglucagon mRNA in resect and resect + difluoromethylornithine groups was double that in the transect group (P<0.02), whereas ornithine decarboxylase mRNA levels did not differ. Plasma enteroglucagon and glucagon-like peptide-I levels were greater in resect than transect groups (P<0.002) and did not differ between resect and resect + difluoromethylornithine groups. The rise in ileal proglucagon mRNA after proximal small bowel resection is not inhibited by difluoromethylornithine despite blocking bowel growth and, therefore, is not merely a component of adaptive growth. Proglucagon-derived peptides are possible modulators of adaptive bowel growth but cannot stimulate growth when ornithine decarboxylase activity is inhibited.
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References
Holst JJ: Gut glucagon, enteroglucagon, gut glucagonlike peptides, glicentin: Current status. Gastroenterology 84:1602–1609, 1983
Sagor GR, Ghatei MA, Al-Mukhtar MY, Wright NA, Bloom SR: Evidence for a humoral mechanism after small intestinal resection: Exclusion of gastrin but not enteroglucagon. Gastroenterology 84:902–906, 1983
Bloom SR: An enteroglucagon tumour in man. Gut 13:520–523, 1972
Gregor M, Menge H, Stossel R, Riecken EO: Effect of monoclonal antibodies to enteroglucagon on ileal adaptation after proximal small bowel resection. Gut 28(S1):9–14, 1987
Gregor M, Stallmach A, Menge H, Riecken EO: The role of gut-glucagon-like immunoreactants in the control of gastrointestinal epithelial cell renewal. Digestion 46(suppl 2):59–65. 1990
Goodlad RA, Ghatei MA, Bloom SR, Wright NA: Glucagon 1–21 reduces intestinal epithelial cell proliferation in parenterally fed rats. Exp Physiol 76:943–949, 1991
Mojsov S, Heinrich G, Wilson IB, Ravazzola M, Orci L, Habener JF: Preproglucagon gene expression diversifies at the level of post-translational processing. J Biol Chem 262:11880–11889, 1986
Orsov C, Holst JJ, Knuhtsen S, Baldissera FGA, Poulson SS, Nielson 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
Watanabe N, Matsuyama T, Namba M, Miyagawa J, Itoh H, Komatsu R, Kono N, Tarui S: Trophic effect of glucagon-(1–21)-peptide on the isolated rat ileal mucosal cells. Biochem Biophys Res Commun 152:1038–1044, 1988
Rountree DB, Ulshen MH, Selub S, Fuller CR, Bloom SR, Ghatel MA, Lund PK: Nutrient-independent increases in proglucagon and ornithine decarboxylase messenger RNAs after jejunoileal resection. Gastroenterology 103:462–468, 1992
Taylor RG, Verity K, Fuller PJ: Ileal glucagon gene expression: ontogeny and response to massive small bowel resection. Gastroenterology 99:724–729, 1990
Pegg AE, McCann PE: Polyamine metabolism and function. Am J Physiol 243:C212-C221, 1982
Luk GD, Baylin SB: Polyamines and intestinal growth: increased polyamine biosynthesis after jejunectomy. Am J Physiol 245:G656-G660, 1983
Luk GD, Baylin SB: Inhibition of intestinal epithelial DNA synthesis and adaptive hyperplasia after jejunectomy in the rat by suppression of polyamine biosynthesis. J Clin Invest 74:698–704, 1984
Hanson WR, Osborne JW, Sharp JG: Compensation by the residual intestine after intestinal resection in the rat: II. Influence of postoperative time interval. Gastroenterology 72:701–705, 1977
Ulshen MH, Dowling RH, Fuller CR, Zimmermann EM, Lund PK: Enhanced growth of small bowel in transgenic mice overexpressing bovine growth hormone. Gastroenterology 104:973–980, 1993
Lund PK, Moats-Staats BM, Hynes MA, Simmons JG, Jansen M, D'ercole AJ, Van Wyk JJ: Somatomedin-C/insulin-like growth factor I and insulin-like growth factor II mRNAs in rat fetal and adult tissues. J Biol Chem 261:14539–14544, 1986
van Kranen HJ, van de Zande L, van Kreijl CF, Bisschop A, Weiringa B. Cloning and nucleotide sequence of rat ornithine decarboxylase cDNA. Gene 60:145–155, 1987
Hoyt EC, Van Wyk JJ, Lund PK: Tissue and development specific regulation of a complex family of rat insulin-like growth factor I messenger ribonucleic acids. Mol Endocrinol 2:1077–1086, 1988
Jin, S-LC, Hynes MA, Lund PK: Ontogeny of glucagon messenger RNA and encoded precursor in the rat intestine. Regul Pept 29:117–131, 1990
Bloom SR: Hormones of the gastrointestinal tract. Br Med Bull 30:62–67, 1974
George SK, Uttenthal LO, Ghiglione M, Bloom SR: Molecular forms of glucagon-like peptides in man. FEBS Lett 92:275–278. 1985
Bamba T, Vaja S, Murphy GM, Dowling RH: Role of polyamines in the early adaptive response to jejunectomy in the rat: effect of DFMO on the ileal villus: crypt axis. Digestion 46(suppl 2):410–423, 1990
Taylor RG, Beveridge DJ, Fuller PJ: Expression of ileal glucagon and peptide tyrosine-tyrosine genes. Response to inhibition of polyamine synthesis in the presence of massive smallbowel resection. Biochem J 286:737–741, 1992
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This work was supported by NIH grant DK40247 with assistance from the Center for Gastrointestinal Biology and Disease molecular biology core (NIH grant DK34987).
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Ulshen, M.H., Hoyt, E.C., Fuller, C.R. et al. Increased ileal proglucagon expression after jejunectomy is not suppressed by inhibition of bowel growth. Digest Dis Sci 41, 677–683 (1996). https://doi.org/10.1007/BF02213122
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DOI: https://doi.org/10.1007/BF02213122