Skip to main content
Gut logoLink to Gut
. 1987;28(Suppl):9–14. doi: 10.1136/gut.28.suppl.9

Effect of monoclonal antibodies to enteroglucagon on ileal adaptation after proximal small bowel resection.

M Gregor 1, H Menge 1, R Stössel 1, E O Riecken 1
PMCID: PMC1434568  PMID: 3692320

Abstract

On the basis of circumstantial clinical and experimental evidence, it has been suggested that enteroglucagon (EG) may act as an enterotrophic factor. This study was undertaken to evaluate the effects of long term in vivo immunoneutralisation of EG, using monoclonal antibodies to EG, on the hyperplastic ileal response after small bowel resection. Nineteen rats had a 70% proximal resection. A group of 10 rats was given iv 0.5 ml of undiluted hybridoma ascites immediately after the operation and on the 7th day postoperatively. Furthermore 0.025 ml/day of the same hybridoma ascitic fluid was continuously delivered ip for 14 days via mini-osmotic pumps. The hybridoma ascites was prepared from the clone 23.6B4 synthesising a monoclonal antibody directed toward the N-terminal to central region of the glucagon molecule which showed a marked crossreaction with EG. A control group of 9 rats was given a corresponding amount of antibody-free plasmacytoma ascites (Ag 8.653) by the same technique. Seven and 14 days postoperatively there was a plasma anti-EG-antibody excess with an excess binding capacity of 84.9 glucagon eq nM and 88.5 glucagon eq nM respectively. The three dimensional architecture and the proliferative activity of the ileal remnant were evaluated two weeks postoperatively. Despite a continuous immunoneutralisation of circulating endogenous EG by monoclonal antibodies, the adaptive response of the ileal remnants was of the same magnitude as that seen in the control group. These data do not support the hypothesis that EG is a circulating enterotrophic regulatory peptide.

Full text

PDF
11

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bell G. I., Sanchez-Pescador R., Laybourn P. J., Najarian R. C. Exon duplication and divergence in the human preproglucagon gene. 1983 Jul 28-Aug 3Nature. 304(5924):368–371. doi: 10.1038/304368a0. [DOI] [PubMed] [Google Scholar]
  2. Bell G. I., Santerre R. F., Mullenbach G. T. Hamster preproglucagon contains the sequence of glucagon and two related peptides. Nature. 1983 Apr 21;302(5910):716–718. doi: 10.1038/302716a0. [DOI] [PubMed] [Google Scholar]
  3. Bloom S. R. An enteroglucagon tumour. Gut. 1972 Jul;13(7):520–523. doi: 10.1136/gut.13.7.520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chey W. Y., Kim M. S., Lee K. Y., Chang T. M. Effect of rabbit antisecretin serum on postprandial pancreatic secretion in dogs. Gastroenterology. 1979 Dec;77(6):1268–1275. [PubMed] [Google Scholar]
  5. Christofides N. D., Bryant M. G., Ghatei M. A., Kishimoto S., Buchan A. M., Polak J. M., Bloom S. R. Molecular forms of motilin in the mammalian and human gut and human plasma. Gastroenterology. 1981 Feb;80(2):292–300. [PubMed] [Google Scholar]
  6. Clarke R. M. Mucosal architecture and epithelial cell production rate in the small intestine of the albino rat. J Anat. 1970 Nov;107(Pt 3):519–529. [PMC free article] [PubMed] [Google Scholar]
  7. Ebert R., Creutzfeldt W. Influence of gastric inhibitory polypeptide antiserum on glucose-induced insulin secretion in rats. Endocrinology. 1982 Nov;111(5):1601–1606. doi: 10.1210/endo-111-5-1601. [DOI] [PubMed] [Google Scholar]
  8. Ebert R., Illmer K., Creutzfeldt W. Release of gastric inhibitory polypeptide (GIP) by intraduodenal acidification in rats and humans and abolishment of the incretin effect of acid by GIP-antiserum in rats. Gastroenterology. 1979 Mar;76(3):515–523. [PubMed] [Google Scholar]
  9. Ebert R., Unger H., Creutzfeldt W. Preservation of incretin activity after removal of gastric inhibitory polypeptide (GIP) from rat gut extracts by immunoadsorption. Diabetologia. 1983 Jun;24(6):449–454. doi: 10.1007/BF00257346. [DOI] [PubMed] [Google Scholar]
  10. Frohman L. A., Reichlin M., Sokal J. E. Immunologic and biologic properties of antibodies to a glucagon-serum albumin polymer. Endocrinology. 1970 Nov;87(5):1055–1061. doi: 10.1210/endo-87-5-1055. [DOI] [PubMed] [Google Scholar]
  11. GREGOR W. H., MARTIN J. M., WILLIAMSON J. R., LACY P. E., KIPNIS D. M. A study of the diabetic syndrome produced in rats by anti-insulin serum. Diabetes. 1963 Jan-Feb;12:73–81. doi: 10.2337/diab.12.1.73. [DOI] [PubMed] [Google Scholar]
  12. Gleeson M. H., Bloom S. R., Polak J. M., Henry K., Dowling R. H. Endocrine tumour in kidney affecting small bowel structure, motility, and absorptive function. Gut. 1971 Oct;12(10):773–782. doi: 10.1136/gut.12.10.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goyal R. K., McGuigan J. E. Is gastrin a major determinant of basal lower esophageal sphincter pressure? A double-blind controlled study using high titer gastrin antiserum. J Clin Invest. 1976 Feb;57(2):291–300. doi: 10.1172/JCI108280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gregor M., Riecken E. O. Production and characterization of N-terminally and C-terminally directed monoclonal antibodies against pancreatic glucagon. Gastroenterology. 1985 Sep;89(3):571–580. doi: 10.1016/0016-5085(85)90453-6. [DOI] [PubMed] [Google Scholar]
  15. Górnacz G. E., Al-Mukhtar M. Y., Ghatei M. A., Sagor G. R., Wright N. A., Bloom S. R. Pattern of cell proliferation and enteroglucagon response following small bowel resection in the rat. Digestion. 1984;29(2):65–72. doi: 10.1159/000199012. [DOI] [PubMed] [Google Scholar]
  16. Hanson W. R., Osborne J. W., Sharp J. G. Compensation by the residual intestine after intestinal resection in the rat. I. Influence of amount of tissue removed. Gastroenterology. 1977 Apr;72(4 Pt 1):692–700. [PubMed] [Google Scholar]
  17. Hanson W. R., Osborne J. W., Sharp J. G. Compensation by the residual intestine after intestinal resection in the rat. II. Influence of postoperative time interval. Gastroenterology. 1977 Apr;72(4 Pt 1):701–705. [PubMed] [Google Scholar]
  18. Holst J. J., Galbo H., Richter E. A. Neutralization of glucagon by antiserum as a tool in glucagon physiology. Lack of depression of basal blood glucose after antiserum treatment in rats. J Clin Invest. 1978 Jul;62(1):182–190. doi: 10.1172/JCI109104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lauritsen B., Holst J. J., Moody A. J. Depression of insulin release by anti-GIP serum after oral glucose in rats. Scand J Gastroenterol. 1981 Apr;16(3):417–420. doi: 10.3109/00365528109181990. [DOI] [PubMed] [Google Scholar]
  20. Lorenz-Meyer H., Köhn R., Riecken E. O. Vergleich verschiedener morphometrischer Methoden zur Erfassung der Schleimhautoberfläche des Rattendünndarms und deren Beziehung zur Funktion. Histochemistry. 1976 Oct 22;49(2):123–129. doi: 10.1007/BF00495676. [DOI] [PubMed] [Google Scholar]
  21. Maruyama H., Tominaga M., Bolli G., Orci L., Unger R. H. The alpha cell response to glucose change during perfusion of anti-insulin serum in pancreas isolated from normal rats. Diabetologia. 1985 Nov;28(11):836–840. doi: 10.1007/BF00291074. [DOI] [PubMed] [Google Scholar]
  22. Menge H., Hopert R., Alexopoulos T., Riecken E. O. Three-dimensional structure and cell kinetics at different sites of rat intestinal remnants during the early adaptive response to resection. Res Exp Med (Berl) 1982;181(2):77–94. doi: 10.1007/BF01852185. [DOI] [PubMed] [Google Scholar]
  23. Menge H., Robinson J. W. The relationship between the functional and structural alterations in the rat small intestine following proximal resection of varying extents. Res Exp Med (Berl) 1978 Jul 24;173(1):41–53. doi: 10.1007/BF01851373. [DOI] [PubMed] [Google Scholar]
  24. Rodbell M., Krans H. M., Pohl S. L., Birnbaumer L. The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. 3. Binding of glucagon: method of assay and specificity. J Biol Chem. 1971 Mar 25;246(6):1861–1871. [PubMed] [Google Scholar]
  25. Short G. M., Doyle J. W., Wolfe M. M. Effect of antibodies to somatostatin on acid secretion and gastrin release by the isolated perfused rat stomach. Gastroenterology. 1985 Apr;88(4):984–988. doi: 10.1016/s0016-5085(85)80018-4. [DOI] [PubMed] [Google Scholar]
  26. Tan K., Tsiolakis D., Marks V. Effect of glucagon antibodies on plasma glucose, insulin and somatostatin in the fasting and fed rat. Diabetologia. 1985 Jul;28(7):435–440. doi: 10.1007/BF00280887. [DOI] [PubMed] [Google Scholar]
  27. Villar H. V., Watayou T., Booth R. A., Rayford P. L., Reeder D. D., Thompson J. C. Suppression of gastric secretion and serum gastrin by gastrin antibody. Am J Surg. 1976 Jan;131(1):64–68. doi: 10.1016/0002-9610(76)90422-0. [DOI] [PubMed] [Google Scholar]
  28. Wolfe M. M., Hocking M. P., Maico D. G., McGuigan J. E. Effects of antibodies to gastric inhibitory peptide on gastric acid secretion and gastrin release in the dog. Gastroenterology. 1983 May;84(5 Pt 1):941–948. [PubMed] [Google Scholar]
  29. Wright L. J., Feinstein A., Heap R. B., Saunders J. C., Bennett R. C., Wang M. Y. Progesterone monoclonal antibody blocks pregnancy in mice. Nature. 1982 Feb 4;295(5848):415–417. doi: 10.1038/295415a0. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES