Skip to main content
Log in

Glucagon-like Peptide-1 Retards Gastric Emptying and Small Bowel Transit in the Rat (Effect Mediated Through Central or Enteric Nervous Mechanisms)

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

This study investigated effects of glucagon-likepeptide-1(7-36)amide (GLP-1) on gastric emptying, smallintestinal transit, and contractility of smooth musclestrips in rats. GLP-1 at doses of 10 and 20 pmol/kg/min administered intravenouslydose-dependently retarded transit of the small intestine(P < 0.001), while only the higher dose of 20pmol/kg/min retarded gastric emptying (P < 0.01).GLP-1 at concentrations up to 10-4 M didnot affect the basal tone or contractility of thegastrointestinal muscle strips that were stimulated withelectric field stimulation or acetylcholine. Our resultsdemonstrate that small intestinal transit seems moresensitive than gastric emptying to inhibition by GLP-1at physiologic levels in plasma. Furthermore, thisinhibition appears to be mediated through centralmechanisms rather than through peripheral actions. Thus,GLP-1 is suggested to inhibit gastric emptying and smallintestinal transit through an indirect effect viacentral or enteric nervous mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Mojsov S, Heinrich G, Wilson IB, Ravazzola M, Orci L, Habener JF: Preproglucagon gene expression in pancreas and intestine diversifies at the level of posttranslational processing. J Biol Chem 261:11880 - 11886, 1986

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  3. Ørskov C, Holst JJ, Poulsen SS, Kirkegaard P: Pancre atic and intestinal processing of proglucagon in man. Diabe tologia 30:874 - 881, 1987

    Google Scholar 

  4. Holst JJ, Ørskov C, Nielsen OV, Schwartz TW: Truncated glucagon-like peptide I, an insulin-releasing hormone from the distal gut. FEBS Lett 211:169 - 174, 1987

    PubMed  Google Scholar 

  5. Holst JJ: Enteroglucagon. Adv Metab Dis 11:392 - 419, 1988

    Google Scholar 

  6. Kreymann B, Ghatei MA, Williams G, Bloom SR: Glucagonlike peptide-1 7-36: A physiological incretin in man. Lancet 2:1300 - 1303, 1987

    PubMed  Google Scholar 

  7. Mojsov S, Weir GC, Habene r JF: Insulinotropin: Glucagonlike peptide-I (7-37) co-encoded in the glucagon gene is a potent stimulator of insulin rele ase in the perfused rat pancreas. J Clin Invest 79:616 - 619, 1987

    PubMed  Google Scholar 

  8. Ø rskov C, Holst JJ, Nielsen OV: Effect of truncated glucagonlikepeptide-1 (proglucagon-(78 - 107) amide ) on endocrine secretion from pig pancreas, antrum, and non-antral stomach. Endocrinology 123:2009–2013, 1988

    PubMed  Google Scholar 

  9. Wettergre n A, Schjoldager B, Mortensen PE, Myhre J, Christiansen J, Holst JJ: Truncated GLP-1 (proglucagon 78 - 107-mide) inhibits gastric and pancreatic functions in man. Dig Dis Sci 38:665± 673, 1993

    Google Scholar 

  10. Gutniak MK, Juntti-Berggre n L, Hellströ m PM, Guenifi A, Holst JJ, Efendic S: Glucagon-like peptide I enhances the insulinotropic effect of glibenclamide in NIDDM patients and in the perfused rat pancreas. Diabetes Care 19:857 - 863, 1996

    PubMed  Google Scholar 

  11. Ø rskov C, Rabenhøj L, Wettergren A, Kofod H, Holst JJ: Tissue and plasma concentrations of amidated and glycine extended glucagon-like peptide-1 in humans. Diabetes 43:535 -539, 1994

    PubMed  Google Scholar 

  12. Deacon CF, Johnsen AH, Holst JJ: Degradation of glucagonlike peptide-1 by human plasma in vitroyields an N-terminally truncated peptide that is a major endogenous me tabolite in vivo. J Clin Endocrinol Metab 80:952 - 957, 1995

    PubMed  Google Scholar 

  13. Hjelm M, de Verdier C: A methodological study of the enzymatic determination of glucose in blood. Scand J Clin Lab Invest 15:415 - 428, 1963

    PubMed  Google Scholar 

  14. Hellström PM, Nylander G, Rosell PM: Effects of neurotensin on the transit of gastrointe stinal contents in the rat. Acta Physiol Scand 115:239 - 243, 1982

    PubMed  Google Scholar 

  15. Miller MS, Galligan JJ, Burks TF: Accurate measurement of intestinal transit in the rat. J Pharmacol Methods 6:211 - 217, 1981

    PubMed  Google Scholar 

  16. Hellstrøm PM, Johansson C: Neuropeptide Y inhibits the migrating myoelectric complex and delays small intestinal transit in man. J Gastrointest Motil 1:35 - 41, 1989

    Google Scholar 

  17. Tolessa T, Gutniak M, Efendic S, Hellstr÷m PM: Inhibition of migrating myoelectric complex by glucagon-like peptide-1, but not glucagon, is partially mediated through nitric oxide and partially direct. Neurogastroenterol Motil 8:194A, 1996

    Google Scholar 

  18. Giralt M, Guo X, Vergara P: Glucagon-like-peptide-1 induces inhibitory actions in the gastrointestinal tract of the rat. Neurogastroenterol Motil 8:173A, 1996

    Google Scholar 

  19. Wheeler MB, Lu M, Dillon JS, Leng XH, Chen C, Boyd AE: Functional expression of the rat glucagon-like peptide-I receptor, evidence for coupling to both adenylyl cyclase and phospholipase C. Endocrinology 133:57 - 62, 1993

    PubMed  Google Scholar 

  20. Wettergre n A, Petersen H, Ørskov C, Christiansen J, Sheikh SP, Holst JJ: Glucagon-like peptide-1 (GLP-1) 7-36 amide and peptide YY from the L-cell in the ileal mucosa are potent inhibitors of vagally induced gastric acid in man. Scand JGastroenterol 29:501 - 505, 1994

    Google Scholar 

  21. Ørskov C, Wettergren A, Poulsen SDS, Holst JJ: Is the effect of glucagon-like peptide-1 on gastric emptying centrally mediated? Diabetologia 38:A39, 1995

    Google Scholar 

  22. Wei Y, Mojsov S: Tissue-specific expression of the human receptor for glucagon-like peptide-I: brain, heart and pancreatic forms have the same deduced amino acid sequences. FEBS Lett 358:219 - 224, 1995

    PubMed  Google Scholar 

  23. Ørskov C, Poulsen SS, Møller M, Holst JJ: Glucagon-like peptide-1 receptors in the subfornical organ and the area postrema are acce ssible to circulating glucagon-like peptide-1. Diabetes 45:832 - 835, 1996

    PubMed  Google Scholar 

  24. d'Alessio DA, Fujimoto WY, Ensinck JW: Effects of glucagonlike peptide I-(7-36) on re lease of insulin, glucagon, and somatostatin by rat pancreatic islet cell monolayer cultures. Diabetes 38:1534 - 1538, 1989

    PubMed  Google Scholar 

  25. Ishii M, Nakamura T, Kasai F, Onuma T, Baba T, Takebe K: Altered postprandial insulin requirement in IDDM patients with gastroparesis. Diabetes Care 17:901 - 903, 1994

    PubMed  Google Scholar 

  26. Krarup T, Schwartz TW, Hilsted J, Madsbad S, Overlaege O, Sestoft L: Impaired response of pancreatic polypeptide to hypoglycaemia: an early sign of autonomic neuropathy in diabetics. Br Med J 2:1544 - 1546, 1979

    PubMed  Google Scholar 

  27. Cryer PE: Hypoglycaemia-associated autonomic failure. InHypoglycaemia and Diabetes. BM Frier, M Fisher (eds). London, Arnold, 1993, pp 275 - 283

    Google Scholar 

  28. Horowitz M, Dent J: Disordered gastric emptying: me chanical basis, assessment and treatment. Bailliere's Clin Gastroente rol 5:371 - 407, 1991

    Google Scholar 

  29. Kreymann B, Ghatei MA, Schusdziarra V, Bloom SR, Classen M: Does the incretin effect exist for GIP or GLP-1 7-36 amide at physiological glucose concentrations in man? Digestion 46( suppl 1):59, 1990

    PubMed  Google Scholar 

  30. Brown JC, Dryburgh JR, Ross SA, Dupré J: Identification and actions of gastric inhibitory polypeptide. Recent Prog Horm Res 31:487 - 532, 1975

    PubMed  Google Scholar 

  31. Schang JC, Kelly KA: Inhibition of canine interdigestive proximal gastric motility by cholecystokinin octapeptide. Am J Physiol 240:G217 - G220, 1981

    PubMed  Google Scholar 

  32. Szecowka J, Lins PE, Efendic S: Effects of cholecystokinin, gastric inhibitory polypeptide, and secre tin on insulin and glucagon secretion in rats. Endocrinology 110:1268 - 1272, 1982

    PubMed  Google Scholar 

  33. Rushakoff RJ, Goldfine ID, Carter JD, Liddle RA: Physiological concentrations of cholecystokinin stimulate amino acid release in humans. J Clin Endocrinol Metab 65:395 - 401, 1987

    PubMed  Google Scholar 

  34. Bueno L, Ruckebusch Y: Insulin and jejunal electrical activity in dogs and sheep. Am J Physiol 230:G1538 - G1544, 1977

    Google Scholar 

  35. Shima K, Hirota M, Ohboshi C: Effect of glucagon-like peptide-1 on insulin secretion. Regul Pept 22:245 - 252, 1988

    Article  PubMed  Google Scholar 

  36. Komatsu R, Matsuyama T, Namba M, Watanabe N, Itoh H, Kono N, Tarui S: Glucagonostatic and insulinotropic action of glucagonlike peptide I-(7-36)-amide. Diabetes 38:902-905, 1989

    PubMed  Google Scholar 

  37. Gefe l D, Hendrick GK, Mojsov S, Habener JF, Weir GC: Glucagon-like peptide-I analogs: effects on insulin secretion and adenosine 39, 59-monophosphate formation. Endocrinology 126:2164 - 2168, 1990

    PubMed  Google Scholar 

Download references

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tolessa, T., Gutniak, M., Holst, J.J. et al. Glucagon-like Peptide-1 Retards Gastric Emptying and Small Bowel Transit in the Rat (Effect Mediated Through Central or Enteric Nervous Mechanisms). Dig Dis Sci 43, 2284–2290 (1998). https://doi.org/10.1023/A:1026678925120

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026678925120

Navigation