Skip to main content
Log in

GLP-1 (glucagon-like peptide 1) and truncated GLP-1, fragments of human proglucagon, inhibit gastric acid secretion in humans

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

Abstract

Glucagon-like peptide 1 amide (GLP-1 amide), a predicted product of the glucagon gene (proglucagon 72-107-amide), and truncated GLP-1 (proglucagon 78-107-amide), recently isolated from porcine small intestine, were infused in doses of 100 and 400 ng/kg/hr and 12.5 and 50 ng/kg/hr, respectively, into eight volunteers to study pharmacokinetics and effects on pentagastrin- stimulated gastric acid secretion (plateau stimulation with pentagastrin at D 50:100ng/kg/hr). The concentration of GLP-1 in plasma increased from 64±12 to 189±23 and 631±76 pmol/liter, respectively. The concentration of truncated GLP increased from approximately 7 pmol/liter to 28±3 pmol/liter during the high rate of infusion. A similar increase was seen in response to a mixed meal in eight normal volunteers. The metabolic clearance rate (MCR) of GLP-1 was 2.2±0.3 and 2.6±0.3 ml/kg/min, respectively, and the half- life in plasma was 17±2 min. The MCR of truncated GLP-1 was 13±2.8 ml/kg/min and the half- life 11.4±2.1 min. GLP-1 reduced the pentagastrin- stimulated acid secretion 16±9% during the low-rate infusion and 23±12% during the high rate (P<0.05). Truncated GLP-1 caused a 36±3% inhibition during the high infusion rate. Thus truncated GLP-1, a naturally occurring peptide, is a potent inhibitor of acid secretion in man and more so than GLP-1.

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. Bell GI, Sanchez-Pescador R, Laybourn PJ, Najarian RC: Exon duplication and divergence in the human preproglucagon gene. Nature 304:368–371, 1983

    PubMed  Google Scholar 

  2. Novak U, Wilks A, Buell G, McEwen S: Identical mRNA for preproglucagon in pancreas and gut. Eur J Biochem 164:553–558, 1987

    PubMed  Google Scholar 

  3. Holst JJ, Olsen J, Lund T: Are the enteroglucagons encoded by the glucagon gene? Diabetologia 30:532A, 1987

    Google Scholar 

  4. Ørskov C, Holst JJ, Knuhtsen S, Baldissera F, Poulsen SS, Vagn Nielsen O: 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

    PubMed  Google Scholar 

  5. Ørskov C, Holst JJ, Seier Poulsen S, Kierkegaard P: Pancreatic and intestinal processing of proglucagon in man. Diabetologia 30:874–881, 1987

    PubMed  Google Scholar 

  6. Ørskov C, Holst JJ: Radio-immunoassays for glucagon-like peptides 1 and 2 (GLP-1 and GLP-2). Scand J Clin Lab Invest 47:165–174, 1987

    PubMed  Google Scholar 

  7. Bradbury AF, Finnie MDA, Smyth DG: Mechanism of C-terminal amide formation by pituitary enzymes. Nature 298:686–688, 1983

    Google Scholar 

  8. Schmidt WE, Siegel EG, Creutzfeldt W: Glucagon-like peptide-1 but not glucagon-like peptide-2 stimulates insulin release from isolated rat pancreatic islets. Diabetologia 28:704–707, 1985

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  10. Mojsov S, Weir GC, Habener JF: Insulinotropin: Glucagon-like peptide I (7–37) coencoded in the glucagon gene is a potent stimulator of insulin release in the perfused rat pancreas. J Clin Invest 79:616–619, 1987

    PubMed  Google Scholar 

  11. Petersen B, Christiansen J, Kirkegaard P, Skov Olsen P: The stability of gastric acid secretion during prolonged pentagastrin stimulation in man. Clin Sci 66:99–101, 1984

    PubMed  Google Scholar 

  12. Holst JJ: Evidence that enteroglucagon (II) is identical with the C-terminal sequence (residues 33–69) of glicentin. Biochem J 87:372–378, 1982

    Google Scholar 

  13. Albano JDM, Ekins RP, Mantz G, Turner RC: A sensitive precise radioimmunoassay for serum insulin relying on charcoal separation of bound and free hormone moieties. Acta Endocrinol 70:487–509, 1972

    PubMed  Google Scholar 

  14. Widdonson GM, Penton JR: Determination of serum and plasma glucose on the “autoanalyzer II” by use of hexokinase reaction. Clin Chem 18:299–300, 1972

    PubMed  Google Scholar 

  15. Conover WJ: Practical Nonparametric Statistics, 2nd ed. J Wiley & Sons, New York, 1980, p 299

    Google Scholar 

  16. Polonsky KS, Jaspan JB, Rubenstein AH: The metabolic clearance rate of glucagon. Glucagon II. Handb Exp Pharmacol 66 (2):353–360, 1983

    Google Scholar 

  17. Ghiglione M, Uttenthal LO, George SK, Bloom SR: How glugagon-like is glucagon-like-peptide 1? Diabetologia 27:599–600, 1984

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  19. Schjoldager BTG, Baldissera FGA, Mortensen PE, Holst JJ, Christiansen J: Oxyntomodulin, a potential hormone from the distal gut. Pharmacokinetics and effects on gastric acid and insulin secretion in man. Eur J Clin Invest 18:499–503, 1988

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This study was supported by the Danish Medical Research Council, Novo's Fond and Owesen's Fond.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schjoldager, B.T.G., Mortensen, P.E., Christiansen, J. et al. GLP-1 (glucagon-like peptide 1) and truncated GLP-1, fragments of human proglucagon, inhibit gastric acid secretion in humans. Digest Dis Sci 34, 703–708 (1989). https://doi.org/10.1007/BF01540341

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01540341

Key words

Navigation