Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1998 Feb 1;101(3):515–520. doi: 10.1172/JCI990

Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans.

A Flint 1, A Raben 1, A Astrup 1, J J Holst 1
PMCID: PMC508592  PMID: 9449682

Abstract

We examined the effect of intravenously infused glucagon-like peptide 1 (GLP-1) on subjective appetite sensations after an energy-fixed breakfast, and on spontaneous energy intake at an ad libitum lunch. 20 young, healthy, normal-weight men participated in a placebo-controlled, randomized, blinded, crossover study. Infusion (GLP-1, 50 pmol/ kg.h or saline) was started simultaneously with initiation of the test meals. Visual analogue scales were used to assess appetite sensations throughout the experiment and the palatability of the test meals. Blood was sampled throughout the day for analysis of plasma hormone and substrate levels. After the energy-fixed breakfast, GLP-1 infusion enhanced satiety and fullness compared with placebo (treatment effect: P < 0.03). Furthermore, spontaneous energy intake at the ad libitum lunch was reduced by 12% by GLP-1 infusion compared with saline (P = 0.002). Plasma GLP-1, insulin, glucagon, and blood glucose profiles were affected significantly by the treatment (P < 0.002). In conclusion, the results show that GLP-1 enhanced satiety and reduced energy intake and thus may play a physiological regulatory role in controlling appetite and energy intake in humans.

Full Text

The Full Text of this article is available as a PDF (177.9 KB).

Selected References

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

  1. Albano J. D., Ekins R. P., Maritz G., Turner R. C. A sensitive, precise radioimmunoassay of serum insulin relying on charcoal separation of bound and free hormone moieties. Acta Endocrinol (Copenh) 1972 Jul;70(3):487–509. doi: 10.1530/acta.0.0700487. [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. Costill D. L. Carbohydrates for exercise: dietary demands for optimal performance. Int J Sports Med. 1988 Feb;9(1):1–18. doi: 10.1055/s-2007-1024971. [DOI] [PubMed] [Google Scholar]
  4. Deacon C. F., Pridal L., Klarskov L., Olesen M., Holst J. J. Glucagon-like peptide 1 undergoes differential tissue-specific metabolism in the anesthetized pig. Am J Physiol. 1996 Sep;271(3 Pt 1):E458–E464. doi: 10.1152/ajpendo.1996.271.3.E458. [DOI] [PubMed] [Google Scholar]
  5. Drucker D. J., Erlich P., Asa S. L., Brubaker P. L. Induction of intestinal epithelial proliferation by glucagon-like peptide 2. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7911–7916. doi: 10.1073/pnas.93.15.7911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Göke R., Larsen P. J., Mikkelsen J. D., Sheikh S. P. Distribution of GLP-1 binding sites in the rat brain: evidence that exendin-4 is a ligand of brain GLP-1 binding sites. Eur J Neurosci. 1995 Nov 1;7(11):2294–2300. doi: 10.1111/j.1460-9568.1995.tb00650.x. [DOI] [PubMed] [Google Scholar]
  7. Heitmann B. L. Prediction of body water and fat in adult Danes from measurement of electrical impedance. A validation study. Int J Obes. 1990 Sep;14(9):789–802. [PubMed] [Google Scholar]
  8. Holst J. J. Enteroglucagon. Annu Rev Physiol. 1997;59:257–271. doi: 10.1146/annurev.physiol.59.1.257. [DOI] [PubMed] [Google Scholar]
  9. Holst J. J. Evidence that enteroglucagon (II) is identical with the C-terminal sequence (residues 33-69) of glicentin. Biochem J. 1982 Dec 1;207(3):381–388. doi: 10.1042/bj2070381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Holst J. J., Schwartz T. W., Lovgreen N. A., Pedersen O., Beck-Nielsen H. Diurnal profile of pancreatic polypeptide, pancreatic glucagon, gut glucagon and insulin in human morbid obesity. Int J Obes. 1983;7(6):529–538. [PubMed] [Google Scholar]
  11. Hvidberg A., Nielsen M. T., Hilsted J., Orskov C., Holst J. J. Effect of glucagon-like peptide-1 (proglucagon 78-107amide) on hepatic glucose production in healthy man. Metabolism. 1994 Jan;43(1):104–108. doi: 10.1016/0026-0495(94)90164-3. [DOI] [PubMed] [Google Scholar]
  12. Kieffer T. J., McIntosh C. H., Pederson R. A. Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology. 1995 Aug;136(8):3585–3596. doi: 10.1210/endo.136.8.7628397. [DOI] [PubMed] [Google Scholar]
  13. Kolligs F., Fehmann H. C., Göke R., Göke B. Reduction of the incretin effect in rats by the glucagon-like peptide 1 receptor antagonist exendin (9-39) amide. Diabetes. 1995 Jan;44(1):16–19. doi: 10.2337/diab.44.1.16. [DOI] [PubMed] [Google Scholar]
  14. Larsen P. J., Tang-Christensen M., Holst J. J., Orskov C. Distribution of glucagon-like peptide-1 and other preproglucagon-derived peptides in the rat hypothalamus and brainstem. Neuroscience. 1997 Mar;77(1):257–270. doi: 10.1016/s0306-4522(96)00434-4. [DOI] [PubMed] [Google Scholar]
  15. Miholic J., Orskov C., Holst J. J., Kotzerke J., Meyer H. J. Emptying of the gastric substitute, glucagon-like peptide-1 (GLP-1), and reactive hypoglycemia after total gastrectomy. Dig Dis Sci. 1991 Oct;36(10):1361–1370. doi: 10.1007/BF01296800. [DOI] [PubMed] [Google Scholar]
  16. Mojsov S., Heinrich G., Wilson I. B., Ravazzola M., Orci L., Habener J. F. Preproglucagon gene expression in pancreas and intestine diversifies at the level of post-translational processing. J Biol Chem. 1986 Sep 5;261(25):11880–11889. [PubMed] [Google Scholar]
  17. Nakabayashi H., Nishizawa M., Nakagawa A., Takeda R., Niijima A. Vagal hepatopancreatic reflex effect evoked by intraportal appearance of tGLP-1. Am J Physiol. 1996 Nov;271(5 Pt 1):E808–E813. doi: 10.1152/ajpendo.1996.271.5.E808. [DOI] [PubMed] [Google Scholar]
  18. Nauck M. A., Kleine N., Orskov C., Holst J. J., Willms B., Creutzfeldt W. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia. 1993 Aug;36(8):741–744. doi: 10.1007/BF00401145. [DOI] [PubMed] [Google Scholar]
  19. Nauck M. A., Niedereichholz U., Ettler R., Holst J. J., Orskov C., Ritzel R., Schmiegel W. H. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol. 1997 Nov;273(5 Pt 1):E981–E988. doi: 10.1152/ajpendo.1997.273.5.E981. [DOI] [PubMed] [Google Scholar]
  20. Orskov C., Holst J. J., Knuhtsen S., Baldissera F. G., Poulsen S. S., Nielsen O. V. 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. 1986 Oct;119(4):1467–1475. doi: 10.1210/endo-119-4-1467. [DOI] [PubMed] [Google Scholar]
  21. Orskov C., Poulsen S. S., Møller M., Holst J. J. Glucagon-like peptide I receptors in the subfornical organ and the area postrema are accessible to circulating glucagon-like peptide I. Diabetes. 1996 Jun;45(6):832–835. doi: 10.2337/diab.45.6.832. [DOI] [PubMed] [Google Scholar]
  22. Orskov C., Rabenhøj L., Wettergren A., Kofod H., Holst J. J. Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide I in humans. Diabetes. 1994 Apr;43(4):535–539. doi: 10.2337/diab.43.4.535. [DOI] [PubMed] [Google Scholar]
  23. Orskov C., Wettergren A., Holst J. J. Secretion of the incretin hormones glucagon-like peptide-1 and gastric inhibitory polypeptide correlates with insulin secretion in normal man throughout the day. Scand J Gastroenterol. 1996 Jul;31(7):665–670. doi: 10.3109/00365529609009147. [DOI] [PubMed] [Google Scholar]
  24. Raben A., Tagliabue A., Astrup A. The reproducibility of subjective appetite scores. Br J Nutr. 1995 Apr;73(4):517–530. doi: 10.1079/bjn19950056. [DOI] [PubMed] [Google Scholar]
  25. Ranganath L. R., Beety J. M., Morgan L. M., Wright J. W., Howland R., Marks V. Attenuated GLP-1 secretion in obesity: cause or consequence? Gut. 1996 Jun;38(6):916–919. doi: 10.1136/gut.38.6.916. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Read N., French S., Cunningham K. The role of the gut in regulating food intake in man. Nutr Rev. 1994 Jan;52(1):1–10. doi: 10.1111/j.1753-4887.1994.tb01347.x. [DOI] [PubMed] [Google Scholar]
  27. Ritzel R., Orskov C., Holst J. J., Nauck M. A. Pharmacokinetic, insulinotropic, and glucagonostatic properties of GLP-1 [7-36 amide] after subcutaneous injection in healthy volunteers. Dose-response-relationships. Diabetologia. 1995 Jun;38(6):720–725. doi: 10.1007/BF00401846. [DOI] [PubMed] [Google Scholar]
  28. Scrocchi L. A., Brown T. J., MaClusky N., Brubaker P. L., Auerbach A. B., Joyner A. L., Drucker D. J. Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. Nat Med. 1996 Nov;2(11):1254–1258. doi: 10.1038/nm1196-1254. [DOI] [PubMed] [Google Scholar]
  29. Smith G. P., Gibbs J. Satiating effect of cholecystokinin. Ann N Y Acad Sci. 1994 Mar 23;713:236–241. doi: 10.1111/j.1749-6632.1994.tb44071.x. [DOI] [PubMed] [Google Scholar]
  30. Tang-Christensen M., Larsen P. J., Göke R., Fink-Jensen A., Jessop D. S., Møller M., Sheikh S. P. Central administration of GLP-1-(7-36) amide inhibits food and water intake in rats. Am J Physiol. 1996 Oct;271(4 Pt 2):R848–R856. doi: 10.1152/ajpregu.1996.271.4.R848. [DOI] [PubMed] [Google Scholar]
  31. Turton M. D., O'Shea D., Gunn I., Beak S. A., Edwards C. M., Meeran K., Choi S. J., Taylor G. M., Heath M. M., Lambert P. D. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature. 1996 Jan 4;379(6560):69–72. doi: 10.1038/379069a0. [DOI] [PubMed] [Google Scholar]
  32. Wang Z., Wang R. M., Owji A. A., Smith D. M., Ghatei M. A., Bloom S. R. Glucagon-like peptide-1 is a physiological incretin in rat. J Clin Invest. 1995 Jan;95(1):417–421. doi: 10.1172/JCI117671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wettergren A., Maina P., Boesby S., Holst J. J. Glucagon-like peptide-1 7-36 amide and peptide YY have additive inhibitory effect on gastric acid secretion in man. Scand J Gastroenterol. 1997 Jun;32(6):552–555. doi: 10.3109/00365529709025098. [DOI] [PubMed] [Google Scholar]
  34. Wettergren A., Schjoldager B., Mortensen P. E., Myhre J., Christiansen J., Holst J. J. Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man. Dig Dis Sci. 1993 Apr;38(4):665–673. doi: 10.1007/BF01316798. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES