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No effect of physiological concentrations of glucagon-like peptide-2 on appetite and energy intake in normal weight subjects

International Journal of Obesity volume 27, pages 450–456 (2003)Cite this article

Abstract

OBJECTIVE: To examine the effect of a GLP-2 infusion on appetite sensations and ad libitum energy intake in healthy, normal weight humans.

DESIGN: The experiment was performed in a randomised, blinded, and placebo-controlled crossover design. Placebo or GLP-2 was infused (infusion rate of 25 pmol/kg body wth) for 4.5 h.

SUBJECTS: A total of 18 healthy, normal weight young subjects participated; eight women and 10 men.

MEASUREMENTS: During the infusion, subjects recorded their appetite sensations every 30 min using visual analogue scales, and blood was sampled frequently. After 2 h of infusion, an ad libitum meal, consisting of sandwiches, was served.

RESULTS: The concentration of GLP-2 was significantly higher during the GLP-2 infusion compared with placebo (P<0.0001) and increased further in both conditions in response to the meal. Neither appetite sensations, nor palatability of the test meals, or energy intake were different on the two occasions. Glucose, GLP-1, insulin, and GIP responses were also unaffected by the infusion, whereas glucagon levels were higher during the GLP-2 treatment (P<0.05).

CONCLUSION: Circulating GLP-2 in physiological concentrations does not seem to play a significant role in human appetite regulation.

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References

  1. Bell GI, Santerre RF, Mullenbach GT . Hamster preproglucagon contains the sequence of glucagon and two related peptides. Nature 1983; 302: 716–718.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  3. Drucker DJ, Ehrlich P, Asa SL, Brubaker PL . Induction of intestinal epithelial proliferation by glucagon-like peptide 2. Proc Natl Acad Sci USA 1996; 93: 7911–7916.

    Article  CAS  Google Scholar 

  4. Tsai C, Hill M, Drucker DJ . Biological determinants of intestinotrophic properties of GLP-2 in vivo. Am J Physiol 1997; 272: G662–G668.

    CAS  PubMed  Google Scholar 

  5. Tsai C, Hill M, Asa SL, Brubaker PL, Drucker DJ . Intestinal growth-promoting properties of glucagon-like peptide-2 in mice. Am J Physiol 1997; 273: E77–E84.

    Article  CAS  Google Scholar 

  6. Cheeseman CI, Tsang R . The effect of gastric inhibitory polypeptide and glucagon-like peptides on intestinal hexose transport. Am J Physiol 1996; 271: G477–G482.

    CAS  PubMed  Google Scholar 

  7. Cheeseman CI . Upregulation of SGLT-1 transport activity in rat jejunum induced by GLP-2 infusion in vivo. Am J Physiol 1997; 273: R1965–R1971.

    CAS  PubMed  Google Scholar 

  8. Flint A, Raben A, Astrup A, Holst JJ . Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest 1998; 101: 515–520.

    Article  CAS  Google Scholar 

  9. Gutzwiller JP, Göke B, Drewe J, Hildebrand P, Ketterer S, Handschin D, Winterhalder R, Conen D, Beglinger C . Glucagon-like peptide-1: a potent regulator of food intake in humans. Gut 1999; 44: 81–86.

    Article  CAS  Google Scholar 

  10. Näslund E, Barkeling B, King N, Gutniak M, Blundell JE, Holst JJ, Rösner S, Hellström PM . Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men. Int J Obes Relat Metab Disord 1999; 23: 304–311.

    Article  Google Scholar 

  11. Ø rskov C, Holst JJ, Knuhtsen S, Baldissera FGA, Poulsen SS, Nielsen OV . Glucagon-like peptides GLP-1 and GLP-2, predicted products of the glucagon gene, are secreted separately from pig small intestine but not from pancreas. Endocrinology 1986; 119: 1467–1473.

    Article  Google Scholar 

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

    Article  Google Scholar 

  13. Xiao Q, Boushey RP, Drucker DJ, Brubaker PL . Secretion of intestinotropic hormone glucagon-like peptide 2 is differentially regulated by nutrients in humans. Gastroentology 1999; 117: 99–105.

    Article  CAS  Google Scholar 

  14. Hartmann B, Johnsen AH, ørskov C, Adelhorst K, Thim L, Holst JJ . Structure, measurement, and secretion of human glucagon-like peptide-2. Peptides 2000; 21: 73–80.

    Article  CAS  Google Scholar 

  15. Tang-Christensen M, Larsen PJ, Thulesen J, Rømer J, Vrang N . The proglucagon-derived peptide, glucagon-like peptide-2, is a neurotransmitter involved in the regulation of food intake. Nat Med 2000; 6: 802–807.

    Article  CAS  Google Scholar 

  16. Munroe DG, Gupta AK, Kooshesh F, Vyas TB, Rizkalla G, Wang H, Demchysyn L, Yang Z, Kamboj RK, Chen H, McCallum K, Sumner-Smith M, Drucker DJ, Crivici A . Prototypic G protein-coupled receptor for the intestinotropic factor glucagon-like peptide 2. Proc Natl Acad Sci USA 1999; 96: 1569–1573.

    Article  CAS  Google Scholar 

  17. Wøjdemann M, Wettergren A, Hartmann B, Holst JJ . Glucagon-like peptide-2 inhibits centrally induced antral motility in pigs. Scand J Gastroenterol 1998; 33: 828–832.

    PubMed  Google Scholar 

  18. Wøjdemann M, Wettergren A, Hartmann B, Hilstad L, Holst JJ . Inhibition of sham feeding-stimulated human gastric secretion by glucagon-like peptide-2. J Clin Endocrinol Metab 1999; 84: 2513–2517.

    Article  Google Scholar 

  19. Klausen B, Toubro S, Astrup A . Age and sex effects on energy expenditure. Am J Clin Nutr 1997; 65: 895–907.

    Article  CAS  Google Scholar 

  20. FAO. Energy and protein requirements. Report of a Joint FAO/UNI Expert Consultation. World Health Organization: Geneva; 1985.

  21. Costill DL . Carbohydrates for exercise: dietary demands for optimal performance. Int J Sports Med 1988; 9: 1–18.

    Article  CAS  Google Scholar 

  22. Heitmann BL . Prediction of body water and fat in adult danes from measurement of electrical impedance. A validation study. Int J Obes Relat Metab Disord 1990; 14: 789–802.

    CAS  Google Scholar 

  23. Raben A, Tagliabue A, Astrup A . The reproducibility of subjective appetite scores. Br J Nutr 1995; 73: 517–530.

    Article  CAS  Google Scholar 

  24. Hartmann B, Harr MB, Jeppesen PB, Wøjdemann M, Deacon CF, Mortensen PB, Holst JJ . In vivo and in vitro degradation of glucagon-like peptide-2 in humans. J Clin Endocrinol Metab 2000; 85: 2884–2888.

    CAS  PubMed  Google Scholar 

  25. Bergmayer HV (ed). Methods of enzymatic analysis. Academic Press, Inc.: New York; 1974.

    Google Scholar 

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

    Article  CAS  Google Scholar 

  27. 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 1994; 43: 535–537.

    Article  Google Scholar 

  28. Krarup T, Madsbad S, Moody AJ, Regeur L, Faber OK, Holst JJ, Sestoft L . Diminished gastric inhibitory polypeptide (GIP) response to a meal in newly diagnosed type I (insulin dependent) diabetics. J Clin Endocrinol Metab 1983; 56: 1306–1312.

    Article  CAS  Google Scholar 

  29. Holst JJ . Evidence that enteroglucagon (II) is identical with the C-terminal sequence (residues 33–39) of glicentin. Biochem J 1982; 207: 381–388.

    Article  CAS  Google Scholar 

  30. Jeppesen PB, Hartmann B, Thulesen J, Graff J, Lohman J, Hansen BS, Tofteng F, Poulsen SS, Madsen JL, Holst JJ, Mortensen PB . Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short bowel patients with no colon. Gastroenterology 2000; 120: 806–815.

    Article  Google Scholar 

  31. Näslund E, Bogefors J, Skogar S, Grybäck, Jacobsson H, Holst JJ, Hellström PM . GLP-1 slows solid gastric emptying and inhibits insulin, glucagon, and PYY release in humans. Am J Physiol 1999; 277: R910–R916.

    PubMed  Google Scholar 

  32. Layer P, Holst JJ, Grandt D, Goebell H . Ileal release of glucagon-like peptide-1 (GLP-1). Association with inhibition of gastric acid secretion in humans. Dig Dis Sci 1995; 40: 1074–1082.

    Article  CAS  Google Scholar 

  33. Wettergren A, Schjoldager B, Mortensen PE, Myhre J, Christiansen J, Holst JJ . Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man. Dig Dis Sci 1993; 38: 665–673.

    Article  CAS  Google Scholar 

  34. Larsen PJ, Tang-Christensen M, Holst JJ, Ørskov C . Distribution of glucagon-like peptide-1 and other preproglucagon-derived peptides in the rat hypothalamus and brainstem. Neuroscience 1997; 77: 257–270.

    Article  CAS  Google Scholar 

  35. Flint A, Raben A, Blundell JE, Astrup A . Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. Int J Obes Relat Metab Disord 1999; 24: 38–48.

    Article  Google Scholar 

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Acknowledgements

We thank Lene Alboek, Inge Timmermann, Christina Hansen, Yvonne Rasmussen, and Charlotte Kostecki for expert assistance. We gratefully acknowledge the participation of all the persons involved in the study.

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Authors and Affiliations

  1. Department of Human Nutrition, Centre for Advanced Food Studies, The Royal Veterinary and Agricultural University, Frederiksberg C, DK-1958, Denmark

    L B Sørensen, A Flint, A Raben & A Astrup

  2. Department of Medical Physiology, The Panum Institute, University of Copenhagen, Copenhagen N, DK-2200, Denmark

    B Hartmann & J J Holst

Authors
  1. L B Sørensen
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  2. A Flint
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  3. A Raben
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  4. B Hartmann
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  5. J J Holst
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  6. A Astrup
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Correspondence to L B Sørensen.

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Novo Nordisk and The Danish Medical Research Council supported this study.

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Sørensen, L., Flint, A., Raben, A. et al. No effect of physiological concentrations of glucagon-like peptide-2 on appetite and energy intake in normal weight subjects. Int J Obes 27, 450–456 (2003). https://doi.org/10.1038/sj.ijo.0802247

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