Skip to main content
Log in

Glucose metabolism during ghrelin infusion in patients with anorexia nervosa

  • Original Articles
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Anorexia nervosa (AN) is an eating disorder characterized by self-induced starvation due to fear of adiposity. Ghrelin, gastric peptide with potent orexigenic, adipogenic, GH-releasing and metabolic properties, is elevated in AN. We have previously shown that intervention with exogenous ghrelin is not effective in terms of inducing neuroendocrine and appetite responses in AN. In this arm of the same study protocol we investigated glucose metabolism responses to 5 h iv infusion of active ghrelin in a) 9 severely malnourished AN patients, b) 6 AN patients who partially recovered body weight (PRAN), c) 10 constitutionally thin female subjects with regular menstrual cycles. At baseline, no significant differences were observed in blood glucose, insulin, c-peptide, adiponectin, and homeostasis model assessment index values, between the studied groups. During ghrelin infusions, blood glucose levels significantly increased in all groups although significantly less in low-weight AN; insulin levels were not significantly affected, while c-peptide levels were significantly suppressed only in the constitutionally thin and PRAN subjects. In addition to our previous findings of impaired neuroendocrine and appetite responses in patients with AN, we conclude that metabolic responses to ghrelin are attenuated in these patients, which tend to recover with weight gain.

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.

Similar content being viewed by others

References

  1. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999, 402: 656–60.

    Article  PubMed  CAS  Google Scholar 

  2. Ariyasu H, Takaya K, Tagami T, et al. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab 2001, 86: 4753–8.

    Article  PubMed  CAS  Google Scholar 

  3. Wren AM, Seal LJ, Cohen MA, et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001, 86: 5992.

    Article  PubMed  CAS  Google Scholar 

  4. Takaya K, Ariyasu H, Kanamoto N, et al. Ghrelin strongly stimulates growth hormone (GH) release in humans. J Clin Endocrinol Metab 2000, 85: 4908–11.

    Article  PubMed  CAS  Google Scholar 

  5. Arvat E, Maccario M, Di Vito L, et al. Endocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in humans: comparison and interactions with hexarelin, a non-natural peptidyl GHS, and GH-releasing hormone. J Clin Endocrinol Metab 2001, 86: 1169–74.

    PubMed  CAS  Google Scholar 

  6. Misra M, Miller KK, Kuo K, et al. Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents. Am J Physiol Endocrinol Metab 2005, 289: E347–56.

    Article  PubMed  CAS  Google Scholar 

  7. Heijboer AC, Pijl H, Van den Hoek AM, Havekes LM, Romijn JA, Corssmit EP. Gut-brain axis: regulation of glucose metabolism. J Neuroendocrinol 2006, 18: 883–94.

    Article  PubMed  CAS  Google Scholar 

  8. Broglio F, Arvat E, Benso A, et al. Ghrelin, a natural GH secretagogue produced by stomach, induces hyperglycemia and reduces insulin secretion in humans. J Clin Endocrinol Metab 2001, 86: 5083–6.

    Article  PubMed  CAS  Google Scholar 

  9. Broglio F, Gianotti L, Destefanis S, et al. The endocrine response to acute ghrelin administration is blunted in patients with anorexia nervosa, a ghrelin hypersecretory state. Clin Endocrinol (Oxf) 2004, 60: 592–9.

    Article  CAS  Google Scholar 

  10. Miljic D, Pekic S, Djurovic M, et al. Ghrelin has partial or no effect on appetite, growth hormone, prolactin and cortisol release in patients with anorexia nervosa. J Clin Endocrinol Metab 2006, 91: 1491–5.

    Article  PubMed  CAS  Google Scholar 

  11. Fassino S, Daga GA, Mondelli V, et al. Hormonal and metabolic responses to acute ghrelin administration in patients with bulimia nervosa. Psychoneuroendocrinology 2005, 30: 534–40.

    Article  PubMed  CAS  Google Scholar 

  12. Fujii S, Tamai H, Kumai M, Takaichi Y, Nakagawa T, Aoki TT. Impaired glucagon secretion to insulin-induced hypoglycemia in anorexia nervosa. Acta Endocrinologica (Copenh) 1989, 120: 610–5.

    CAS  Google Scholar 

  13. Damjanovic SS, Lalic NM, Pesko PM, et al. Acute effects of ghrelin on insulin secretion and glucose disposal rate in gastrectomized patients. J Clin Endocrinol Metab 2006, 91: 2574–81.

    Article  PubMed  CAS  Google Scholar 

  14. Salehi A, Dornonville de la Cour C, Hakanson R, Lundquist I. Effects of ghrelin on insulin and glucagon secretion: a study of isolated pancreatic islets and intact mice. Regul Pept 2004, 118: 143–50.

    Article  PubMed  CAS  Google Scholar 

  15. Barazzoni R, Bosutti A, Stebel M, et al. Ghrelin regulates mitochondrial-lipid metabolism gene expression and tissue fat distribution in liver and skeletal muscle. Am J Physiol Endocrinol Metab 2005, 288: E228–35.

    Article  PubMed  CAS  Google Scholar 

  16. Egido EM, Rodriguez-Gallardo J, Silvestre RA, Marco J. Inhibitory effect of ghrelin on insulin and pancreatic somatostatin secretion. Eur J Endocrinol 2002, 146: 241–4.

    Article  PubMed  CAS  Google Scholar 

  17. Müller A, Janssen A, Hofland L, et al. Blockade of the growth hormone (GH) receptor unmasks rapid GH-releasing peptide-6-mediated tissue-specific insulin resistance. J Clin Endocrinol Metab 2001, 86: 590–3.

    Article  PubMed  Google Scholar 

  18. Petretta M, Bonaduce D, Scalfi L, et al. Heart rate variability as a measure of autonomic nervous system function in anorexia nervosa. Clin Cardiol 1997, 20: 219–24.

    Article  PubMed  CAS  Google Scholar 

  19. Hotta M, Ohwada R, Katakami H, Shibasaki T, Hizuka N, Takano K. Plasma levels of intact and degraded ghrelin and their responses to glucose infusion in anorexia nervosa. J Clin Endocrinol Metab 2004, 89: 5707–12.

    Article  PubMed  CAS  Google Scholar 

  20. Broglio F, Gottero C, Prodam F, et al. Non-acylated ghrein counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. J Clin Endocrinol Metab 2004, 89: 3062–5.

    Article  PubMed  CAS  Google Scholar 

  21. Granata R, Settanni F, Trovato L, et al. Unacylated as well as acylated ghrelin promotes cell survival and inhibit apoptosis in HIT-T15 pancreatic β-cells. J Endocrinol Invest 2006, 29: RC19–22.

    Article  PubMed  CAS  Google Scholar 

  22. Fineberg SE, Merimee TJ. Acute metabolic effects of human growth hormone. Diabetes 1974, 23: 499–504.

    PubMed  CAS  Google Scholar 

  23. Bratush-Marrain PR, Smith D, DeFronzo RA. The effect of growth hormone on glucose metabolism and insulin secretion in man. J Clin Endocrinol Metab 1982, 55: 973–82.

    Article  Google Scholar 

  24. Beard JC, Halter JB, Best JD, Pfeiffer MA, Porte D Jr. Dexamethasone-induced insulin resistance enhances B cell responsiveness to glucose level in normal men. Am J Physiol 1984, 247: E592–6.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to V. Popovic MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miljic, D., Djurovic, M., Pekic, S. et al. Glucose metabolism during ghrelin infusion in patients with anorexia nervosa. J Endocrinol Invest 30, 771–775 (2007). https://doi.org/10.1007/BF03350816

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03350816

Key-words

Navigation