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.
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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.
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.
Wren AM, Seal LJ, Cohen MA, et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001, 86: 5992.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Fineberg SE, Merimee TJ. Acute metabolic effects of human growth hormone. Diabetes 1974, 23: 499–504.
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.
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.
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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
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DOI: https://doi.org/10.1007/BF03350816