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Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans.
J Clin Endocrinol Metab. 2004 Jun; 89(6):3062-5.JC

Abstract

Ghrelin possesses strong GH-releasing activity but also other endocrine activities including stimulation of PRL and ACTH secretion, modulation of insulin secretion and glucose metabolism. It is assumed that the GH secretagogue (GHS) receptor (GHS-R) 1a mediates ghrelin actins provided its acylation in Serine 3; in fact, acylated ghrelin only is able to exert endocrine activities. Acylated ghrelin (AG) is present in serum at a 2.5 fold lower concentration than unacylated ghrelin (UAG). UAG, however, is not biologically inactive; it shares with AG some non-endocrine actions like cardiovascular effects, modulation of cell proliferation and even some influence on adipogenesis. Thus, these actions are likely to be mediated by GHS-R subtypes able to bind ghrelin independently of its acylation. In order to further clarify whether UAG is really devoid of any endocrine action, we studied the interaction of the combined administration of AG and UAG (1.0 microg/kg i.v.) in 6 normal young volunteers (age [mean +/- SE]: 25.4 +/- 1.2 yr; BMI: 22.3 +/- 1.0 kg/m2). As expected, AG induced marked increase (p < 0.01) in circulating GH, PRL, ACTH and cortisol levels. AG administration was also followed by a decrease in insulin levels (-285.4 +/- 64.8 mU*min/l; p < 0.05) and an increase in plasma glucose levels (1068.4 +/- 390.4 mg*min/dl; p < 0.01). UAG alone did not induce any change in these parameters. UAG also failed to modify the GH, PRL, ACTH and cortisol responses to AG. However, when UAG was co-administered together with AG, no significant change in insulin (-0.5 +/- 40.9 mU*min/l) and glucose levels (455.9 +/- 88.3 mg*min/dl) was recorded anymore, indicating that the insulin and glucose response to AG has been abolished by UAG. In conclusion, non-acylated ghrelin does not affect the GH, PRL, and ACTH response to acylated ghrelin but is able to antagonize the effects of acylated ghrelin on insulin secretion and glucose levels. These findings indicate that unacylated ghrelin is metabolically active and is likely to counterbalance the influence of acylated ghrelin on insulin secretion and glucose metabolism. As GHS-R1a is not bound by unacylated ghrelin, these findings suggest that GHS receptor subtypes mediate the metabolic actions of both acylated and unacylated ghrelin.

Authors+Show Affiliations

Division of Endocrinology, Department of Internal Medicine, Erasmus University of Rotterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15181099

Citation

Broglio, F, et al. "Non-acylated Ghrelin Counteracts the Metabolic but Not the Neuroendocrine Response to Acylated Ghrelin in Humans." The Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 6, 2004, pp. 3062-5.
Broglio F, Gottero C, Prodam F, et al. Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. J Clin Endocrinol Metab. 2004;89(6):3062-5.
Broglio, F., Gottero, C., Prodam, F., Gauna, C., Muccioli, G., Papotti, M., Abribat, T., Van Der Lely, A. J., & Ghigo, E. (2004). Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. The Journal of Clinical Endocrinology and Metabolism, 89(6), 3062-5.
Broglio F, et al. Non-acylated Ghrelin Counteracts the Metabolic but Not the Neuroendocrine Response to Acylated Ghrelin in Humans. J Clin Endocrinol Metab. 2004;89(6):3062-5. PubMed PMID: 15181099.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. AU - Broglio,F, AU - Gottero,C, AU - Prodam,F, AU - Gauna,C, AU - Muccioli,G, AU - Papotti,M, AU - Abribat,T, AU - Van Der Lely,A J, AU - Ghigo,E, PY - 2004/6/8/pubmed PY - 2004/7/20/medline PY - 2004/6/8/entrez SP - 3062 EP - 5 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 89 IS - 6 N2 - Ghrelin possesses strong GH-releasing activity but also other endocrine activities including stimulation of PRL and ACTH secretion, modulation of insulin secretion and glucose metabolism. It is assumed that the GH secretagogue (GHS) receptor (GHS-R) 1a mediates ghrelin actins provided its acylation in Serine 3; in fact, acylated ghrelin only is able to exert endocrine activities. Acylated ghrelin (AG) is present in serum at a 2.5 fold lower concentration than unacylated ghrelin (UAG). UAG, however, is not biologically inactive; it shares with AG some non-endocrine actions like cardiovascular effects, modulation of cell proliferation and even some influence on adipogenesis. Thus, these actions are likely to be mediated by GHS-R subtypes able to bind ghrelin independently of its acylation. In order to further clarify whether UAG is really devoid of any endocrine action, we studied the interaction of the combined administration of AG and UAG (1.0 microg/kg i.v.) in 6 normal young volunteers (age [mean +/- SE]: 25.4 +/- 1.2 yr; BMI: 22.3 +/- 1.0 kg/m2). As expected, AG induced marked increase (p < 0.01) in circulating GH, PRL, ACTH and cortisol levels. AG administration was also followed by a decrease in insulin levels (-285.4 +/- 64.8 mU*min/l; p < 0.05) and an increase in plasma glucose levels (1068.4 +/- 390.4 mg*min/dl; p < 0.01). UAG alone did not induce any change in these parameters. UAG also failed to modify the GH, PRL, ACTH and cortisol responses to AG. However, when UAG was co-administered together with AG, no significant change in insulin (-0.5 +/- 40.9 mU*min/l) and glucose levels (455.9 +/- 88.3 mg*min/dl) was recorded anymore, indicating that the insulin and glucose response to AG has been abolished by UAG. In conclusion, non-acylated ghrelin does not affect the GH, PRL, and ACTH response to acylated ghrelin but is able to antagonize the effects of acylated ghrelin on insulin secretion and glucose levels. These findings indicate that unacylated ghrelin is metabolically active and is likely to counterbalance the influence of acylated ghrelin on insulin secretion and glucose metabolism. As GHS-R1a is not bound by unacylated ghrelin, these findings suggest that GHS receptor subtypes mediate the metabolic actions of both acylated and unacylated ghrelin. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/15181099/Non_acylated_ghrelin_counteracts_the_metabolic_but_not_the_neuroendocrine_response_to_acylated_ghrelin_in_humans_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2003-031964 DB - PRIME DP - Unbound Medicine ER -