Literature DB >> 16314227

Metabolic and endocrine effects of physiological increments in plasma ghrelin concentrations.

Paola Lucidi1, Giuseppe Murdolo, Chiara Di Loreto, Natascia Parlanti, Arianna De Cicco, Cristina Fatone, Chiara Taglioni, Carmine Fanelli, Fabio Broglio, Ezio Ghigo, Geremia B Bolli, Fausto Santeusanio, Pierpaolo De Feo.   

Abstract

BACKGROUND: Growing evidence indicates that the administration of large amounts of ghrelin to humans increases circulating concentrations of several pituitary and adrenal hormones, induces hyperglycemia and reduces serum insulin concentrations. At present, it is not known whether physiological increments in plasma ghrelin concentrations affect glucose kinetics or hormone concentrations in humans. METHODS AND
RESULTS: We compared the effects of two- and three-fold increments in plasma ghrelin concentrations in eight healthy subjects during a 2 h intravenous infusion of 7.5 (GHRE7.5), 15 (GHRE15) pmol kg(-1) min(-1) acylated human ghrelin or placebo (PL), in a randomized double-blind study. Compared with PL (146 +/- 24 pM) plasma ghrelin concentrations increased at 120 min (p<0.001) about two-fold after GHRE7.5 (300 +/- 35 pM) and three-fold after GHRE15 (494 +/- 30 pM). GHRE15 significantly increased circulating concentrations of NEFA, GH, ACTH, epinephrine, and prolactin (p<0.01). GHRELIN7.5 significantly (p<0.01) increased only serum GH concentrations. Neither ghrelin infusions changed glucose flux or circulating concentrations of glucose, insulin, C-peptide, glucagon, IGF-1, cortisol and norepinephrine.
CONCLUSIONS: GH secretion is the only response that is stimulated by physiological increments in plasma ghrelin concentrations; about three-fold increases in plasma ghrelin concentrations are required to elicit the responses of epinephrine, prolactin, ACTH and NEFA.

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Year:  2005        PMID: 16314227     DOI: 10.1016/j.numecd.2005.02.006

Source DB:  PubMed          Journal:  Nutr Metab Cardiovasc Dis        ISSN: 0939-4753            Impact factor:   4.222


  19 in total

1.  Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans.

Authors:  Robyn A Tamboli; Joseph Antoun; Reem M Sidani; Austin Clements; Emily E Harmata; Pam Marks-Shulman; Bruce D Gaylinn; Brandon Williams; Ronald H Clements; Vance L Albaugh; Naji N Abumrad
Journal:  Diabetes Obes Metab       Date:  2017-05-31       Impact factor: 6.577

2.  Pharmacokinetics and pharmacodynamics of PF-05190457: The first oral ghrelin receptor inverse agonist to be profiled in healthy subjects.

Authors:  William S Denney; Gabriele E Sonnenberg; Santos Carvajal-Gonzalez; Theresa Tuthill; V Margaret Jackson
Journal:  Br J Clin Pharmacol       Date:  2016-10-29       Impact factor: 4.335

Review 3.  Ghrelin regulation of glucose metabolism.

Authors:  Sarah M Gray; Laura C Page; Jenny Tong
Journal:  J Neuroendocrinol       Date:  2019-04-03       Impact factor: 3.627

4.  Pharmacological characterization of the first in class clinical candidate PF-05190457: a selective ghrelin receptor competitive antagonist with inverse agonism that increases vagal afferent firing and glucose-dependent insulin secretion ex vivo.

Authors:  J Kong; J Chuddy; I A Stock; P M Loria; S V Straub; C Vage; K O Cameron; S K Bhattacharya; K Lapham; K F McClure; Y Zhang; V M Jackson
Journal:  Br J Pharmacol       Date:  2016-03-17       Impact factor: 8.739

5.  Discovery of PF-5190457, a Potent, Selective, and Orally Bioavailable Ghrelin Receptor Inverse Agonist Clinical Candidate.

Authors:  Samit K Bhattacharya; Kim Andrews; Ramsay Beveridge; Kimberly O Cameron; Chiliu Chen; Matthew Dunn; Dilinie Fernando; Hua Gao; David Hepworth; V Margaret Jackson; Vishal Khot; Jimmy Kong; Rachel E Kosa; Kimberly Lapham; Paula M Loria; Allyn T Londregan; Kim F McClure; Suvi T M Orr; Jigna Patel; Colin Rose; James Saenz; Ingrid A Stock; Gregory Storer; Maria VanVolkenburg; Derek Vrieze; Guoqiang Wang; Jun Xiao; Yingxin Zhang
Journal:  ACS Med Chem Lett       Date:  2014-02-24       Impact factor: 4.345

6.  Ghrelin directly stimulates glucagon secretion from pancreatic alpha-cells.

Authors:  Jen-Chieh Chuang; Ichiro Sakata; Daisuke Kohno; Mario Perello; Sherri Osborne-Lawrence; Joyce J Repa; Jeffrey M Zigman
Journal:  Mol Endocrinol       Date:  2011-06-30

Review 7.  Clinical review: The human experience with ghrelin administration.

Authors:  Margaret C Garin; Carrie M Burns; Shailja Kaul; Anne R Cappola
Journal:  J Clin Endocrinol Metab       Date:  2013-03-26       Impact factor: 5.958

8.  Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans.

Authors:  Jenny Tong; Ronald L Prigeon; Harold W Davis; Martin Bidlingmaier; Steven E Kahn; David E Cummings; Matthias H Tschöp; David D'Alessio
Journal:  Diabetes       Date:  2010-06-28       Impact factor: 9.461

9.  Integrating GHS into the Ghrelin System.

Authors:  Johannes D Veldhuis; Cyril Y Bowers
Journal:  Int J Pept       Date:  2010-03-18

10.  Acute effects of acylated ghrelin on salbutamol-induced metabolic actions in humans.

Authors:  A Benso; E Gramaglia; I Olivetti; M Tomelini; S Belcastro; E Calvi; A Dotta; D St-Pierre; E Ghigo; F Broglio
Journal:  Endocrine       Date:  2014-07-11       Impact factor: 3.633

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