| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Division of Endocrinology (C.G., P.J.D.D., L.J.H., J.A.M.J.L.J., F.B., A.J.v.d.L.), Department of Internal Medicine, Erasmus MC, 3015 GE Rotterdam, The Netherlands; Division of Endocrinology (R.J.M.R.), Sheffield University, Clinical Sciences, Northern General Hospital, Sheffield S5 7AU, United Kingdom; and Division of Endocrinology and Metabolism (F.B., E.G.), Department of Internal Medicine, University of Turin, 10126 Turin, Italy
Address all correspondence and requests for reprints to: Carlotta Gauna, M.D., Department of Internal Medicine, Section of Endocrinology, Room Ee542, Erasmus MC, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. E-mail: c.gauna{at}erasmusmc.nl.
Ghrelin exerts various metabolic activities, including regulation of glucose levels in humans. To verify whether the glucose response to ghrelin reflects a modulation of an insulin-independent hepatic phenomenon, we studied glucose output by primary porcine hepatocytes in suspension culture, after incubation with acylated ghrelin (AG), unacylated ghrelin (UAG), and hexarelin (HEX). AG induced glucose output dose dependently after 20 min of incubation (P < 0.001), whereas HEX, a GH secretagogue receptor type 1a (GHS-R1a) agonist, had no effect. UAG inhibited glucose release also dose dependently and after 20 min (P < 0.001). Moreover, UAG completely reversed AG-induced glucose output (P < 0.01). Using real-time PCR, GHS-R1a gene expression was undetectable in all the hepatocyte preparations studied. The lack of efficacy of HEX, the efficacy of UAG, and the absence of GHS-R1a expression indicate the involvement of a yet uncharacterized ghrelin receptor type.
In conclusion, glucose output by primary hepatocytes is time- and dose-dependently stimulated by AG and inhibited by UAG. Moreover, UAG counteracts the stimulatory effect of AG on glucose release. These actions might be mediated by a different receptor than GHS-R1a, and apparently, we must consider AG and UAG as separate hormones that can modify each other’s actions on glucose handling, at least in the liver.
This article has been cited by other articles:
 |
|
 |
|
  L. Pacifico, E. Poggiogalle, F. Costantino, C. Anania, F. Ferraro, F. Chiarelli, and C. Chiesa Acylated and nonacylated ghrelin levels and their associations with insulin resistance in obese and normal weight children with metabolic syndrome Eur. J. Endocrinol., December 1, 2009; 161(6): 861 - 870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Walter, L. Chardon, V. Hervieu, R. Cohen, J.-A. Chayvialle, J.-Y. Scoazec, and C. Lombard-Bohas Major hyperghrelinemia in advanced well-differentiated neuroendocrine carcinomas: report of three cases Eur. J. Endocrinol., October 1, 2009; 161(4): 639 - 645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M Kiewiet, M. O van Aken, K. van der Weerd, P. Uitterlinden, A. P N Themmen, L. J Hofland, Y. B de Rijke, P. J D Delhanty, E. Ghigo, T. Abribat, et al. Effects of acute administration of acylated and unacylated ghrelin on glucose and insulin concentrations in morbidly obese subjects without overt diabetes Eur. J. Endocrinol., October 1, 2009; 161(4): 567 - 573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H St-Pierre, R. Rabasa-Lhoret, M.-E. Lavoie, A. D Karelis, I. Strychar, E. Doucet, and L. Coderre Fiber intake predicts ghrelin levels in overweight and obese postmenopausal women Eur. J. Endocrinol., July 1, 2009; 161(1): 65 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Davies, P. Kotokorpi, S. R. Eccles, S. K. Barnes, P. F. Tokarczuk, S. K. Allen, H. S. Whitworth, I. A. Guschina, B. A. J. Evans, A. Mode, et al. Ghrelin Induces Abdominal Obesity Via GHS-R-Dependent Lipid Retention Mol. Endocrinol., June 1, 2009; 23(6): 914 - 924. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Mayorov, N. Amara, J. Y. Chang, J. A. Moss, M. S. Hixon, D. I. Ruiz, M. M. Meijler, E. P. Zorrilla, and K. D. Janda Catalytic antibody degradation of ghrelin increases whole-body metabolic rate and reduces refeeding in fasting mice PNAS, November 11, 2008; 105(45): 17487 - 17492. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M A Hyatt, E A Butt, H Budge, T Stephenson, and M E Symonds Effects of maternal cold exposure and nutrient restriction on the ghrelin receptor, the GH-IGF axis, and metabolic regulation in the postnatal ovine liver Reproduction, May 1, 2008; 135(5): 723 - 732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Tong, P. T. Pfluger, and M. H. Tschop Gastric O-acyl transferase activates hunger signal to the brain PNAS, April 29, 2008; 105(17): 6213 - 6214. [Full Text] [PDF]
|
|
|
|
|
|
U. Mager, M. Kolehmainen, V. D F de Mello, U. Schwab, D. E Laaksonen, R. Rauramaa, H. Gylling, M. Atalay, L. Pulkkinen, and M. Uusitupa Expression of ghrelin gene in peripheral blood mononuclear cells and plasma ghrelin concentrations in patients with metabolic syndrome. Eur. J. Endocrinol., April 1, 2008; 158(4): 499 - 510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H St-Pierre, J.-P. Bastard, L. Coderre, M. Brochu, A. D Karelis, M.-E. Lavoie, F. Malita, J. Fontaine, D. Mignault, K. Cianflone, et al. Association of acylated ghrelin profiles with chronic inflammatory markers in overweight and obese postmenopausal women: a MONET study Eur. J. Endocrinol., October 1, 2007; 157(4): 419 - 426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Barazzoni, M. Zanetti, C. Ferreira, P. Vinci, A. Pirulli, M. Mucci, F. Dore, M. Fonda, B. Ciocchi, L. Cattin, et al. Relationships between Desacylated and Acylated Ghrelin and Insulin Sensitivity in the Metabolic Syndrome J. Clin. Endocrinol. Metab., October 1, 2007; 92(10): 3935 - 3940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Gauna, R. M. Kiewiet, J. A. M. J. L. Janssen, B. van de Zande, P. J. D. Delhanty, E. Ghigo, L. J. Hofland, A. P. N. Themmen, and A. J. van der Lely Unacylated ghrelin acts as a potent insulin secretagogue in glucose-stimulated conditions Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E697 - E704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. D. Delhanty, P. M. van Koetsveld, C. Gauna, B. van de Zande, G. Vitale, L. J. Hofland, and A. J. van der Lely Ghrelin and its unacylated isoform stimulate the growth of adrenocortical tumor cells via an anti-apoptotic pathway Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E302 - E309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D Kineman, M. D Gahete, and R. M Luque Identification of a mouse ghrelin gene transcript that contains intron 2 and is regulated in the pituitary and hypothalamus in response to metabolic stress J. Mol. Endocrinol., May 1, 2007; 38(5): 511 - 521. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rauh, M. Groschl, and W. Rascher Simultaneous Quantification of Ghrelin and Desacyl-Ghrelin by Liquid Chromatography-Tandem Mass Spectrometry in Plasma, Serum, and Cell Supernatants Clin. Chem., May 1, 2007; 53(5): 902 - 910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Granata, F. Settanni, L. Biancone, L. Trovato, R. Nano, F. Bertuzzi, S. Destefanis, M. Annunziata, M. Martinetti, F. Catapano, et al. Acylated and Unacylated Ghrelin Promote Proliferation and Inhibit Apoptosis of Pancreatic {beta}-Cells and Human Islets: Involvement of 3',5'-Cyclic Adenosine Monophosphate/Protein Kinase A, Extracellular Signal-Regulated Kinase 1/2, and Phosphatidyl Inositol 3-Kinase/Akt Signaling Endocrinology, February 1, 2007; 148(2): 512 - 529. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. St-Pierre, A. D. Karelis, L. Coderre, F. Malita, J. Fontaine, D. Mignault, M. Brochu, J.-P. Bastard, K. Cianflone, E. Doucet, et al. Association of Acylated and Nonacylated Ghrelin with Insulin Sensitivity in Overweight and Obese Postmenopausal Women J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 264 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Dezaki, H. Sone, M. Koizumi, M. Nakata, M. Kakei, H. Nagai, H. Hosoda, K. Kangawa, and T. Yada Blockade of Pancreatic Islet-Derived Ghrelin Enhances Insulin Secretion to Prevent High-Fat Diet-Induced Glucose Intolerance Diabetes, December 1, 2006; 55(12): 3486 - 3493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A Martos-Moreno, V. Barrios, L. Soriano-Guillen, and J. Argente Relationship between adiponectin levels, acylated ghrelin levels, and short-term body mass index changes in children with diabetes mellitus type 1 at diagnosis and after insulin therapy. Eur. J. Endocrinol., November 1, 2006; 155(5): 757 - 761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. ThidarMyint, H. Yoshida, T. Ito, and H. Kuwayama Dose-dependent response of plasma ghrelin and growth hormone concentrations to bovine ghrelin in Holstein heifers. J. Endocrinol., June 1, 2006; 189(3): 655 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Martini, R. Fernandez-Fernandez, S. Tovar, V. M. Navarro, E. Vigo, M. J. Vazquez, J. S. Davies, N. M. Thompson, E. Aguilar, L. Pinilla, et al. Comparative Analysis of the Effects of Ghrelin and Unacylated Ghrelin on Luteinizing Hormone Secretion in Male Rats Endocrinology, May 1, 2006; 147(5): 2374 - 2382. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Iwakura, K. Hosoda, C. Son, J. Fujikura, T. Tomita, M. Noguchi, H. Ariyasu, K. Takaya, H. Masuzaki, Y. Ogawa, et al. Analysis of Rat Insulin II Promoter-Ghrelin Transgenic Mice and Rat Glucagon Promoter-Ghrelin Transgenic Mice J. Biol. Chem., April 15, 2005; 280(15): 15247 - 15256. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
