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Ghrelin, A New Gastrointestinal Endocrine Peptide that Stimulates Insulin Secretion: Enteric Distribution, Ontogeny, Influence of Endocrine, and Dietary Manipulations

Department of Surgery (H.-M.L., G.W., E.W.E., G.H.G.), University of Texas Medical Branch, Galveston, Texas 77555; and Department of Molecular Genetics (M.K.), Institute of Life Science, Karume-University, Karume, Fukuoka 839-0861, Japan

Ghrelin, an endogenous ligand for the GH secretagogue receptor was characterized recently from extracts of rat stomach. We describe the enteric distribution of ghrelin, ontogeny of stomach ghrelin gene expression, effects of dietary and endocrine manipulations, and vagotomy on stomach ghrelin mRNA and peptide levels and secretion in the rat. Ghrelin expression was examined by Northern blotting. Tissue and plasma ghrelin levels were measured by RIA. A gradient of ghrelin production occurs in the rat gastrointestinal tract with the highest ghrelin expression and peptide levels in the mucosal layer of the stomach-fundus and the lowest levels in the colon. Ghrelin was not detectable in the fetal stomach and increased progressively after birth especially during the second and third postnatal weeks. Plasma ghrelin levels also increased in parallel with stomach ghrelin levels postnatally. Exogenous GH treatment decreased stomach ghrelin expression significantly. A high-fat diet decreased plasma ghrelin levels, whereas a low-protein diet increased plasma ghrelin levels significantly. Intravenous administration of ghrelin stimulates gastrin and insulin secretion. Our findings indicate that ghrelin is an important stomach hormone sensitive to nutritional intake; ghrelin may link enteric nutrition with secretion of GH, insulin, and gastrin.

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				M. Volante, E. Allia, E. Fulcheri, P. Cassoni, E. Ghigo, G. Muccioli, and M. Papotti Ghrelin in Fetal Thyroid and Follicular Tumors and Cell Lines: Expression and Effects on Tumor Growth Am. J. Pathol., February 1, 2003; 162(2): 645 - 654. [Abstract] [Full Text] [PDF]

				V. Sibilia, G. Rindi, F. Pagani, D. Rapetti, V. Locatelli, A. Torsello, N. Campanini, R. Deghenghi, and C. Netti Ghrelin Protects Against Ethanol-Induced Gastric Ulcers in Rats: Studies on the Mechanisms of Action Endocrinology, January 1, 2003; 144(1): 353 - 359. [Abstract] [Full Text] [PDF]

				G. Schaller, A. Schmidt, J. Pleiner, W. Woloszczuk, M. Wolzt, and A. Luger Plasma Ghrelin Concentrations Are Not Regulated by Glucose or Insulin: A Double-Blind, Placebo-Controlled Crossover Clamp Study Diabetes, January 1, 2003; 52(1): 16 - 20. [Abstract] [Full Text] [PDF]

				H. Hosoda, M. Kojima, and K. Kangawa Ghrelin and the Regulation of Food Intake and Energy Balance Mol. Interv., December 1, 2002; 2(8): 494 - 503. [Abstract] [Full Text]

				A. DelParigi, M. Tschop, M. L. Heiman, A. D. Salbe, B. Vozarova, S. M. Sell, J. C. Bunt, and P. A. Tataranni High Circulating Ghrelin: A Potential Cause for Hyperphagia and Obesity in Prader-Willi Syndrome J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5461 - 5464. [Abstract] [Full Text] [PDF]

				S. R. Cunha and K. E. Mayo Ghrelin and Growth Hormone (GH) Secretagogues Potentiate GH-Releasing Hormone (GHRH)-Induced Cyclic Adenosine 3',5'-Monophosphate Production in Cells Expressing Transfected GHRH and GH Secretagogue Receptors Endocrinology, December 1, 2002; 143(12): 4570 - 4582. [Abstract] [Full Text] [PDF]

				C. Schofl, R. Horn, T. Schill, H. W. Schlosser, M. J. Muller, and G. Brabant Circulating Ghrelin Levels in Patients with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4607 - 4610. [Abstract] [Full Text] [PDF]

				H. Ariyasu, K. Takaya, H. Hosoda, H. Iwakura, K. Ebihara, K. Mori, Y. Ogawa, K. Hosoda, T. Akamizu, M. Kojima, et al. Delayed Short-Term Secretory Regulation of Ghrelin in Obese Animals: Evidenced by a Specific RIA for the Active Form of Ghrelin Endocrinology, September 1, 2002; 143(9): 3341 - 3350. [Abstract] [Full Text] [PDF]