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The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 10 4753-4758
Copyright © 2001 by The Endocrine Society

Other Original Articles

Stomach Is a Major Source of Circulating Ghrelin, and Feeding State Determines Plasma Ghrelin-Like Immunoreactivity Levels in Humans

Hiroyuki Ariyasu, Kazuhiko Takaya, Tetsuya Tagami, Yoshihiro Ogawa, Kiminori Hosoda, Takashi Akamizu, Michio Suda, Toshikiyo Koh, Koshi Natsui, Shigetake Toyooka, Gotaro Shirakami, Takeshi Usui, Akira Shimatsu, Kentaro Doi, Hiroshi Hosoda, Masayasu Kojima, Kenji Kangawa and Kazuwa Nakao

Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine (H.A., K.T., Y.O., K.H., T.A., K.D., K.N.), Kyoto 606-8507; Clinical Research Institute, Center for Endocrine and Metabolic Diseases, Kyoto National Hospital (T.T., T.U., A.S.), Kyoto 612-8555; Division of Endocrinology, Department of Medicine, Kyoto City Hospital (M.S., T.K.), Kyoto 604-8845; Department of Internal Medicine, Fukui Red Cross Hospital (K.N., S.T.), Fukui 918-8501; Department of Anesthesia, Kyoto University Hospital (G.S.), Kyoto 606-8507; and Department of Biochemistry, National Cardiovascular Center Research Institute (K.D., H.H., M.K., K.K.), Osaka 565-8565, Japan

Address all correspondence and requests for reprints to: Kazuhiko Takaya, M.D., Ph.D., Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. E-mail: ktakaya{at}kuhp.kyoto-u.ac.jp

Abstract

Ghrelin, an endogenous ligand for the GH secretagogue receptor, was isolated from rat stomach and is involved in a novel system for regulating GH release. Although previous studies in rodents suggest that ghrelin is also involved in energy homeostasis and that ghrelin secretion is influenced by feeding, little is known about plasma ghrelin in humans. To address this issue, we studied plasma ghrelin-like immunoreactivity levels and elucidated the source of circulating ghrelin and the effects of feeding state on plasma ghrelin-like immunoreactivity levels in humans. The plasma ghrelin-like immunoreactivity concentration in normal humans measured by a specific RIA was 166.0 ± 10.1 fmol/ml. Northern blot analysis of various human tissues identified ghrelin mRNA found most abundantly in the stomach and plasma ghrelin-like immunoreactivity levels in totally gastrectomized patients were reduced to 35% of those in normal controls. Plasma ghrelin-like immunoreactivity levels were increased by 31% after 12-h fasting and reduced by 22% immediately after habitual feeding. In patients with anorexia nervosa, plasma ghrelin-like immunoreactivity levels were markedly elevated compared with those in normal controls (401.2 ± 58.4 vs. 192.8 ± 19.4 fmol/ml) and were negatively correlated with body mass indexes. We conclude that the stomach is a major source of circulating ghrelin and that plasma ghrelin-like immunoreactivity levels reflect acute and chronic feeding states in humans.




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 EndocrinologyHome page
F. Rubino, P. Zizzari, C. Tomasetto, M.-T. Bluet-Pajot, A. Forgione, M. Vix, D. Grouselle, and J. Marescaux
The Role of the Small Bowel in the Regulation of Circulating Ghrelin Levels and Food Intake in the Obese Zucker Rat
Endocrinology, April 1, 2005; 146(4): 1745 - 1751.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
C. De Vriese, F. Gregoire, P. De Neef, P. Robberecht, and C. Delporte
Ghrelin Is Produced by the Human Erythroleukemic HEL Cell Line and Involved in an Autocrine Pathway Leading to Cell Proliferation
Endocrinology, March 1, 2005; 146(3): 1514 - 1522.
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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
E. Keen-Rhinehart and T. J. Bartness
Peripheral ghrelin injections stimulate food intake, foraging, and food hoarding in Siberian hamsters
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2005; 288(3): R716 - R722.
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 Am. J. Clin. Nutr.Home page
W. A. Blom, A. Stafleu, C. de Graaf, F. J Kok, G. Schaafsma, and H. F. Hendriks
Ghrelin response to carbohydrate-enriched breakfast is related to insulin
Am. J. Clinical Nutrition, February 1, 2005; 81(2): 367 - 375.
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 J EndocrinolHome page
K. Wynne, S. Stanley, B. McGowan, and S. Bloom
Appetite control
J. Endocrinol., February 1, 2005; 184(2): 291 - 318.
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U. Espelund, T. K. Hansen, K. Hojlund, H. Beck-Nielsen, J. T. Clausen, B. S. Hansen, H. Orskov, J. O. L. Jorgensen, and J. Frystyk
Fasting Unmasks a Strong Inverse Association between Ghrelin and Cortisol in Serum: Studies in Obese and Normal-Weight Subjects
J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 741 - 746.
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K. E. Foster-Schubert, A. McTiernan, R. S. Frayo, R. S. Schwartz, K. B. Rajan, Y. Yasui, S. S. Tworoger, and D. E. Cummings
Human Plasma Ghrelin Levels Increase during a One-Year Exercise Program
J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 820 - 825.
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 EndocrinologyHome page
J. Overduin, R. S. Frayo, H. J. Grill, J. M. Kaplan, and D. E. Cummings
Role of the Duodenum and Macronutrient Type in Ghrelin Regulation
Endocrinology, February 1, 2005; 146(2): 845 - 850.
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 GutHome page
A Asakawa, A Inui, M Fujimiya, R Sakamaki, N Shinfuku, Y Ueta, M M Meguid, and M Kasuga
Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin
Gut, January 1, 2005; 54(1): 18 - 24.
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H. Osawa, M. Nakazato, Y. Date, H. Kita, H. Ohnishi, H. Ueno, T. Shiiya, K. Satoh, Y. Ishino, and K. Sugano
Impaired Production of Gastric Ghrelin in Chronic Gastritis Associated with Helicobacter pylori
J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 10 - 16.
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 EndocrinologyHome page
H. Ariyasu, K. Takaya, H. Iwakura, H. Hosoda, T. Akamizu, Y. Arai, K. Kangawa, and K. Nakao
Transgenic Mice Overexpressing Des-Acyl Ghrelin Show Small Phenotype
Endocrinology, January 1, 2005; 146(1): 355 - 364.
[Abstract] [Full Text] [PDF]

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 Alcohol AlcoholHome page
D.-J. KIM, S.-J. YOON, B. CHOI, T.-S. KIM, Y. S. WOO, W. KIM, H. MYRICK, B. S. PETERSON, Y. B. CHOI, Y.-K. KIM, et al.
INCREASED FASTING PLASMA GHRELIN LEVELS DURING ALCOHOL ABSTINENCE
Alcohol Alcohol., January 1, 2005; 40(1): 76 - 79.
[Abstract] [Full Text] [PDF]

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 DiabetesHome page
K. Dezaki, H. Hosoda, M. Kakei, S. Hashiguchi, M. Watanabe, K. Kangawa, and T. Yada
Endogenous Ghrelin in Pancreatic Islets Restricts Insulin Release by Attenuating Ca2+ Signaling in {beta}-Cells: Implication in the Glycemic Control in Rodents
Diabetes, December 1, 2004; 53(12): 3142 - 3151.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
T. Y. Jeon, S. Lee, H. H. Kim, Y. J. Kim, H. C. Son, D. H. Kim, and M. S. Sim
Changes in Plasma Ghrelin Concentration Immediately after Gastrectomy in Patients with Early Gastric Cancer
J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5392 - 5396.
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M. Hotta, R. Ohwada, H. Katakami, T. Shibasaki, N. Hizuka, and K. Takano
Plasma Levels of Intact and Degraded Ghrelin and Their Responses to Glucose Infusion in Anorexia Nervosa
J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5707 - 5712.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
S. H. Adams, W. B. Won, S. E. Schonhoff, A. B. Leiter, and J. R. Paterniti Jr.
Effects of Peptide YY[3-36] on Short-Term Food Intake in Mice Are Not Affected by Prevailing Plasma Ghrelin Levels
Endocrinology, November 1, 2004; 145(11): 4967 - 4975.
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C. Gauna, F. M. Meyler, J. A. M. J. L. Janssen, P. J. D. Delhanty, T. Abribat, P. van Koetsveld, L. J. Hofland, F. Broglio, E. Ghigo, and A. J. van der Lely
Administration of Acylated Ghrelin Reduces Insulin Sensitivity, Whereas the Combination of Acylated Plus Unacylated Ghrelin Strongly Improves Insulin Sensitivity
J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 5035 - 5042.
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M. Arosio, C. L. Ronchi, P. Beck-Peccoz, C. Gebbia, C. Giavoli, V. Cappiello, D. Conte, and M. Peracchi
Effects of Modified Sham Feeding on Ghrelin Levels in Healthy Human Subjects
J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 5101 - 5104.
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 Proc. Natl. Acad. Sci. USAHome page
S. Helmling, C. Maasch, D. Eulberg, K. Buchner, W. Schroder, C. Lange, S. Vonhoff, B. Wlotzka, M. H. Tschop, S. Rosewicz, et al.
Inhibition of ghrelin action in vitro and in vivo by an RNA-Spiegelmer
PNAS, September 7, 2004; 101(36): 13174 - 13179.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
P. Koutkia, B. Canavan, J. Breu, M. L. Johnson, and S. K. Grinspoon
Nocturnal ghrelin pulsatility and response to growth hormone secretagogues in healthy men
Am J Physiol Endocrinol Metab, September 1, 2004; 287(3): E506 - E512.
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 J. Clin. Endocrinol. Metab.Home page
S. Grinspoon, K. K. Miller, D. B. Herzog, K. A. Grieco, and A. Klibanski
Effects of Estrogen and Recombinant Human Insulin-Like Growth Factor-I on Ghrelin Secretion in Severe Undernutrition
J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3988 - 3993.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
J.-P. Chanoine and A. C. K. Wong
Ghrelin Gene Expression Is Markedly Higher in Fetal Pancreas Compared with Fetal Stomach: Effect of Maternal Fasting
Endocrinology, August 1, 2004; 145(8): 3813 - 3820.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
D. E. Cummings, R. S. Frayo, C. Marmonier, R. Aubert, and D. Chapelot
Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues
Am J Physiol Endocrinol Metab, August 1, 2004; 287(2): E297 - E304.
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 Arch SurgHome page
E. Lin, N. Gletsu, K. Fugate, D. McClusky, L. H. Gu, J.-L. Zhu, B. J. Ramshaw, D. A. Papanicolaou, T. R. Ziegler, and C. D. Smith
The Effects of Gastric Surgery on Systemic Ghrelin Levels in the Morbidly Obese
Arch Surg, July 1, 2004; 139(7): 780 - 784.
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 Am. J. Clin. Nutr.Home page
C. de Graaf, W. A. Blom, P. A. Smeets, A. Stafleu, and H. F. Hendriks
Biomarkers of satiation and satiety
Am. J. Clinical Nutrition, June 1, 2004; 79(6): 946 - 961.
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 Endocr. Rev.Home page
A. J. van der Lely, M. Tschop, M. L. Heiman, and E. Ghigo
Biological, Physiological, Pathophysiological, and Pharmacological Aspects of Ghrelin
Endocr. Rev., June 1, 2004; 25(3): 426 - 457.
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 J. Clin. Endocrinol. Metab.Home page
D. E. Cummings, J. Overduin, and K. E. Foster-Schubert
Gastric Bypass for Obesity: Mechanisms of Weight Loss and Diabetes Resolution
J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2608 - 2615.
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 EndocrinologyHome page
M. R. Druce, C. J. Small, and S. R. Bloom
Minireview: Gut Peptides Regulating Satiety
Endocrinology, June 1, 2004; 145(6): 2660 - 2665.
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 Am. J. Physiol. Endocrinol. Metab.Home page
A. Dzaja, M. A. Dalal, H. Himmerich, M. Uhr, T. Pollmacher, and A. Schuld
Sleep enhances nocturnal plasma ghrelin levels in healthy subjects
Am J Physiol Endocrinol Metab, June 1, 2004; 286(6): E963 - E967.
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G. Marchesini, G. Bianchi, P. Lucidi, N. Villanova, M. Zoli, and P. De Feo
Plasma Ghrelin Concentrations, Food Intake, and Anorexia in Liver Failure
J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2136 - 2141.
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 J. Clin. Endocrinol. Metab.Home page
F. Broglio, C. Gottero, P. Van Koetsveld, F. Prodam, S. Destefanis, A. Benso, C. Gauna, L. Hofland, E. Arvat, A. J. van der Lely, et al.
Acetylcholine Regulates Ghrelin Secretion in Humans
J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2429 - 2433.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
S. V. Angeloni, N. Glynn, G. Ambrosini, M. J. Garant, J. Dee Higley, S. Suomi, and B. C. Hansen
Characterization of the Rhesus Monkey Ghrelin Gene and Factors Influencing Ghrelin Gene Expression and Fasting Plasma Levels
Endocrinology, May 1, 2004; 145(5): 2197 - 2205.
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 J ANIM SCIHome page
H. Miura, N. Tsuchiya, I. Sasaki, M. Kikuchi, M. Kojima, K. Kangawa, Y. Hasegawa, and Y. Ohnami
Changes in plasma ghrelin and growth hormone concentrations in mature Holstein cows and three-month-old calves
J Anim Sci, May 1, 2004; 82(5): 1329 - 1333.
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 J. Clin. Endocrinol. Metab.Home page
E. Doucet, M. Pomerleau, and M.-E. Harper
Fasting and Postprandial Total Ghrelin Remain Unchanged after Short-Term Energy Restriction
J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1727 - 1732.
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 J. Clin. Endocrinol. Metab.Home page
T. Tagami, N. Satoh, T. Usui, K. Yamada, A. Shimatsu, and H. Kuzuya
Adiponectin in Anorexia Nervosa and Bulimia Nervosa
J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1833 - 1837.
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N. Wierup, S. Yang, R. J. McEvilly, H. Mulder, and F. Sundler
Ghrelin Is Expressed in a Novel Endocrine Cell Type in Developing Rat Islets and Inhibits Insulin Secretion from INS-1 (832/13) Cells
J. Histochem. Cytochem., March 1, 2004; 52(3): 301 - 310.
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 J. Clin. Endocrinol. Metab.Home page
H. S. Callahan, D. E. Cummings, M. S. Pepe, P. A. Breen, C. C. Matthys, and D. S. Weigle
Postprandial Suppression of Plasma Ghrelin Level Is Proportional to Ingested Caloric Load but Does Not Predict Intermeal Interval in Humans
J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1319 - 1324.
[Abstract] [Full Text] [PDF]

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 FASEB J.Home page
A. INUI, A. ASAKAWA, C. Y. BOWERS, G. MANTOVANI, A. LAVIANO, M. M. MEGUID, and M. FUJIMIYA
Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ
FASEB J, March 1, 2004; 18(3): 439 - 456.
[Abstract] [Full Text] [PDF]

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 Rheumatology (Oxford)Home page
M. Otero, R. Nogueiras, F. Lago, C. Dieguez, J. J. Gomez-Reino, and O. Gualillo
Chronic inflammation modulates ghrelin levels in humans and rats
Rheumatology, March 1, 2004; 43(3): 306 - 310.
[Abstract] [Full Text] [PDF]


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