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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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