2003 Fiscal Year Final Research Report Summary
Generation and analysis of transgenic mice overexpressing an acylated peptide, ghrelin
| Project/Area Number |
14571080
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
TAKAYA Kazuhiko KYOTO UNIVERSITY, Graduate School of Medicine, assistant professor, 医学研究科, 助手 (50291901)
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| Project Period (FY) |
2002 – 2003
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| Keywords | gene / transgenic mice / growth hormone / ghrelin / overexpression |
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| Research Abstract |
We succeeded in generating of several lines of transgenic mice overexpressing prepro-ghrelin mRNA, using a various promoters. They are now under analysis and we found that overexpressed ghrelin or des-acyl ghrelin might some effects on the endogenous GH-IGF-I axis and/or glucose metabolism in these transgenic mice. In parallel with the study, we also investigated the secretory regulation of and the effects of ghrelin. In obese animals, the response of ghrelin secretion to fasting was delayed and the delay was restored by insulin injection, suggesting that their high levels of blood sugar may be the cause of the delay. Moreover, glucose injection in mice was revealed to reduce plasma ghrelin levels, supporting that the hypothesis that glucose and/or insulin regulate ghrelin secretion. We also examined plasma ghrelin levels in patients with renal failure and elucidated that they are highly elevated in them compared to those in normal subjects. Bilateral nephrectoiny in mice caused marked increase in the plasma ghrelin levels in mice without any changes in ghrelin mRNA and peptide levels in the stomach, suggesting that the kidney is an important site for clearance of ghrelin. Furthermore, we examined ghrelin levels in human islet cell tumors and found augmented expression of ghrelin in a case of glucagonoma with multiple endocrine naoplasia type I. As described above, we advanced in the generation and analysis of ghrelin-transgenic mice and the study in the secretory regulation of and the effects of ghrelin.
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Research Products
(12 results)
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[Publications] Ariyasu H, Takaya K, Hosoda H, Iwakura H, Ebihara K, Mon K, Ogawa Y, Hosoda K, Akamizu T, Kojima M, Kangawa K, Nakao K: "Delayed short-term secretory regulatior of ghrelin in obese animals: evidenced by a specific RIA for the active form of ghrelin."Endocrinology. 143. 3341-3350 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Iwakura H, Hosoda K, Doi R, Komoto I, Nishimura H, Son C, Fujikura J, Tomita T, Takaya K, Ogawa Y, Hayashi T, lnoue G, Akamizu T, Hosoda H, Kojima M, Kangawa K, Imanuira M, Nakao K: "Ghrelin expression in islet cell tumors: augmented expression of ghrelin in a case of glucagonoma with multiple endocrine neoplasm type I."J Clin Endocrinol Metab. 87. 4885-4888 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Yoshimoto A, Mon K, Sugawara A, Mukoyama M, Yahata K, Suganami T, Takaya K, Hosoda H, Kojima M, Kangawa K, Nakao K: "Plasma ghrelin and desacyl ghrelin concentrations in renal failure."J Am Soc Nephrol. 13. 2748-2752 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Akamizu T, Takaya K, Irako T, Hosoda H, Teramukai S, Matsuyama A, Tada H, Miura K, Shimizu A, Fukushima M, Yakode M, Tanaka K, Kangawa K: "Pharmacokinetics, safety, and endocrine and appetite effects of ghrelin administration in young healthy subjects."Eur J Endocrinol. 150. 447-455 (2004)
Description
「研究成果報告書概要(欧文)」より
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