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Application of ghrelin for diagnosis and treatment of endocrine and metabolic diseases.

Research Project

Project/Area Number 14370331
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionKurume University

Principal Investigator

KOJIMA Masayasu  Kurume University, Institute of Life Science, Professor, 分子生命科学研究所, 教授 (20202062)

Co-Investigator(Kenkyū-buntansha) KANGAWA Kenji  National Cardiovascular Center, Research Institute, Head, 生化学部, 部長(研究職) (00112417)
NISHI Yoshihiro  Kurume University, Institute of Life Science, Assistance, 分子生命科学研究所, 助手 (20352122)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 2003: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2002: ¥10,800,000 (Direct Cost: ¥10,800,000)
Keywordsghrelin / growth hormone / appetite regulation / stomach / acyl acid / octanoic acid / プラダー・ヴィリー症候群 / 成長ホルモン / 摂食調節 / 胃 / 脂肪酸
Research Abstract

Our group discovered human and rat ghrelins from stomach. Ghrelin. is a novel hormone, which stimulates growth hormone (GH) release and appetite. The third amino-acid serine from the N-terminal end is modified by a lipid n-octanoic acid and this modification is essential for ghrelin activity. In the period of this grant, we performed following research on ghrelin.
1, Molecular forms of ghrelin in human stomach In human stomach ghrelin existed mainly as the n-octanoyl modified form. In addition, we found four minor molecular forms of ghrelin. Thus, in human stomach ghrelin existed as multiple forms with various amino-acid lengths and acyl-modifications.
2, We examined the contribution of stomach for the production of ghrelin. We measured plasma ghrelin concentrations before and after total gastrectomy operation. Plasma ghrelin concentration was decreased approximately to half that of before the operation, and gradually increased to near normal level. This result indicates that intestinal and pancreatic ghrelins compensate the loss of gastric ghrelin.
3, Purifications and structures of non-mammalian ghrelins We determined the structures of amphibian, bird, and fish ghrelins, and found that ghrelin existed not only in mammals but also in all vertebrate species. Moreover, acyl-modification of ghrelin is found in amphibian, bird, and fish ghrelins, as like mammalian ghrelins. Thus, ghrelin is a well-conserved peptide hormone that is essential for survival of vertebrates.
4, Creation of ghrelin null-mice We tried to create ghrelin null-mice and succeeded in creating ghrelin null-mice. We are now investigating their phenotypes.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] H.Kaiya et al.: "Peptide purification, complementary deoxyribonucleic acid (DNA) and genomic DNA cloning, and functional characterization of ghrelin in rainbow trout"Endocrinology. 144. 5215-5226 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Kaiya et al.: "Amidated fish ghrelin: purification, cDNA cloning in the Japanese eel and its biological activity"Journal of Endocrinology. 176. 415-423 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Choi et al.: "The role of ghrelin and growth hormone secretagogues receptor on rat adipogenesis"Endocrinology. 144. 754-759 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Hosoda et al.: "Structural divergence of human ghrelin. Identification of multiple ghrelin-derived molecules produced by post-translational processing"Journal of Biological Chemistry. 278. 64-70 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Nakahara et al.: "Effect of chronic treatments with ghrelin on milk secretion in lactating rats"Biochem.Biophys.Res.Commun.. 303. 751-755 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Tanaka et al.: "Ghrelin is involved in the decidualization of human endometrial stromal cells"J Clin Endocrinol Metab. 88. 2335-2340 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Choi K, Roh SG, Hong YH, Shrestha YB, Hishikawa D, Chen C, Kojima M, Kangawa K, Sasaki S.: "The role of ghrelin and growth hormone secretagogues receptor on rat adipogenesis."Endocrinology. 144(3). 754-759 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hosoda H, Kojima M, Mizushima T, Shimizu 5, Kangawa K.: "Structural divergence of human ghrelin. Identification of multiple ghrelin-derived molecules produced by post-translational processing."J Biol Chem. 278(1). 64-70 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kaiya H, Kojima M, Hosoda H, Moriyama S, Takahashi A, Kawauchi H, Kangawa K.: "Peptide purification, complementary deoxyribonucleic acid (DNA) and genomic DNA cloning, and functional characterization of ghrelin in rainbow trout."Endocrinology. 144(12). 5215-5226 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kaiya H, Kojima M, Hosoda H, Riley LG, Hirano T, Grau EG, Kangawa K.: "Amidated fish ghrelin : purification, cDNA cloning in the Japanese eel and its biological activity."J Endocrinol. 176(3). 415-423 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakahara K, Hayashida T, Nakazato M, Kojima M, Hosoda H, Kangawa K, Murakami N.: "Effect of chronic treatments with ghrelin on milk secretion in lactating rats."Biochem Biophys Res Commun. 303(3). 751-755 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tanaka K, Minoura H, Isobe T, Yonaha H, Kawato H, Wang DF, Yoshida T, Kojima M, Kangawa K, Toyoda N.: "Ghrelin is involved in the decidualization of human endometrial stromal cells."J Clin Endocrinol Metab. 88(5). 2335-2340 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Kaiya et al.: "Peptide purification, complementary deoxyribonucleic acid (DNA) and genomic DNA cloning, and functional characterization of ghrelin in rainbow trout"Endocrinology. 144. 5215-5226 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Kaiya et al.: "Amidated fish ghrelin : purification, cDNA cloning in the Japanese eel and its biological activity"Journal of Endocrinology. 176. 415-423 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Choi et al.: "The role of ghrelin and growth hormone secretagogues receptor on rat adipogenesis"Endocrinology. 144. 754-759 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Hosoda et al.: "Structural divergence of human ghrelin. Identification of multiple ghrelin-derived molecules produced by post-translational processing"Journal of Biological Chemistry. 278. 64-70 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Nakahara et al.: "Effect of chronic treatments with ghrelin on milk secretion in lactating rats"Biochem.Biophys.Res.Commun.. 303. 751-755 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Tanaka et al.: "Ghrelin is involved in the decidualization of human endometrial stromal cells"J Clin Endocrinol Metab. 88. 2335-2340 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kojima, M., Kangawa K.: "Ghrelin, an orexigenic signaling molecule from the gastrointestinal tract"Curr Opin Pharmacol. 2. 665-668 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Date Y.et al.: "Ghrelin is present in pancreatic alpha-cells of humans and rats and stimulates insulin secretion"Diabetes. 51. 124-129 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kaiya H.et al.: "Chicken ghrelin : purification, cDNA cloning, and biological activity"Endocrinology. 143. 3454-3463 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Murata M.et al.: "Ghrelin modulates the downstream molecules of insulin signaling in hepatoma cells"J Biol. Chem.. 277. 5667-5674 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sugino T.et al.: "A transient ghrelin surge occurs just before feeding in a scheduled meal-fed sheep"Biochem Biophys Res Commun. 295. 255-260 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Murakami N.et al.: "Role for central ghrelin in food intake and secretion profile of stomach ghrelin in rats"J Endocrinol. 174. 283-288 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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