Analysis of the mechanisms of the actions of DIF, a bio-active compound isolated from a soil micro-organism, and development of effective DIF derivatives

• Project/Area Number: 19590136
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Gunma University
• Principal Investigator: KUBOHARA Yuzuru Gunma University, 生体調節研究所, 准教授 (00221937)
• Co-Investigator(Kenkyū-buntansha): KOJIMA Itaru 群馬大学, 生体調節研究所, 教授 (60143492) ; HOSAKA Kohei 群馬大学, 医学部, 教授 (70108992)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 細胞性粘菌 / 分化誘導因子 / がん / 糖尿病 / 肥満 / 抗腫瘍剤 / 糖代謝 / DIF / 低分子化合物

Research Abstract

我々は、細胞性粘菌由来の低分子化合物DIF-1およびその誘導体の薬理活性(抗腫瘍活性と細胞の糖代謝促進活性)を解析し、1) DIF様因子の有する2つの薬理活性は、DIFの側鎖修飾によって分離できる可能性があること、2) DIF-1による糖代謝促進作用は、細胞内のGLUT1を細胞膜に移動させることによって発揮されること、3) DIF-1の誘導体DIF-1(3M)は、KKayマウスの食後の血糖値下降を促進する作用があること等を見出した。

Research Products

• [Journal Article] Novel diterpene pyrone-type compounds, Metarhizin A and B, isolated from entomopathogenic fungus (2009)
  • Author(s): Kikuchi H, Hoshi T, Kitayama M, Sekiya M, Katou Y, Ueda K, Kubohara Y, Sato H, Shimazu M, Kurata S & Oshima Y.
  • Journal Title: Metarhizium flavoviride and their structural requirements for inhibiting cellular proliferation. Tetrahedron 65 Pages: 469-477
  • Peer Reviewed
• [Journal Article] oligosaccharide has suppressive activity against human leukemia cell proliferation (2009)
  • Author(s): Hosomi O, Misawa Y, Takeya AMatahira Y, Sugahara K, Kubohara Y, Yamaura F,& Kudo S. Novel
  • Journal Title: Glycoconjugate J 26 Pages: 189-198
  • Peer Reviewed
• [Journal Article] Novel diterpene pyrone-type compounds, Metarhizin A and B, isolated from entomopathogenic fungus, Metarhizium flavoviride and their struotural requirements for inhibiting cellular proliferation. (2009)
  • Author(s): Kikuchi, H. 他
  • Journal Title: Tetrahedron 65 Pages: 469-477
  • Peer Reviewed
• [Journal Article] Biological activities of novel derivatives of DIF-1 isolated from Dictyostelium (2008)
  • Author(s): Kikuchi H, Ishiko S, Oshima Y, Gonkan N, Hosaka K & Kubohara Y.
  • Journal Title: Biochem.Biophys. Res. Commun 377 Pages: 1012-1017
  • Peer Reviewed
• [Journal Article] Exploitation of the derivatives of Dictyostelium differentiation-inducing factor-1, which promote glucose consumption in mammalian cells (2008)
  • Author(s): Kubohara Y, Kikuchi H & Oshima Y.
  • Journal Title: Life Sciences 83 Pages: 608-612
  • Peer Reviewed
• [Journal Article] Exploitation of the derivatives of Dictyostelium differentiation inducing fact or 1, which promote glucose consumption in mammalian cells. (2008)
  • Author(s): Kubohara, Y. 他
  • Journal Title: Life Sciences 83 Pages: 608-612
  • Peer Reviewed
• [Journal Article] Biological activities of novel derivatives of DIF-1 isolated from Dictyostelium (2008)
  • Author(s): Kikuchi, H. 他
  • Journal Title: Biochem Biophys. Res. Commun. 377 Pages: 1012-1017
  • Peer Reviewed
• [Journal Article] Novel oligosaceharide has suppressive activity against human leukemia cell proliferation. (2008)
  • Author(s): Hosomi, O. 他
  • Journal Title: Glycoconjugate J. 26 Pages: 189-198
  • Peer Reviewed
• [Journal Article] Dihydrodictyopyrone A and C : New members of dictyopyrone family isolated from Dictyostelium cellular slime molds (2007)
  • Author(s): Kikuchi H, Nakamura K, Kubohara Y, Gokan N, Hosaka K, Maeda Y, & Oshima Y.
  • Journal Title: Tetrahedron Lett 48 Pages: 5905-5909
  • Peer Reviewed
• [Journal Article] Dictyostelium differentiation-inducing factor-1 induces glucose transporter 1 translocation and promotes glucose uptake in mammalian cells (2007)
  • Author(s): Omata W, Shibata H, Nagasawa M,Kojima I, Kikuchi H, Oshima Y, Hosaka K,& Kubohara Y
  • Journal Title: FEBS Journal 274 Pages: 3392-3404
  • Peer Reviewed
• [Journal Article] 細胞性粘菌由来の薬理活性物質DIF-1が示す抗腫瘍作用と糖代謝促進作用 (2007)
  • Author(s): 久保原禅
  • Journal Title: 細胞工学 26 Pages: 1052-1053
• [Journal Article] Dictyostelium differentiation-inducing factor-1 induces glucose transporter 1 translocation and promotes glucose uptake in mammalian cells (2007)
  • Author(s): Omata, W., 他
  • Journal Title: FEBS Journa1 274 Pages: 3392-3404
  • Peer Reviewed
• [Journal Article] Dihydrodictyopyrone A and C:New members of dictyopyrone family isolated from Dictyostelium cellular shme molds (2007)
  • Author(s): Kikuchi, H., 他
  • Journal Title: Tetrahedron Letters 48 Pages: 5905-5909
  • Peer Reviewed
• [Journal Article] 細胞性粘菌由来の薬理活性物質DIF-1が示す抗腫瘍作用と糖代謝促進作用 (2007)
  • Author(s): 久保原 禅
  • Journal Title: 細胞工学 26 Pages: 1052-1053
• [Presentation] Biologically active small molecules produced by cellular slime molds (2008)
  • Author(s): Kikuchi H, Ishiko S, Amagai A, Maeda Y Hosaka H, Kuboahra Y,& Oshima Y.
  • Organizer: International Dictyostelium conference
  • Place of Presentation: Tsukuba
  • Year and Date: 2008-09-16
• [Presentation] Biological activities of DIF-1 derivatives (2008)
  • Author(s): Kubohara Y, Kikuchi H,& Oshima Y.
  • Organizer: International Dictyostelium conference
  • Place of Presentation: Tsukuba
  • Year and Date: 2008-09-16
• [Presentation] Biological activities of DIF-1 derivatives. (2008)
  • Author(s): Kubohara, Y. 他
  • Organizer: International Dictyostelium conference
  • Place of Presentation: 筑波
  • Year and Date: 2008-09-16
• [Presentation] Biologically active small molecules produced by cellular slime molds (2008)
  • Author(s): Kikuchi, H. 他
  • Organizer: International Dictyostelium conference
  • Place of Presentation: 筑波
  • Year and Date: 2008-09-16
• [Presentation] 胚性癌腫細胞(P19.CL6)の心筋細胞への分化におけるBr-DIF-1の役割 (2008)
  • Author(s): 瀬谷和彦、(他9名)、久保原禅、古川賢一
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-27
• [Presentation] (2007)
  • Author(s): 久保原禅
  • Organizer: 第10回細胞性粘菌研究会
  • Place of Presentation: 弘前
  • Year and Date: 2007-11-04
• [Presentation] 哺乳類細胞に対するDIF-1およびその誘導体の糖代謝促進作用 (2007)
  • Author(s): 久保原禅、小俣和香、柴田宏、小島至、保坂公平、菊地晴久, 大島吉輝
  • Organizer: 第10回細胞性粘菌研究会
  • Place of Presentation: 弘前
  • Year and Date: 2007-11-04
• [Presentation] 哺乳類細胞に対するDIF-1の薬理作用 (2007)
  • Author(s): 久保原 禅
  • Organizer: 第10回細胞性粘菌研究会
  • Place of Presentation: 弘前
  • Year and Date: 2007-11-04
• [Presentation] 哺乳類細胞に対するDIF-1の糖代謝促進作用 (2007)
  • Author(s): 久保原禅、小俣和香、柴田宏、小島至、保坂公平、菊地晴久, 大島吉輝
  • Organizer: 第10回細胞性粘菌研究会
  • Place of Presentation: 弘前
  • Year and Date: 2007-11-03
• [Presentation] Anti-leukemic activities of Dictyostelium secondary metabolites : A novel aromatic metabolite, 4-methyl-5- n-pentylbenzene-1,3-diol, isolated from Dictyostelium mucoroides suppresses cell growth in human leukemia K562 and HL-60 cells (2007)
  • Author(s): 久保原禅、後閑直美、保坂公平、菊地晴久、大島吉輝
  • Organizer: 細胞生物・発生生物合同学会
  • Place of Presentation: 福岡
  • Year and Date: 2007-05-30
• [Presentation] Anti-leukemic activities of Dictyostelium secondary metabolites:A novel aromatic metabolite,4-methyl-5-n-pentylbenzene-1,3-diol,isolated from Dictyostelium mucoroides suppresses cell growth in human leukemia K562 and HL-60 cells. (2007)
  • Author(s): 久保原 禅, 他
  • Organizer: 細胞生物学会・発生生物学会合同学会
  • Place of Presentation: 福岡
  • Year and Date: 2007-05-30
• [Book] 群馬に多い病気~生活習慣病を知り、克服する (2007)
  • Author(s): 小島至、久保原禅(他7名)、ブックレット群馬大学1
  • Total Pages: 72
  • Publisher: 上毛新聞社刊
• [Book] 群馬に多い病気〜生活習慣病を知り、克服する (2007)
  • Author(s): 小島 至, 他
  • Total Pages: 72
  • Publisher: 上毛新聞出版局
• [Remarks]
  • URL: http://www.imcr.gunma-u.ac.jp/lab/molgen/index.html
• [Remarks] 所属研究室HP
  • URL: http://imcr.showa.gunma-u.ac.jp/lab/genetics/index.html
• [Remarks] 所属研究室HP:
  • URL: http://imcr.showa.gunma-u.ac.jp/lab/genetics/index.html
• [Patent(Industrial Property Rights)] 新規DIF-1誘導体 (2009)
  • Inventor(s): 久保原禅
  • Industrial Property Rights Holder: 群馬大学
  • Filing Date: 2009-02-05
• [Patent(Industrial Property Rights)] 新規DIF-1誘導体 (2009)
  • Inventor(s): 久保原禅
  • Industrial Property Rights Holder: 群馬大学
  • Industrial Property Number: 2009-025149
  • Filing Date: 2009-02-05
• [Patent(Industrial Property Rights)] Method of lowering blood glucose and method of preventing or treating blood glucose and method of preventing or treating diabetes and obesity (2007)
  • Inventor(s): 久保原禅、柴田宏
  • Industrial Property Rights Holder: 群馬大学
  • Filing Date: 2007-10-24
• [Patent(Industrial Property Rights)] Method of lowering blood glucose and method of preventing or treating bolld glucose and method of preventing or treating diabetes and obesity (2007)
  • Inventor(s): 久保原 禅, 柴田 宏
  • Industrial Property Rights Holder: 群馬大学
  • Filing Date: 2007-10-24
  • Overseas