Regulation of mTOR-mediated nutrition sensing system

• Project/Area Number: 19590308
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kobe University
• Principal Investigator: HARA Kenta Kobe University, 大学院医学研究科, 助教 (70397826)
• Co-Investigator(Kenkyū-buntansha): YOKONO Koichi 神戸大学, 大学院医学研究科, 教授 (50144580) ; NAGATA Masao 神戸大学, 大学院医学研究科, 准教授 (70294220) ; MORIYAMA Hiroaki 神戸大学, 大学院医学研究科, 臨床研究員 (70372646) ; YASUDA Hisafumi 神戸大学, 大学院医学研究科, 臨床研究員 (50403233)
• 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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 分子病態栄養学 / 栄養センサー / mTOR / 細胞内シグナル

Research Abstract

1.mTORを介した細胞内シグナルの分子基盤の解明:Raptorに結合する新規蛋白としてPRAS40を見出した。PRAS40はmTORによって直接しリン酸化される生理的基質であることが判明した。
2.mTORシグナル改変モデルマウスの解析:膵β細胞特異的にmTORC1経路が活性化されたマウスを作製し解析した。このマウスは良好なインスリン分泌能を示し、膵β細胞の破壊や肥満によって引きおこされる糖尿病の発症を抑制していた。

Research Products

• [Journal Article] Upregulation of the mTOR Complex 1 Pathway by Rheb in Pancreatic β Cells Leads to Increased β Cell Mass and Prevention of Hyperglycemia. (2009)
  • Author(s): Hamada S., Hara K., Hamada T., Yasuda H., Moriyama H., Nakayama R., Nagata M., Yokono K.
  • Journal Title: Diabetes. 58 Pages: 1321-1332
  • Peer Reviewed
• [Journal Article] One amino acid difference is critical for suppression for the development of experimental autoimmune diabetes (EAD) with intravenous injection of insulin:9-23 peptide. (2008)
  • Author(s): Okumachi Y., Moriyama H., Kameno M., Arai T., Kishi Okumachi Y., Moriyama H., Kameno M., Arai T., Kishi M., Kurohara M., Yamada K., Yasuda H., Hara K., Yokono K. Nagata M.
  • Journal Title: Biochem. Biophys. Res. Commun. 374 Pages: 581-586
  • Peer Reviewed
• [Journal Article] Prevention of recurrent but not spontaneous autoimmune diabetes by transplanted NOD islets adenovirally transduced with immunomodulationg molecules. (2008)
  • Author(s): Sakata M., Yasuda H., Moriyama K., Yamada K., Kotani R., Kurohara M., Okumachi Y., Kishi M., Arai T., Hara K., Hamada H., Yokono K., Nagata M.
  • Journal Title: Diabetes Res.Clin.Pract. 80 Pages: 352-359
  • Peer Reviewed
• [Journal Article] Prevention of recurrent but not spontaneous auloimmune diabetes by transplanted NOD islets adcnovirally transduced with immunomodulationg molecules. (2008)
  • Author(s): Sakata M., et al.
  • Journal Title: Diabetes Res. Clin. Pract. 80 Pages: 352-359
  • Peer Reviewed
• [Journal Article] One amino acid difference is critical for suppression for the devclopmenl of experimental autoimmune diabetes (KAD) with intravenous injection of insulin : 9-23 peptide. (2008)
  • Author(s): Okumachi Y.
  • Journal Title: Biochem. Biopkys. Res. Commun. 374 Pages: 581-586
  • Peer Reviewed
• [Journal Article] Regulation of hypoxia-inducible factor 1 by glucose availability under hypoxic conditions. (2008)
  • Author(s): Zhou J.,
  • Journal Title: Kobe J. Med. Sci. (In press)
  • Peer Reviewed
• [Journal Article] The Proline-Rich Akt Substrate of 40 kDa (PRAS40) is a physiological substrate of mTOR complex 1 (2007)
  • Author(s): Oshiro N., Takahashi R., Yoshino K-I., Tanimura K., Nakashima A., Eguchi S., Miyamoto T., Hara K., Takehana K., Avruch J., Kikkawa U., Yonezawa K.
  • Journal Title: J. Biol. Chem 282 Pages: 20329-20339
  • Peer Reviewed
• [Journal Article] Regulation of hypoxia-inducible factor 1 by glucose availability under hypoxic conditions. (2007)
  • Author(s): Zhou J., Hara K., Inoue M., Hamada S., Yasuda H., Moriyama H., Endo H., Hirota K., Yonezawa K., Nagata M., Yokono K.
  • Journal Title: Kobe J. Med. Sci 53 Pages: 283-296
  • NAID: 110006646896
  • Peer Reviewed
• [Journal Article] Modification of the Rb-binding Domain of Replication- Competent Adenovirus Vector Enhances Cytotoxicity Against Human Esophageal Cancers via NF-kB Activity. (2007)
  • Author(s): Yamada K., Moriyama H., Yasuda H., Hara K., Maniwa Y., Hamada H., Yokono K., Nagata M.
  • Journal Title: Human Gene Therapy 2007 18 Pages: 389-400
  • Peer Reviewed
• [Journal Article] Insulin as a T cell antigen in type 1 diabetes supported by the evidence from the insulin knouckout NOD mice. (2007)
  • Author(s): Moriyama H., Nagata M., Arai T., Okumachi Y., Yamada K., Kotani R., Yasuda H., Hara K., Yokono K.
  • Journal Title: Diabetes Res.Clin.Pract. 77
  • Peer Reviewed
• [Journal Article] Immunological Aspects of 'Fulminant Type 1 Diabetes' (2007)
  • Author(s): Nagata M.
  • Journal Title: Diabetes Res. Clin. Pract. 77 Pages: 99-103
• [Journal Article] Insulin as a T cell antigen in type 1 diabetes supported by the evidence from the insulin knouckout NOD mice. (2007)
  • Author(s): Moriyama H.
  • Journal Title: Diabetes Res. Clin. Pract. 77 Pages: 155-160
• [Journal Article] The Proline-Rich Akt Substrate of 40 kDa(PRAS40)is a physiological substrate of mTOR complex 1. (2007)
  • Author(s): Oshiro N.
  • Journal Title: J. Biol. Chem. 282 Pages: 20329-20339
  • Peer Reviewed
• [Journal Article] Modification of the Rb-binding Domain of Replication-Competent Adenovirus Vector Enhances Cytotoxicity Against Human Esophageal Cancers via NF-kB Activity. (2007)
  • Author(s): Yamada K.
  • Journal Title: Human Gene Therapy 18 Pages: 389-400
  • Peer Reviewed
• [Journal Article] Immunological Aspects of 'Fulminant Type 1 Diabetes.
  • Author(s): Nagata M., Moriyama H., Kotani R., Yasuda H., Kishi M., Kurohara M., Hara K., Yokono K.
  • Journal Title: Diabetes Res. Clin. Pract. Pages: 0-0
  • Peer Reviewed
• [Journal Article] Upregulalion of the mTOR Complex 1 pathway by Rheb in pancreatic β cells leads to increased β cell mass and prevention of hyperglycemia.
  • Author(s): Hamada s.
  • Journal Title: Diabetes (In press)(掲載確定)
  • Peer Reviewed
• [Presentation] Upregulatjon of the mTOR Complex 1 pathway by Rheb in pancrcalic β cells leads to increased β cell mass and prevention of hyperglycemia. (2008)
  • Author(s): 原 賢太
  • Organizer: Scientific Sessions, American Diabetes Association
  • Place of Presentation: アメリカ合衆国サンフランシスコ
  • Year and Date: 2008-06-06
• [Presentation] 膵β細胞におけるmTORシグナルの活性化と糖尿病発症の抑制 (2008)
  • Author(s): 濱田水鈴、原 賢太、中村 晃、安田尚史、森山啓明、永田正男、横野浩一
  • Organizer: 第50回日本老年医学会学術集会・総会
  • Place of Presentation: 千葉
• [Presentation] Upregulation of mTORC1 pathway by Rheb in pancreatic βcells leads to increased β cell mass and prevention of hyperglycemia. 68th Scientific Sessions (2008)
  • Author(s): Kenta Hara, Suirin Hamada, Akira Nakamura, Hisafumi Yasuda, Hiroaki Moriyama, Masao Nagata, Koichi Yokono
  • Organizer: The American Diabetes Association
  • Place of Presentation: San Francisco, CA, USA
• [Presentation] mTORシグナルのRhebによる活性化は膵β細胞の成長を促し高血糖を抑制する (2008)
  • Author(s): 濱田水鈴、原 賢太、中村 晃、安田尚史、森山啓明、永田正男、横野浩一
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
• [Presentation] RhebによるmTORC1経路の活性化は膵β細胞の成長を促し高血糖を抑制する (2007)
  • Author(s): 原 賢太、濱田水鈴、濱田 猛、中村 晃、安田尚史、森山啓明、永田正男、横野浩一
  • Organizer: 第19回分子糖尿病学シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2007-12-08
• [Presentation] RhebによるmTORC1経路の活性化は膵β細胞の成長を促し高血糖を抑制する。 (2007)
  • Author(s): 原 賢太
  • Organizer: 第19回分子糖尿病シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2007-12-08
• [Presentation] 肥満糖尿病モデルマウスKK-AyマウスにおけるmTOR遺伝子ヘテロ欠損は肥満抵抗性をもたらす。 (2007)
  • Author(s): 原 賢太
  • Organizer: 第50回日本糖尿病学会年次学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2007-05-25
• [Book] 糖尿病学 基礎と臨床「インスリンによる蛋白合成系とその調節」 (2007)
  • Author(s): 原賢太、米澤一仁
  • Publisher: 西村書店