The role of TORC signal on impaired glucose tolerance and cloning the new protein binding with TORC.

• Project/Area Number: 20591050
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The University of Tokyo
• Principal Investigator: SAKODA Hideyuki The University of Tokyo, 医学部附属病院, 助教 (50376464)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: エネルギー / 糖質代謝異常 / インスリンシグナル伝達系 / 糖尿病 / インスリン抵抗性

Research Abstract

Excess nutrient intake leads to activation of mTORC1 and mTORC1 inhibits insulin signal transduction, such that activation of mTOR signaling may lead to insulin resistance and even diabetes mellitus. In the case of insulin action, mTORC1 and mTORC2 have contradictory effects on insulin signaling. Conversely, mTOR also activates Akt, a key molecule in the actions of insulin. Thus, we consider it essential to perform these studies focusing on alterations in the total LST8 amount as well as changes in mTORC1 and mTORC2 to elucidate the pathogenesis of various disorders including cancer and the metabolic syndrome.

Research Products

• [Journal Article] mTORシグナルと糖脂質代謝異常 (2011)
  • Author(s): 迫田秀之, 浅野知一郎
  • Journal Title: 実験医学 29(6) Pages: 895-899
• [Journal Article] Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 associates with IRS-1 and enhances insulin actions and adipogenesis. (2011)
  • Author(s): Nakatsu Y, Sakoda H, Kushiyama A, Zhang J, Ono H, Fujishiro M, Kikuchi T, Fukushima T, Yoneda M, Ohno H, Horike N, Kanna M, Tsuchiya Y, Kamata H, Nishimura F, Isobe T, Ogihara T, Katagiri H, Oka Y, Takahashi SI, Kurihara H, Uchida T, Asano T.
  • Journal Title: J Biol Chem 286(23) Pages: 20812-22
  • Peer Reviewed
• [Journal Article] 4F2hc stabilizes GLUT1 protein and increases glucose transport activity. (2011)
  • Author(s): Ohno H, Nakatsu Y, Sakoda H, Kushiyama A, Ono H, Fujishiro M, Otani Y, Okubo H, Yoneda M, Fukushima T, Kamata H, Nishimura F, Kurihara H, Katagiri H, Oka Y, Asano T.
  • Journal Title: Am J Physiol Cell Physiol 300(5)
  • Peer Reviewed
• [Journal Article] 4F2hc stabilizes GLUT1 protein and increases glucose transport activity. (2011)
  • Author(s): Ohno H, sakoda h, et.al
  • Journal Title: Am J Physiol Cell Physiol. Volume: (掲載確定,印刷中 掲載確定)
  • Peer Reviewed
• [Journal Article] Association between Type 1 Diabetes Mellitus and Remitting Seronegative Symmetrical Synovitis with Pitting Edema: A case report. (2010)
  • Author(s): Sakoda H, Ito S, Kanda H, Fujishiro M, Osuga J, Tsukamoto K, Ueki K, Kadowaki T.
  • Journal Title: Diabetes Res Clin Pract. 91(2)
  • Peer Reviewed
• [Journal Article] Pin1 associates with and induces translocation of CRTC2 to the cytosol, thereby suppressing CRE transcriptional activity. (2010)
  • Author(s): Nakatsu Y, Sakoda H, Kushiyama A, Ono H, Fujishiro M, Horike N, Yoneda M, Ohno H, Kamata H, Tahara H, Isobe T, Nishimura F, Katagiri H, Oka Y, Fukushima T, Takahashi SI, Kurihara H, Uchida T, Asano T.
  • Journal Title: J Biol Chem. 285(43) Pages: 33018-27
  • Peer Reviewed
• [Journal Article] Paraquat-induced oxidative stress represses PI 3-kinase activities leading to impaired glucose uptake in 3T3-L1 adipocytes. (2010)
  • Author(s): Shibata M.; Hakuno F.; Yamanaka D.; Okajima H.; Fukushima T.; Hasegawa T.; Ogata T.; Toyoshima Y.; Chida K.; Kimura K.; Sakoda H.; Takenaka A.; Asano,T ; Takahashi S.I.
  • Journal Title: J Biol Chem. 285(27) Pages: 20915-25
  • Peer Reviewed
• [Journal Article] Macrophage foam cell formation is augmented in serum from patients with diabetic angiopathy. (2010)
  • Author(s): Cui X, Kushiyama A, Yoneda M, Nakatsu Y, Guo Y, Zhang J, Ono H, Kanna M, Sakoda H, Ono H, Kikuchi T, Fujishiro M, Shiomi M, Kamata H, Kurihara H, Kikuchi M, Kawazu S, Nishimura F, Asano T.
  • Journal Title: Diabetes Res Clin Pract. 87(1) Pages: 57-63
  • Peer Reviewed
• [Journal Article] Decreased SIRT1 expression and LKB1 phosphorylation occurs with long-term high-fat diet feeding, in addition to AMPK phosphorylation impairment in the early phase. (2010)
  • Author(s): Yoneda M, Guo Y, Ono H, Nakatsu Y, Zhang Y, Cui X, Iwashita M, Kumamoto S, Tsuchiya Y, Sakoda H, Fujishiro M, Kushiyama A, Koketsu Y, Kikuchi T, Kamata H, Nishimura F, Asano T.
  • Journal Title: Obesity Res Clin Pract 4.
  • Peer Reviewed
• [Journal Article] Paraquat-induced oxidative stress represses PI 3-kinase activities leading to impaired glucose uptake in 3T3-L1 adipocytes (2010)
  • Author(s): Shibata M, sakoda h, et.al
  • Journal Title: J.Biol.Chem. Volume: 285(27) Pages: 20915-20925
  • Peer Reviewed
• [Journal Article] Pin1 associates with and induces translocation of CRT C2 to the cytosol, thereby suppressing CRE transcriptional activity (2010)
  • Author(s): Nakatsu Y, sakoda h, et.al
  • Journal Title: J Biol Chem Volume: 285(43) Pages: 33018-33027
  • Peer Reviewed
• [Journal Article] Macrophage foam cell formation is augmented in serum from patients with diabetic angiopathy. (2010)
  • Author(s): Cui X, sakoda h, et.al.
  • Journal Title: Diabetes Res Clin Pract 87(1) Pages: 57-63
  • Peer Reviewed
• [Journal Article] Growth Hormone Inhibition of Glucose Uptake in Adipocytes Occurs without Affecting GLUT4 Translocation through an Insulin Receptor Substrate-2-Phosphatidylinositol 3-Kinase-dependent Pathway. (2009)
  • Author(s): Sasaki-Suzuki N, Arai K, Ogata T, Kasahara K, Sakoda H, Chida K, Asano T, Pessin JE, Hakuno F, Takahashi S.
  • Journal Title: J Biol Chem. 284(10) Pages: 6061-70
  • Peer Reviewed
• [Journal Article] Long-term Forskolin Stimulation Induces AMPK Activation and Thereby Enhances Tight Junction Formation in Human Placental Trophoblast BeWo Cells. (2008)
  • Author(s): Egawa M, Kudo Y, Kamata H, Kushiyama A, Sakoda H, Fujishiro M, Horike N, Yoneda M, Nakatsu Y, Ying G, Jun Z, Tsuchiya Y, Takata K, Kurihara H, Asano T.
  • Journal Title: Placenta. 29(12) Pages: 1003-8
  • Peer Reviewed
• [Journal Article] AMPK activation increases phosphorylation of GSK3beta and thereby reduces CRE transcriptional activity and PEPCK-C gene expression in the liver. (2008)
  • Author(s): Horike N, Sakoda H, Kushiyama A, Ono H, Fujishiro M, Kamata H, Nishiyama K, Uchijima Y, Kurihara Y, Kurihara H, Asano T.
  • Journal Title: J Biol Chem. 283(49) Pages: 33902-10
  • Peer Reviewed
• [Journal Article] Activation of hypothalamic S6 kinase mediates diet-induced hepatic insulin resistance in rats. (2008)
  • Author(s): Ono H, Pocai A, Wang Y, Sakoda H, Asano T, Backer JM, Schwartz GJ, Rossetti L.
  • Journal Title: J Clin Invest. 118(8) Pages: 2959-68
  • Peer Reviewed
• [Journal Article] Hepatic overexpression of a dominant negative form of raptor enhances Akt phosphorylation and restores insulin sensitivity in K/KAy mice. (2008)
  • Author(s): Koketsu Y, Sakoda H, Fujishiro M, Kushiyama A, Fukushima Y, Ono H, Anai M, Kikuchi T, Fukuda T, Kamata H, Horike N, Uchijima Y, Kurihara H, Asano T.
  • Journal Title: Am J Physiol Endocrinol Metab. 294(4)
  • Peer Reviewed
• [Journal Article] Activation of hypothalamic S6 kinase mediates diet-induced hepatic insulin resistance in rats. (2008)
  • Author(s): Ono H
  • Journal Title: J Clin Invest. 118(8) Pages: 2959-68
  • Peer Reviewed
• [Journal Article] Hepatic overexpression of a dominant negative form of raptor enhances Akt phosphorylation and restores insulin sensitivity in K/KAy mice. (2008)
  • Author(s): Koketsu Y
  • Journal Title: Am J Physiol Endocrinol Metab. 294(4)
  • Peer Reviewed
• [Presentation] LST8 level controls basal p70 S6 kinase and Akt phosphorylations, and mTORC1 and mTORC2 negatively regulate each other by competing for association with LST8 (2010)
  • Author(s): Kikuchi T, Sakoda H, et al.
  • Organizer: 第70回アメリカ糖尿病学会学術集会
  • Place of Presentation: Orland, USA
• [Presentation] LST8によるmTORおよびインスリンシグナルのAktリン酸化への関与 (2010)
  • Author(s): 菊池貴子、迫田秀之、etc.
  • Organizer: 日本糖尿病学会学術集会
  • Place of Presentation: 岡山
• [Presentation] Impaired mTORc1 Stability Results in LST8 Transfer to mTORc2 and the Enhancement of Akt Phosphorylation in HepG2 Cells (2009)
  • Author(s): 菊池貴子, 迫田秀之, et al.
  • Organizer: 第69回アメリカ糖尿病学会学術集会
  • Place of Presentation: New Orleans, USA
• [Presentation] mTORシグナルのAktリン酸化への関与 (2009)
  • Author(s): 菊池貴子、迫田秀之, etc.
  • Organizer: 日本糖尿病学会学術集会
  • Place of Presentation: 大阪
• [Presentation] Impaired mTORc1 Stability Results in LST8 Transfer to mTORc2 and the Enhancement of Akt Phosphorylation in HeuG2 Cells (2009)
  • Author(s): TAKAKO KIKUCHI
  • Organizer: American Diabetes Association 69^<th> Scientific Sessions.
  • Place of Presentation: New Orleans USA
• [Presentation] Enhancement of Akt phosphorylation in HepG2 by overexpressing C terminally deleted Raptor (2008)
  • Author(s): 菊池貴子, 迫田秀之, et al.
  • Organizer: 第68回アメリカ糖尿病学会学術集会
  • Place of Presentation: San Francisco, USA
• [Presentation] mTORシグナルによるAktリン酸化調整機序の解明 (2008)
  • Author(s): 菊池貴子、迫田秀之, etc.
  • Organizer: 日本糖尿病学会学術集会
  • Place of Presentation: 東京
• [Presentation] 細胞内エネルギー状態とインスリンシグナル伝達系の関連 (2008)
  • Author(s): 福田武俊、迫田秀之、etc.
  • Organizer: 日本糖尿病学会学術集会
  • Place of Presentation: 東京
• [Presentation] Enhancement of Akt Phosphoryolation in HepG2 by Overexpressing C Terminally Deleted Raptor (2008)
  • Author(s): Kikuchi T
  • Organizer: American Diabetes Association 68th Scientific Sessions.
  • Place of Presentation: San Francisco, USA