Roles of trk-fused gene product protein

• Project/Area Number: 26670451
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Hiroshima University
• Principal Investigator: Asano Tomoichiro 広島大学, 医歯薬保健学研究院(医), 教授 (70242063)
• Co-Investigator(Renkei-kenkyūsha): NAKATSU YUSUKE 広島大学, 大学院医歯薬保健学研究院, 講師 (20452584) ; FUKUSHIMA TOSHIAKI 広島大学, 大学院医歯薬保健学研究院, 助教 (70543552) ; SAKODA HIDEYUKI 宮崎大学, 医学部附属病院, 講師 (50376464) ; FUJISHIRO MIDORI 東京大学, 医学部附属病院, 助教 (50420211) ; HONDA HIROAKI 広島大学, 原爆放射線医科学研究所, 教授 (40245064)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 代謝 / 糖尿病 / ＴＦＧ / インスリン / 糖・脂質代謝 / TFG

Outline of Final Research Achievements

We identified TFG asa a protein which binds to PTEN. In fact, overexpression of TFG in the cultured cells induced an increased intracellular content of PIP3. In addition, recent reports revealed the TFG gene to be responsible for the occurence of nerurogenerative diseases. Thus, we generated tissue- specific TFG KO mice, to elucidate the roles of TFG on metabolic as well as neural functions. We found the reduced mass of pancreatic beta cells and impaired glucose-induced insulin secretion in the beta cell specific TFG KO mice. Therefore, TFG plays a critical role on not only the neural function, but also glucose metabolism via the regulation of insulin secretion. At present, we are trying to reveal the detailed machanisms underlying TFG-induced regulation of insulin secretion.

Research Products

• [Journal Article] Treatment with the SGLT2 inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mellitus. (2015)
  • Author(s): Qiang, S., Nakatsu, Y., Seno, Y., Fujishiro, M., Sakoda, H., Kushiyama, A., Mori, K., Matsunaga, Y., Yamamotoya, T., Kamata, H., and Asano, T.
  • Journal Title: Diabetol. Metab. Syndr. Volume: 7 Pages: 104-104
  • Peer Reviewed
• [Journal Article] Prolyl Isomerase Pin1 Negatively Regulates AMPK by Associating with the CBS Domain in the γ-subunit. (2015)
  • Author(s): Nakatsu, Y., Iwashita, M., Sakoda, H., Ono, H., Nagata, K., Matsunaga, Y., Fukushima, T., Fujishiro, M., Kushiyama, A., Kamata, H., Takahashi, S., Katagiri, H., Honda, H., Kiyonari, H., Uchida, T., and Asano, T.
  • Journal Title: J. Biol. Chem. Volume: 290 Pages: 24255-24266
  • Peer Reviewed
• [Journal Article] A hepatic amino acid/mTOR/S6K-dependent signalling pathway modulates systemic lipid metabolism via neuronal signals. (2015)
  • Author(s): Uno, K., Yamada, T., Ishigaki, Y., Imai, J., Hasegawa, Y., Sawada, S., Kaneko, K., Ono, H., Asano, T., Oka, Y., and Katagiri, H.
  • Journal Title: Nat. Commun. Volume: 6 Pages: 7940-7940
  • Peer Reviewed
• [Journal Article] Distinct Time Course of the Decrease in Hepatic AMP-Activated Protein Kinase and Akt Phosphorylation in Mice Fed a High Fat Diet. (2015)
  • Author(s): Shiwa, M., Yoneda, M., Okubo, H., Ohno, H., Kobuke, K., Monzen, Y., Kishimoto, R., Nakatasu, Y., Asano, T., and Kohno, N.
  • Journal Title: PLoS One Volume: 10
  • Peer Reviewed
• [Journal Article] LUBAC Formation Is Impaired in the Livers of Mice with MCD-Dependent Nonalcoholic Steatohepatitis. (2015)
  • Author(s): Matsunaga, Y., Nakatsu, Y., Fukushima, T., Okubo, H., Iwashita, M., Sakoda, H., Fujishiro, M., Yamamotoya, T., Kushiyama, A., Takahashi, S., Tsuchiya, Y., Kamata, H., Tokunaga, F., Iwai, K., and Asano, T.
  • Journal Title: Mediators Inflamm. Volume: 12 Pages: 125380-125380
  • NAID: 120005745641
  • Peer Reviewed
• [Journal Article] High-fat diet feeding significantly attenuates anagliptin-induced regeneration of islets of Langerhans in streptozotocin-induced diabetic mice. (2015)
  • Author(s): Shinjo, T., Nakatsu, Y., Iwashita, M., Sano, T., Sakoda, H., Ishihara, H., Kushiyama, A., Fujishiro, M., Nishimura, F., and Asano, T.
  • Journal Title: Diabetol. Metab. Syndr. Volume: 7 Pages: 50-50
  • Peer Reviewed
• [Journal Article] Protection from diet-induced obesity and insulin resistance in mice lacking CCL19-CCR7 signaling. (2015)
  • Author(s): Sano, T., Iwashita, M., Nagayasu, S., Yamashita, A., Shinjo, T., Hashikata, A., Asano, T., Kushiyama, A., Ishimaru, N., Takahama, Y., and Nishimura, F.
  • Journal Title: Obesity Volume: 23 Pages: 1460-1471
  • Peer Reviewed
• [Journal Article] Pin1 Inhibitor Juglone Exerts Anti-Oncogenic Effects on LNCaP and DU145 Cells despite the Patterns of Gene Regulation by Pin1 Differing between These Cell Lines. (2015)
  • Author(s): Kanaoka, R., Kushiyama, A., Seno, Y., Nakatsu, Y., Matsunaga, Y., Fukushima, T., Tsuchiya, Y., Sakoda, H., Fujishiro, M., Yamamotoya, T., Kamata, H., Matsubara, A., and Asano, T.
  • Journal Title: PLoS One. Volume: 10
  • Peer Reviewed
• [Journal Article] DPP-IV inhibitor anagliptin exerts anti-inflammatory effects on macrophages, adipocytes, and mouse livers by suppressing NF-κB activation. (2015)
  • Author(s): Shinjo, T., Nakatsu, Y., Iwashita, M., Sano, T., Sakoda, H., Ishihara, H., Kushiyama, A., Fujishiro, M., Fukushima, T., Tsuchiya, Y., Kamata, H., Nishimutra, F., and Asano, T.
  • Journal Title: Am. J. Physiol. Endocrinol Metab. Volume: 309
  • Peer Reviewed
• [Journal Article] The xanthine oxidase inhibitor febuxostat suppresses development of nonalcoholic steatohepatitis in a rodent model. (2015)
  • Author(s): Nakatsu, Y., Seno, Y., Kushiyama, A., Sakoda, H., Fujishiro, M., Katasako, A., Mori, K., Matsunaga, Y., Fukushima, T., Kanaoka, R., Yamamotoya, T., Kamata, H., and Asano, T.
  • Journal Title: Am. J. Physiol. Gastrointest Liver Physiol. Volume: 308
  • Peer Reviewed
• [Journal Article] Nedd4-induced monoubiquitination of IRS-2 enhances IGF signalling and mitogenic activity (2015)
  • Author(s): Fukushima, T., Yoshihara, H., furuta, H., Kamei, H., Hakuno, F., Luan, J., Duan, C., Saeki, Y., Tanaka, K., Iemura, S., Natsume, T., Chida, K., Nakatsu, Y., Kamata, H., Asano, T., and Takahashi, S.
  • Journal Title: Nat. Commun. Volume: 6 Pages: 6780-6780
  • NAID: 120006348510
  • Peer Reviewed
• [Journal Article] Mosapride citrate improves nonalcoholic steatohepatitis with increased fecal lactic acid bacteria and plasma glucagon-like peptide-1 level in a rodent model. (2015)
  • Author(s): Okubo, H., Nakatsu, Y., Sakoda, H., Kushiyama, A., Fujishiro, M., Fukushima, T., Matsunaga, Y., Ohno, H., Yoneda, M., Kamata, H., Shinjo, T., Iwashita, M., Nishimura, F., and Asano, T.
  • Journal Title: Am. J. Physiol. Gastrointest Liver Physiol. Volume: 308
  • Peer Reviewed
• [Journal Article] Insulin receptor substrate-4 binds to Slingshot-1 phosphatase and promotes cofilin dephosphorylation. (2014)
  • Author(s): Homma, Y., Kanno, S., Sasaki, K., Nishita, M., Yasui, A., Asano, T., Ohashi, K., and Mizuno, K.
  • Journal Title: J. Biol. Chem. Volume: 289 Pages: 26302-13
  • Peer Reviewed
• [Journal Article] A high-throughput screen for inhibitors of the prolyl isomerase, Pin1, identifies a seaweed polyphenol that reduces adipose cell differentiation. (2014)
  • Author(s): Mori, T., Hidaka, M., Ikuji, H., Yoshizawa, I., Toyohara, H., Okuda, T., Uvhida, C., Asano, T., Yotsu-Yamashita, M., and Uchida, T.
  • Journal Title: Biosci. Biotechnol. Biochem Volume: 78 Pages: 832-8
  • Peer Reviewed
• [Journal Article] Mediobasal hypothalamic PTEN modulates hepatic insulin resistance independently of food intake in rats. (2014)
  • Author(s): Sumita, T., Ono, H., Suzuki, T., Inukai, K., Katagiri, H., Asano, T., Katayama, S., and Awata, T.
  • Journal Title: Am. J. Physiol. Endocrinol Metab. Volume: 307
  • Peer Reviewed
• [Journal Article] Insulin receptor substrate-1 associates with small nucleolar RNA which contributes to ribosome biogenesis. (2014)
  • Author(s): Ozoe, A., Sone, M., Fukushima, T., Kataoka, N., Chida, K., Asano, T., Hakuno, F., and Takahashi, S.
  • Journal Title: Front Endocrinol. Volume: 5 Pages: 1-12
  • Peer Reviewed
• [Journal Article] The inflammation-lipocalin 2 axis may contribute to the development of chronic kidney disease. (2014)
  • Author(s): Hashikata, A., Yamashita, A., Suzuki, S., Nagayasu, S., Shinjo, T., Taniguchi, A., Fukushima, M., Nakai, Y., Nin, K., Watanabe, N., Asano, T., Abiko, Y., Kushiyama, A., Nagasaka, S.,and Nishimura, F.
  • Journal Title: Nephrol. Dial. Transplant. Volume: 29 Pages: 611-8
  • Peer Reviewed
• [Presentation] 20.DPP-4阻害薬による抗炎症効果 (2015)
  • Author(s): 浅野知一郎
  • Organizer: 第53回日本糖尿病学会九州地方会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-27
  • Invited
• [Presentation] マクロファージにおける糖代謝による活性酸素産生とインスリン抵抗性 (2015)
  • Author(s): 櫛山暁史、菊池貴子、迫田秀之、藤城緑、山本屋武、山崎広貴、中津祐介、浅野地一郎、河津捷二
  • Organizer: 第５８回日本糖尿病学会年次学術集会
  • Place of Presentation: 下関
  • Year and Date: 2015-05-21
• [Presentation] 高脂肪食負荷による近位筋優位遺伝性運動感覚ニューロパチー原因遺伝子TFGの発現低下とその病的意義 (2015)
  • Author(s): 浅野知一郎、松永泰花、迫田秀之、櫛山暁史、藤城緑、山本屋武、鎌田英明、小野啓、中津祐介
  • Organizer: 第５８回日本糖尿病学会年次学術集会
  • Place of Presentation: 下関
  • Year and Date: 2015-05-21
• [Presentation] 性ホルモン結合グルブリン(SHBG)の代謝への影響の検討 (2015)
  • Author(s): 山崎広貴、櫛山暁史、迫田秀之、藤城緑、山本屋武、菊池貴子、金子直、浅野知一郎
  • Organizer: 第５８回日本糖尿病学会年次学術集会
  • Place of Presentation: 下関
  • Year and Date: 2015-05-21
• [Presentation] DPP4阻害薬anagliptineはLPS投与マウスの肝臓・脂肪組織における炎症反応を抑制する (2015)
  • Author(s): 新城尊徳、岩下未咲、中津祐介、鎌田英明、迫田秀之、藤城緑、櫛山暁史、浅野知一郎、西村英紀
  • Organizer: 第５８回日本糖尿病学会年次学術集会
  • Place of Presentation: 下関
  • Year and Date: 2015-05-21
• [Presentation] 膵β細胞機能におけるプロリン異性化酵素Pin1の役割 (2015)
  • Author(s): 中津祐介、森馨一、松永泰花、山本屋武、迫田秀之、藤城緑、櫛山暁史、石原寿光、浅野知一郎
  • Organizer: 第５８回日本糖尿病学会年次学術集会
  • Place of Presentation: 下関
  • Year and Date: 2015-05-21
• [Presentation] 肝臓におけるLUBAC(linear ubiquitin assembly complex)活性低下はAkt-mTOR経路の亢進および肝での炎症を惹起する (2015)
  • Author(s): 山本屋武、迫田秀之、藤城緑、山崎広貴、金子直、菊池貴子、櫛山暁史、浅野知一郎
  • Organizer: 第５８回日本糖尿病学会年次学術集会
  • Place of Presentation: 下関
  • Year and Date: 2015-05-21
• [Presentation] SGLT2阻害薬ルセオグリフロジンによる非アルコール性脂肪性肝炎の改善作用 (2015)
  • Author(s): 藤城緑、中津祐介、迫田秀之、櫛山暁史、松永泰花、山本屋武、鎌田英明、浅野知一郎
  • Organizer: 第５８回日本糖尿病学会年次学術集会
  • Place of Presentation: 下関
  • Year and Date: 2015-05-21
• [Presentation] キサンチンオキシダーゼ阻害剤FebuxostatによるNASH改善作用の検討 (2015)
  • Author(s): 松永泰花、中津祐介、迫田秀之、櫛山暁史、藤城緑、山本屋武、鎌田英明、新城尊徳、岩下未咲、西村英紀、小野啓、浅野知一郎
  • Organizer: 第５８回日本糖尿病学会年次学術集会
  • Place of Presentation: 下関
  • Year and Date: 2015-05-21
• [Presentation] 膵β細胞からのインスリン分泌におけるプロリン異性化酵素Pin1の役割 (2014)
  • Author(s): 浅野知一郎、松永泰花、福嶋俊明、山崎広貴、山本屋武、櫛山暁史、中津祐介
  • Organizer: 第５７回日本糖尿病学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] キサンチンオキシダーゼ阻害剤FebuxostatによるNASH改善作用の検討 (2014)
  • Author(s): 藤城緑、中津祐介、福嶋俊明、松永泰花、迫田秀之、櫛山暁史、山本屋武、西村英紀、浅野知一郎
  • Organizer: 第５７回日本糖尿病学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] LUBAC (linear ubiquitin chain assembly complex)のインスリンシグナル伝達系における役割の検討 (2014)
  • Author(s): 山本屋武、迫田秀之、藤城緑、山崎広貴、菊池貴子、櫛山暁史、浅野知一郎
  • Organizer: 第５７回日本糖尿病学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] マクロファージresistin like molecule βによるインスリン抵抗性・動脈硬化発症の機序 (2014)
  • Author(s): 櫛山暁史、菊池貴子、迫田秀之、藤城緑、山崎広貴、山本屋武、大久保博史、中津祐介、河津捷二、浅野知一郎
  • Organizer: 第５７回日本糖尿病学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] CC7経路が肥満およびインスリン抵抗性に及ぼす影響に関する検討 (2014)
  • Author(s): 岩下未咲、佐野朋美、新城尊徳、箸方厚之、浅野知一郎、西村英紀
  • Organizer: 第５７回日本糖尿病学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] DPP4阻害薬anagliptinは、活性化マクロファージおよびマクロファージ共培養下脂肪細胞の炎症反応を抑制する (2014)
  • Author(s): 新城尊徳、岩下未咲、中津祐介、迫田秀之、藤城緑、櫛山暁史、鎌田英明、西村英紀、浅野知一郎
  • Organizer: 第５７回日本糖尿病学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] Pin1阻害薬Jugloneを用いたNASH治療効果の検討 (2014)
  • Author(s): 山崎広貴、中津祐介、鎌田英明、西村英紀、菊池貴子、藤城緑、迫田秀之、浅野知一郎
  • Organizer: 第５７回日本糖尿病学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] プロリン異性化酵素Pin1はAMPKγ subunitに結合し、活性を抑制する (2014)
  • Author(s): 中津祐介、岩下未咲、福嶋俊明、菊池貴子、櫛山暁史、迫田秀之、浅野知一郎
  • Organizer: 第５７回日本糖尿病学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] 非アルコール性脂肪性肝炎発症におけるLUBAC形成障害の役割 (2014)
  • Author(s): 松永泰花、中津祐介、鎌田英明、福嶋俊明、岩下未咲、新城尊徳、菊池貴子、藤城緑、浅野知一郎
  • Organizer: 第５７回日本糖尿病学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Book] SGLT2阻害薬のすべて (2014)
  • Author(s): 浅野 知一郎、中津 祐介
  • Total Pages: 200
  • Publisher: 先端医学社
• [Patent(Industrial Property Rights)] Pin1 阻害薬を用いた炎症性腸疾患の治療または予防方法 (2014)
  • Inventor(s): 浅野知一郎、中津祐介
  • Industrial Property Rights Holder: 浅野知一郎、中津祐介
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-10-29