2023/04/13 更新

写真a

タケナカ　ノブユキ
竹中　延之
Takenaka Nobuyuki
担当
大学院理学研究科 生物化学専攻 准教授
理学部 生物化学科
職名
准教授
所属
理学研究院
連絡先
メールアドレス
ホームページ
http://www.b.s.osakafu-u.ac.jp/~tsato/index.html
所属キャンパス
中百舌鳥キャンパス

担当・職階

  • 大学院理学研究科 生物化学専攻 

    准教授  2022年04月 - 継続中

  • 理学部 生物化学科 

    准教授  2022年04月 - 継続中

取得学位

  • 修士（バイオメディカルサイエンス） （ 神戸大学 ）

  • 博士（医学） （ 神戸大学 ）

研究分野

  • ライフサイエンス / 分子生物学  / 分子生物学

  • ライフサイエンス / 細胞生物学  / 細胞生物学

  • ライフサイエンス / 細胞生物学

  • ライフサイエンス / 分子生物学

研究キーワード

  • 骨格筋、脂肪細胞、白色脂肪細胞、褐色脂肪細胞、Rac1、GLUT4、CD36、FATP1、低分子量GTP結合タンパク質、グルコース取込み、脂肪酸、インスリン、肥満、糖尿病、NAFLD、脂肪肝、細胞内シグナル伝達、肝臓、ノックアウトマウス

研究概要

  • 肥満、糖尿病発症におけるRac1の関与

  • 温度刺激応答シグナル伝達機構の解明

  • 脂肪細胞における糖取り込みシグナル伝達機構の解明

  • 骨格筋における糖取り込みシグナル伝達機構の解明

所属学協会

  • 日本生化学会

  • 日本分子生物学会

論文

  • Regulation of De Novo Lipid Synthesis by the Small GTPase Rac1 in the Adipogenic Differentiation of Progenitor Cells from Mouse White Adipose Tissue

    Hasegawa K.

    International Journal of Molecular Sciences   24 ( 5 )   2023年03月（ ISSN:16616596 ）

    　詳細を見る

  • Atrophy of White Adipose Tissue Accompanied with Decreased Insulin-Stimulated Glucose Uptake in Mice Lacking the Small GTPase Rac1 Specifically in Adipocytes. 査読

    Kiko Hasegawa, Nobuyuki Takenaka, Kenya Tanida, Man Piu Chan, Mizuki Sakata, Atsu Aiba, Takaya Satoh

    International journal of molecular sciences   22 ( 19 )   2021年10月

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    掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

    Insulin stimulates glucose uptake in adipose tissue and skeletal muscle by inducing plasma membrane translocation of the glucose transporter GLUT4. Although the small GTPase Rac1 is a key regulator downstream of phosphoinositide 3-kinase (PI3K) and the protein kinase Akt2 in skeletal muscle, it remains unclear whether Rac1 also regulates glucose uptake in white adipocytes. Herein, we investigated the physiological role of Rac1 in white adipocytes by employing adipocyte-specific rac1 knockout (adipo-rac1-KO) mice. Subcutaneous and epididymal white adipose tissues (WATs) in adipo-rac1-KO mice showed significant reductions in size and weight. Actually, white adipocytes lacking Rac1 were smaller than controls. Insulin-stimulated glucose uptake and GLUT4 translocation were abrogated in rac1-KO white adipocytes. On the other hand, GLUT4 translocation was augmented by constitutively activated PI3K or Akt2 in control, but not in rac1-KO, white adipocytes. Similarly, to skeletal muscle, the involvement of another small GTPase RalA downstream of Rac1 was demonstrated. In addition, mRNA levels of various lipogenic enzymes were down-regulated in rac1-KO white adipocytes. Collectively, these results suggest that Rac1 is implicated in insulin-dependent glucose uptake and lipogenesis in white adipocytes, and reduced insulin responsiveness due to the deficiency of Rac1 may be a likely explanation for atrophy of WATs.

    DOI： 10.3390/ijms221910753

    PubMed

  • The guanine nucleotide exchange factor FLJ00068 activates Rac1 in adipocyte insulin signaling. 査読

    Nobuyuki Takenaka, Mika Nakao, Kiko Hasegawa, Man Piu Chan, Takaya Satoh

    FEBS letters   594 ( 24 )   4370 - 4380   2020年12月

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    掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

    Insulin stimulates glucose uptake via the translocation of the glucose transporter GLUT4 to the plasma membrane in adipocytes. Several lines of evidence suggest that the small GTPase Rac1 plays an important role in insulin-stimulated glucose uptake in skeletal muscle and adipocytes. The purpose of this study is to investigate the mechanisms whereby Rac1 is regulated in adipocyte insulin signaling. Here, we show that knockdown of the guanine nucleotide exchange factor FLJ00068 inhibits Rac1 activation and GLUT4 translocation by insulin and a constitutively activated form of the protein kinase Akt2. Furthermore, constitutively activated FLJ00068 induced Rac1 activation and Rac1-dependent GLUT4 translocation. Collectively, these results suggest the involvement of FLJ00068 downstream of Akt2 in insulin-stimulated glucose uptake signaling in adipocytes.

    DOI： 10.1002/1873-3468.13939

    PubMed

  • A Crucial Role for the Small GTPase Rac1 Downstream of the Protein Kinase Akt2 in Insulin Signaling that Regulates Glucose Uptake in Mouse Adipocytes. 査読

    Nobuyuki Takenaka, Mika Nakao, Sayaka Matsui, Takaya Satoh

    International journal of molecular sciences   20 ( 21 )   2019年10月

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    掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

    Insulin-stimulated glucose uptake is mediated by translocation of the glucose transporter GLUT4 to the plasma membrane in adipocytes and skeletal muscle cells. In both types of cells, phosphoinositide 3-kinase and the protein kinase Akt2 have been implicated as critical regulators. In skeletal muscle, the small GTPase Rac1 plays an important role downstream of Akt2 in the regulation of insulin-stimulated glucose uptake. However, the role for Rac1 in adipocytes remains controversial. Here, we show that Rac1 is required for insulin-dependent GLUT4 translocation also in adipocytes. A Rac1-specific inhibitor almost completely suppressed GLUT4 translocation induced by insulin or a constitutively activated mutant of phosphoinositide 3-kinase or Akt2. Constitutively activated Rac1 also enhanced GLUT4 translocation. Insulin-induced, but not constitutively activated Rac1-induced, GLUT4 translocation was abrogated by inhibition of phosphoinositide 3-kinase or Akt2. On the other hand, constitutively activated Akt2 caused Rac1 activation, and insulin-induced Rac1 activation was suppressed by an Akt2-specific inhibitor. Moreover, GLUT4 translocation induced by a constitutively activated mutant of Akt2 or Rac1 was diminished by knockdown of another small GTPase RalA. RalA was activated by a constitutively activated mutant of Akt2 or Rac1, and insulin-induced RalA activation was suppressed by an Akt2- or Rac1-specific inhibitor. Collectively, these results suggest that Rac1 plays an important role in the regulation of insulin-dependent GLUT4 translocation downstream of Akt2, leading to RalA activation in adipocytes.

    DOI： 10.3390/ijms20215443

    PubMed

  • A critical role for the small GTPase Rac1 in insulin signaling that regulates glucose uptake in skeletal muscle 査読

    Satoh, T., and Takenaka, N.

    Research on Chemical Intermediates An International Journal   2019年07月

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    共著区分：共著  

  • Involvement of the protein kinase Akt2 in insulin-stimulated Rac1 activation leading to glucose uptake in mouse skeletal muscle

    Takenaka, N., Araki、N., and Satoh, T.

    PLOS ONE 著書   2019年02月

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    共著区分：共著  

  • Involvement of the protein kinase Akt2 in insulin-stimulated Rac1 activation leading to glucose uptake in mouse skeletal muscle. 査読

    Nobuyuki Takenaka, Natsumi Araki, Takaya Satoh

    PloS one   14 ( 2 )   e0212219   2019年

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    掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

    Translocation of the glucose transporter GLUT4 to the sarcolemma accounts for glucose uptake in skeletal muscle following insulin administration. The protein kinase Akt2 and the small GTPase Rac1 have been implicated as essential regulators of insulin-stimulated GLUT4 translocation. Several lines of evidence suggest that Rac1 is modulated downstream of Akt2, and indeed the guanine nucleotide exchange factor FLJ00068 has been identified as an activator of Rac1. On the other hand, the mechanisms whereby Akt2 and Rac1 are regulated in parallel downstream of phosphoinositide 3-kinase are also proposed. Herein, we aimed to provide additional evidence that support a critical role for Akt2 in insulin regulation of Rac1 in mouse skeletal muscle. Knockdown of Akt2 by RNA interference abolished Rac1 activation following intravenous administration of insulin or ectopic expression of a constitutively activated phosphoinositide 3-kinase mutant. The activation of another small GTPase RalA and GLUT4 translocation to the sarcolemma following insulin administration or ectopic expression of a constitutively activated form of phosphoinositide 3-kinase, but not Rac1, were also diminished by downregulation of Akt2 expression. Collectively, these results strongly support the notion that Rac1 acts downstream of Akt2 leading to the activation of RalA and GLUT4 translocation to the sarcolemma in skeletal muscle.

    DOI： 10.1371/journal.pone.0212219

    PubMed

  • ACK1.“Encyclopedia of Signaling Molecules” (2nd Edition, Sangdun Choi, ed; Springer Nature) 査読

    Takenaka, N., and Satoh, T

    Springer Nature   2017年09月

  • In situ detection of the activation of Rac1 and RalA small GTPases in mouse adipocytes by immunofluorescent microscopy following in vivo and ex vivo insulin stimulation. 査読

    Takenaka, N., Nihata, Y., Ueda, S., and Satoh, T.

    Cellular Signaling   39   2017年07月

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    共著区分：共著  

  • Rac1 activation caused by membrane translocation of a guanine nucleotide exchange factor in Akt2-mediated insulin signaling in mouse skeletal muscle. 査読

    Takenaka, N., Nihata, Y., and Satoh, T

    PLOS ONE 著書   11 ( 5 )   2016年05月

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    共著区分：共著  

  • Role for RalA downstream of Rac1 in skeletal muscle insulin signalling.

    Takenaka, N., Sumi, T., Matsuda, K., Fujita, J., Hosooka, T., Noguchi, T., Aiba, A., and Satoh, T

    Biochemical Journal 著書   469 ( 3 )   2015年07月

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    共著区分：共著  

  • Immunofluorescent detection of the activation of the small GTPase Rac1 in mouse skeletal muscle fibers. 査読

    Takenaka, N., Nihata, Y., and Satoh, T

    Analytical Biochemistry   476   2014年09月

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    共著区分：共著  

  • Phospholipase Cε, an effector of Ras and Rap small GTPases, is required for airway inflammatory response in a mouse model of bronchial asthma. 査読

    Nagano, T., Edamatsu, H., Kobayashi, K., Takenaka, N., Yamamoto, M., Sasaki, N., Nishimura, Y., and Kataoka, T.

    PLOS ONE 雑誌   9 ( 9 )   2014年09月

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    共著区分：共著  

  • A critical role of the small GTPase Rac1 in Akt2-mediated GLUT4 translocation in mouse skeletal muscle. 査読

    Takenaka, N., Izawa, R., Wu, J., Kitagawa, K., Nihata, Y., Hosooka, T., Noguchi, T., Ogawa, W., Aiba, A., and Satoh, T.

    FEBS J. 雑誌 Wiley   281   2014年01月

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    共著区分：共著  

  • Role of the guanine nucleotide exchange factor in Akt2-mediated plasma membrane translocation of GLUT4 in insulin-stimulated skeletal muscle 査読

    Takenaka, N., Yasuda, N., Nihata, Y., Hosooka, T., Noguchi, T., Aiba, A., and Satoh, T.

    Cellular Signalling 雑誌 ELSEVIER   2014年

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    共著区分：共著  

  • MDCK cell culture-derived formalin-inactivated influenza whole virion vaccine from an influenza virus library conferred cross-protective immunity by intranasal administration in mice 査読

    Haredy,A., Takenaka,N.,Yamada,H., Sakoda,Y., Okamatsu,M., Yamamoto,N., Omasa,T., Ohtake,H.,Mori,Y.,Kida,H., Yamanishi,K.,Okamoto,S

    Clinical and Vaccine Immunology 雑誌 ASM press   20 ( 7 )   2013年05月

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    共著区分：共著  

  • Akt2 regulates Rac1 activity in the insulin-dependent signaling pathway leading to GLUT4 translocation to the plasma membrane in skeletal muscle cells. 査読

    Nozaki, S, Takeda, T, Kitaura, T, Takenaka, N., Kataoka, T. and Satoh

    Cellular Signalling 雑誌 ELSEVIER   25   2013年03月

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    共著区分：共著  

  • Comparison of the cross-reactive anti-influenza neutralizing activity of polymeric and monomeric IgA monoclonal antibodies. 査読

    Tanimoto, T., Haredy, A., Takenaka, N., Tamura, S., Okuno, Y., Mori, Y., Yamanishi, K., and Okamoto, S.

    Viral immune. 雑誌 Mary ann libert   25 ( 5 )   2012年10月

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    共著区分：共著  

  • Influenza virus neuraminidase contributes to the dextran sulfate-dependent suppressive replication of some influenza A virus strains. 査読

    Yamada, H., Haredy, A., Takenaka, N., Mori, Y., Yamanishi, K., and Okamoto, S.

    Antiviral research 雑誌 ELSEVIER   96 ( 3 )   2012年09月

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    共著区分：共著  

  • Complementation of the function of glycoprotein H of human herpesvirus-6 variant A by glycoprotein H of variant B in the viral life cycle. 査読

    Oyaizu, H., Tang, H., Ota, M., Takenaka, N., Ozono, K., Yamanishi K., and Moir, Y.

    Journal of Virology 雑誌 ASM press   86 ( 16 )   2012年08月

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    共著区分：共著  

  • Role of RalA downstream of Rac1 in insulin-dependent glucose uptake in muscle cells. 査読

    Nozaki, S, Ueda, S., Takenaka, N., Kataoka, T. and Satoh, T

    Cellular Signalling 雑誌 ELSEVIER   24   2012年07月

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    共著区分：共著  

  • Intranasal immunization with formalin-inactivated human influenza A whole-virion vaccine alone or split-virion vaccine with mucosal adjuvants show similar cross-protection. 査読

    Okamoto, S., Matsuoka, S., Takenaka, N., Haredy, A., Tanimoto, T., Gomi, Y., Ishikawa, T.,Akagi, T., Akashi, M., Okuno, Y., Mori, Y. and Yamanishi, K.

    Clinical and Vaccine Immunology 雑誌 ASM press   19 ( 7 )   2012年05月

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    共著区分：共著  

  • Phospholipase Ce as a potential molecular target for anti-inflammatory therapy and cancer prevention. 査読

    Edamatsu, H., Takenaka, N., Hu, L. and Kataoka

    Inflammation and regeneration 雑誌 J-Stage   31   2011年11月

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    共著区分：共著  

  • Phospholipase Cε plays a crucial role in ultraviolet B-induced neutrophil-associated skin inflammation by regulating the expression of CXCL1/KC. 査読

    Oka, M., Edamatsu, H., Kunisada, M., Hu, L., Takenaka, N., Sakaguchi, M., Kataoka, T., and Nishigori, C.

    Laboratory Investigation 雑誌 nature   91   2011年02月

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    共著区分：共著  

  • Overexpression of phospholipase Ce in keratinocytes upregulates cytokine expression and causes dermatitis with acanthosis and T-cell infiltration. 査読

    Takenaka, N., Edamatsu, H., Suzuki, N., Saito, H., Inoue, Y., Oka, M., Hu, L., and Kataoka, T.

    European journal of imunology 雑誌 Wiley   41 ( 1 )   2011年01月

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    共著区分：共著  

  • Enhancement of ultraviolet B-induced skin tumor development in phospholipase Cε-knockout mice is associated with decreased cell death. 査読

    Oka, M., Edamatsu, H., Kunisada, M., Hu, L., Takenaka, N., Dien, S., Sakaguchi, M., Kitazawa, R., Norose, K., Kataoka, T., and Nishigori, C

    Carcinogenesis 雑誌 Oxford journal   31 ( 10 )   2010年08月

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    共著区分：共著  

  • Crucial role of phospholipase Ce in induction of local skin inflammatory reactions in the elicitation stage of allergic contact hypersensitivity. 査読

    Hu, L., Edamatsu, H., Takenaka, N., Ikuta, S., and Kataoka, T.

    Eur. J. Immunol. 雑誌 Wiley   184 ( 2 )   2010年01月

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    共著区分：共著  

▼全件表示

書籍等出版物

  • バイオサイエンス実験　入門から応用へ

    石原　道博, 居原　秀, 恩田　真紀, 川西　優喜, 木下　誉富, 児玉　靖司, 佐藤　孝哉, 白石　一乗, 竹田　恵美, 竹中　延之, 円谷　健, 西野　貴子, 原　正之, 藤井　郁雄, 藤原　大祐, 森　英樹, 八木　孝司, 吉原　静恵（ 担当： 共著）

    大阪公立大学共同出版会  2016年03月 

講演・口頭発表等

▼全件表示

産業財産権等

  • 脂肪酸トランスポーターの細胞内動態の分析方法、及び脂肪酸トランスポーター改変タンパク質の利用

    竹中延之、佐藤孝哉

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    産業財産権の種類：特許権 

    出願番号：特願2021-028920 

    公開番号：特開2022-129999 

担当授業科目

  • 細胞生物学特論

    2021年度    

  • 生化学I

    2021年度    

  • 初年次ゼミナール【生活習慣病を知る・考える】

    2021年度    

  • 生物学実験

    2021年度   実習  

  • 分子生物学I

    2021年度