Elucidation of the role of CITED2 in hepatic glucose production

• Project/Area Number: 21591155
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Research Institute, International Medical Center of Japan
• Principal Investigator: MATSUMOTO Michihiro 独立行政法人国立国際医療研究センター, 研究所・糖尿病研究センター・分子代謝制御研究部, 部長 (90467663)
• Co-Investigator(Kenkyū-buntansha): INAGAKI Kenjiro 国立国際医療センター, 研究所・臨床薬理研究部, 室長 (80533736)
• Research Collaborator: SAKAI Mashito ; TSUJIMURA Tomoko ; CAO Yongheng
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: CITED2 / 遺伝子転写 / 糖尿病 / インスリン / グルカゴン / 肝糖産生 / ノックアウトマウス

Research Abstract

We unveiled that CITED2 functions as a transducer of glucagon and insulin signaling in the regulation of PGC-1αactivity that is associated with the transcriptional control of gluconeogenesis and that this function is mediated through the modulation of GCN5-dependent PGC-1αacetylation. We also found that loss of hepatic CITED2 function suppresses gluconeogenesis in diabetic mice, suggesting it as a therapeutic target for hyperglycemia.

Research Products

• [Journal Article] CITED2 links hormonal signaling to PGC-1αacetylation in the regulation of gluconeogenesis (2012)
  • Author(s): Sakai M, Matsumoto M, Tujimura T, Yongheng C, Inagaki K, Kasuga M., 他8名
  • Journal Title: Nat Med Volume: 18(4) Issue: 4 Pages: 612-7
  • DOI: 10.1038/nm.2691
  • Peer Reviewed
• [Journal Article] Endoplasmic reticulum stress inhibits STAT3-dependent suppression of hepatic gluconeogenesis via dephosphorylation and deacetylation (2012)
  • Author(s): Kimura K, Yamada T, Matsumoto M, Kasuga M, Inoue H., 他9名
  • Journal Title: Diabetes Volume: 61 Issue: 1 Pages: 61-73
  • DOI: 10.2337/db10-1684
  • Peer Reviewed
• [Journal Article] Endoplasmic Reticulum Stress Inhibits STAT3-Dependent Suppression of Hepatic Gluconeogenesis via Dephosphorylation and Deacetylation (2012)
  • Author(s): Kimura K, Yamada T, Matsumoto M, Kido Y, Hosooka T, Asahara S, Matsuda T, Ota T, Watanabe H, Sai Y, Miyamoto K, Kaneko S, Kasuga M, Inoue H
  • Journal Title: Diabetes Volume: 61 Pages: 61-73
  • Peer Reviewed
• [Journal Article] Overexpression of KLF15 in adipocytes of mice results in down-regulation of SCD1 expression in adipocytes and consequent enhancement of glucose-induced insulin secretion (2011)
  • Author(s): Nagare T, Sakaue H, et al
  • Journal Title: J Biol Chem Volume: Vol.286 Issue: 43 Pages: 37458-37469
  • DOI: 10.1074/jbc.m111.242651
  • Peer Reviewed
• [Journal Article] Ablation of TSC2 enhances insulin secretion by increasing the number of mitochondria through activation of mTORC1 (2011)
  • Author(s): Koyanagi M, Asahara S, Matsuda T, Hashimoto N, Shigeyama Y, Shibutani Y, Kanno A, Fuchita M, Mikami T, Matsumoto M, Kasuga M, Kido Y
  • Journal Title: PLoS One Volume: 6
  • URL: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0023238
  • Peer Reviewed
• [Journal Article] Overexpression of KLF15 in adipocytes of mice results in down-regulation of SCD1 expression in adipocytes and consequent enhancement of glucose-induced insulin secretion (2011)
  • Author(s): Nagare T, Sakaue H, Matsumoto M, Cao Y, Inagaki K, Sakai M, Takashima Y, Nakamura K, Mori T, Okada Y, Matsuki Y, Watanabe E, Ikeda K, Taguchi R, Kamimura N, Ohta S, Hiramatsu R, Kasuga M
  • Journal Title: J Biol Chem Volume: 286 Pages: 37458-37469
  • Peer Reviewed
• [Journal Article] Ablation of TSC2 Enhances Insulin Secretion by Increasing the Number of Mitochondria through Activation of mTORC1 (2011)
  • Author(s): Koyanagi M, Asahara S, Matsuda T, Hashimoto N, Shigeyama Y, Shibutani Y, Kanno A, Fuchita M, Mikami T, Hosooka T, Inoue H, Matsumoto M, Koike M, Uchiyama Y, Noda T, Seino S, Kasuga M, Kido Y
  • Journal Title: PLoS One Volume: 6
  • Peer Reviewed
• [Journal Article] HDACs confer glucagon responsiveness to FoxO for gluconeogenesis (2011)
  • Author(s): Matsunaoto M
  • Journal Title: Diabetology International Volume: 2 Pages: 109-111
  • Peer Reviewed
• [Journal Article] Ablation of C/EBP alleviates ER stress and pancreatic β cell failure through the GRP78 chaperone in mice. (2010)
  • Author(s): Matsuda T, 他
  • Journal Title: Journal of Clinical Investigation Volume: 120 Pages: 115-126
  • Peer Reviewed
• [Journal Article] PDK1/FoxO1 pathway in POMC neurons regulates Pomc expression and food intake. (2010)
  • Author(s): Iskandar K, 他
  • Journal Title: Am J physiol Endocrinol Metab. Volume: 298
  • Peer Reviewed
• [Journal Article] Ablation of C/EBP alleviates ER stress and pancreatic β cell failure through the GRP78 chaperone in mice (2010)
  • Author(s): Matsuda T, 他
  • Journal Title: Journal of Clinical Investigation 120 Pages: 115-126
  • Peer Reviewed
• [Journal Article] Foxo1 links hyperglycemia to LDL oxidation and endothelial nitric oxide synthase dysfunction in vascular endothelial cells (2009)
  • Author(s): Tanaka J, 他
  • Journal Title: Diabetes 58 Pages: 2344-54
  • Peer Reviewed
• [Presentation] CITED2はホルモン応答性にPGC-1αのアセチル化を調節し、肝糖産生を制御する (2012)
  • Author(s): 酒井真志人
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2012-05-19
• [Presentation] CITED2はホルモン応答性にPGC-1αのアセチル化を調節し、肝糖産生を制御する (2012)
  • Author(s): 酒井真志人
  • Organizer: 第49回日本臨床分子医学会学術総会
  • Place of Presentation: 京都
  • Year and Date: 2012-04-13
• [Presentation] CITED2 links hormonal signals to PGC-1αacetylation for regulating fasting gluconeogenesis (2012)
  • Author(s): Matsumoto M
  • Organizer: Keystone Symposia, Pathogenesis of Diabetes : Emerging Insights into Molecular Mechanisms
  • Place of Presentation: Santa Fe, New Mexico, USA
  • Year and Date: 2012-02-01
• [Presentation] CITED2 links hormonal signals to PGC-1α acetylation for regulating fasting gluconeogenesis (2012)
  • Author(s): Matsumoto M, Sakai M, Kasuga M
  • Organizer: Keystone Symposia, Pathogenesis of Diabetes : Emerging Insights into Molecular Mechanisms
  • Place of Presentation: Santa Fe, New Mexico, USA
  • Year and Date: 2012-02-01
• [Presentation] 糖尿病の薬物療法-現況と今後の展望 (2011)
  • Author(s): 松本道宏
  • Organizer: 第20回国際医療協力シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2011-11-18
• [Presentation] CITED2はホルモン応答性にPGC-1αのアセチル化を調節し、肝糖産生を制御する (2011)
  • Author(s): 酒井真志人
  • Organizer: 第32回日本肥満学会
  • Place of Presentation: 兵庫県淡路市
  • Year and Date: 2011-09-23
• [Presentation] CITED2はホルモン応答性にPGC-1αのアセチル化を調節し、肝糖産生を制御する (2011)
  • Author(s): 酒井真志人, 松本道宏, 辻村知子, 曹永恒, 稲垣健二郎, 細岡哲也, 井上啓, 春日雅人
  • Organizer: 第32回日本肥満学会
  • Place of Presentation: 淡路
  • Year and Date: 2011-09-23
• [Presentation] 脂肪細胞における転写因子KLF15の過剰発現はSCD1発現を抑制し、インスリン分泌を増加させる (2011)
  • Author(s): 永礼智基, 阪上浩, 松本道宏, 曹永恒, 酒井真志人, 稲垣健二郎, 松木泰, 渡辺英二郎, 池田和貴, 田口良, 上村尚美, 太田成男, 平松隆司, 春日雅人
  • Organizer: 第32回日本肥満学会
  • Place of Presentation: 淡路
  • Year and Date: 2011-09-23
• [Presentation] CITED2 links hormonal signals to PGC-1αacetylation for regulating fasting gluconeogenesis (2011)
  • Author(s): Sakai M
  • Organizer: 47th EASD Annual Meeting
  • Place of Presentation: Lisbon, Portugal
  • Year and Date: 2011-09-13
• [Presentation] CITED2 links hormonal signals to PGC-1α acetylation for regulating fasting gluconeogenesis (2011)
  • Author(s): Sakai M, Matsumoto M, Kasuga M
  • Organizer: 47th EASD Annual Meeting
  • Place of Presentation: Lisbon, Portugal
  • Year and Date: 2011-09-13
• [Presentation] 肝臓におけるエネルギー代謝調節-肝糖産生と脂肪肝を中心に- (2011)
  • Author(s): 松本道宏
  • Organizer: 第5回神戸生活習慣病研究会
  • Place of Presentation: 神戸
  • Year and Date: 2011-07-23
• [Presentation] 転写共役因子CITED2はPGC-1αの活性調節を介して肝糖代謝を制御する (2011)
  • Author(s): 酒井真志人, 松本道宏, 辻村知子, 曹永恒, 稲垣健二郎, 細岡哲也, 井上啓, 春日雅人
  • Organizer: 第84回日本内分泌学会学術総会若手研究奨励賞審査講演
  • Place of Presentation: 神戸
  • Year and Date: 2011-04-22
• [Presentation] 小胞体ストレスは、アセチル化抑制を介して、STAT3依存性の肝糖新生系酵素遺伝子発現抑制を阻害する (2011)
  • Author(s): 木村久美, 井上啓, 松本道宏, 春日雅人
  • Organizer: 第84回日本内分泌学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 2011-04-22
• [Presentation] 転写共役因子CITED2による肝臓の糖代謝制御機構の解明 (2011)
  • Author(s): 松本道宏
  • Organizer: 第84回日本内分泌学会学術総会シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2011-04-21
• [Presentation] 転写共役因子CITED2による肝臓の糖代謝制御機構の解明 (2011)
  • Author(s): 酒井真志人, 松本道宏, 他
  • Organizer: 第5回炎症・脂質代謝・メタボリサーチフォーラム
  • Place of Presentation: 東京
  • Year and Date: 2011-02-12
• [Presentation] 遺伝子転写による肝代謝調節機構 (2011)
  • Author(s): 松本道宏
  • Organizer: 「食」による生活習慣病予防医学の展開
  • Place of Presentation: 金沢
  • Year and Date: 2011-02-03
• [Presentation] 転写共役因子CITED2はPGC-1αの活性調節を介して肝糖代謝を制御する (2010)
  • Author(s): 酒井真志人, 松本道宏, 他
  • Organizer: 第22回分子糖尿病学シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2010-12-04
• [Presentation] Cited2 Regulates Hepatic Gluconeogenesis by Controlling PGC-1αActivity (2010)
  • Author(s): Sakai M
  • Organizer: 11th International Symposium on Insulin Receptor AND Insulin Action
  • Place of Presentation: Naples, Italy
  • Year and Date: 2010-10-30
• [Presentation] Cited2 Regulates Hepatic Gluconeogenesis by Controlling PGC-1α Activity. (2010)
  • Author(s): 酒井真志人, 松本道宏, 春日雅人
  • Organizer: 11th International Symposium on Insulin Receptor and Insulin Action
  • Place of Presentation: ナポリ、イタリア
  • Year and Date: 2010-10-30
• [Presentation] The Transcriptional Coactivator Cited2 Regulates Hepatic Gluco-neogenesis by Controlling PGC-1α Activity. (2010)
  • Author(s): 松本道宏, 酒井真志人, 春目雅人
  • Organizer: The 6th Scientific Meeting of APDO Study Group
  • Place of Presentation: シンガポール
  • Year and Date: 2010-08-27
• [Presentation] The transcriptional Coactivator Cited2 regulates hepatic gluconeogenesis by controlling PGC-1αactivity (2010)
  • Author(s): 松本道宏
  • Organizer: 第53回日本糖尿病学会年次学術集会シンポジウム
  • Place of Presentation: 岡山
  • Year and Date: 2010-05-28
• [Presentation] The transcriptional Coactivator Cited2 regulates hepatic gluconeo-genesis by controlling PGC-α activity. (2010)
  • Author(s): 松本道宏, 酒井真志人, 春日雅人
  • Organizer: 第53回日本糖尿病学会年次学術集会シンポジウム
  • Place of Presentation: 岡山
  • Year and Date: 2010-05-28
• [Presentation] 転写共役因子CITED2はPGC-1αの活性調節を介して肝糖産生を制御する (2010)
  • Author(s): 酒井真志人, 松本道宏, 他
  • Organizer: 第53回日本糖尿病学会年次学術集会シンポジウム
  • Place of Presentation: 岡山
  • Year and Date: 2010-05-27
• [Presentation] 転写共役因子CITED2はPGC-1αの活性調節を介して肝糖代謝を制御する (2010)
  • Author(s): 酒井真志人, 松本道宏, 他
  • Organizer: 第47回日本臨床分子医学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-04-11
• [Book] 糖尿病学イラストレイテッド,糖代謝における肝臓の役割 (2012)
  • Author(s): 松本道宏
  • Publisher: 羊土社
• [Book] 糖尿病学イラストレイテッド.糖代謝における肝臓の役割 (2012)
  • Author(s): 春日雅人, 松本道宏, 他
  • Total Pages: 308
  • Publisher: 羊土社
• [Book] 糖代謝調節の分子機構(総論),糖尿病ナビゲーター第2版 (2010)
  • Author(s): 松本道宏,春日雅人
  • Publisher: メディカルレビュー社
• [Book] 糖尿病ナビゲーター(第2版)糖代謝調節の分子機構(総論) (2010)
  • Author(s): 松本道宏、春日雅人
  • Publisher: メディカルレビュー社
• [Remarks]
  • URL: http://www.ncgm.go.jp/rese/top/j/news/news0028.html
• [Remarks]
  • URL: http://www.ncgm.go.jp/rese/top/j/news/news0028.html