Elucidation of growth mechanisms of pancreatic .-cells with new developed procedures

• Project/Area Number: 21689007
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: General physiology
• Research Institution: Gunma University
• Principal Investigator: TORII Seiji 群馬大学, 生体調節研究所, 准教授 (40312904)
• Co-Investigator(Renkei-kenkyūsha): YAMADA Keiichi 群馬大学, 工学研究科, 助教 (70323334)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥23,270,000 (Direct Cost: ¥17,900,000、Indirect Cost: ¥5,370,000); Fiscal Year 2011: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000); Fiscal Year 2010: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000); Fiscal Year 2009: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
• Keywords: インスリン / 脱リン酸化酵素 / ペプチドホルモン / 分泌顆粒 / 糖尿病 / オートクライン / 分泌 / 細胞内輸送 / 細胞増殖 / 細胞内輸

Research Abstract

Phogrin, a member of receptor protein tyrosine phosphatases, primarily localize on secretory granules (SGs) in a variety of neuroendocrine cells including pancreatic β-cells, and recycle between SGs and the plasma membrane upon stimulation of regulated secretion. We suggest that the transitory interaction of phogrin with insulin receptor enables autocrine insulin action in pancreatic β-cells through stabilization of IRS2 protein by inhibition of negative feedback mechanism. We also suggest that phogrin has a supportive role in SG formation, through providing a communication mechanism between the luminal CPE complex and the cytoplasmic transport machinery.

Research Products

• [Journal Article] Multiple sorting systems for secretory granules ensure the regulated secretion of peptide hormones (2013)
  • Author(s): Sun M, Watanabe T, Bochimoto H, Sakai Y, Torii S, Takeuchi T, Hosaka M
  • Journal Title: Traffic Volume: 14 Pages: 205-218
  • NAID: 120005476963
  • Peer Reviewed
• [Journal Article] Immunohistochemical analysis of IA-2 family of protein tyrosine phosphatases in rat gastrointestinal endocrine cells (2013)
  • Author(s): Gomi H, Kubota-Murata C, Yasui T, Tsukise A, Torii S
  • Journal Title: J Histochem Cytochem Volume: 61 Pages: 156-168
  • Peer Reviewed
• [Journal Article] Multiple sorting systems for secretory granules ensure the regulated secretion of peptide hormones. (2013)
  • Author(s): Sun M
  • Journal Title: Traffic Volume: 14 Issue: 2 Pages: 205-218
  • DOI: 10.1111/tra.12029
  • Peer Reviewed
• [Journal Article] Immunohistochemical analysis of IA-2 family of protein tyrosine phosphatases in rat gastrointestinal endocrine cells. (2013)
  • Author(s): Gomi H
  • Journal Title: J Histochem Cytochem Volume: 61 Issue: 2 Pages: 156-168
  • DOI: 10.1369/0022155412466872
  • Peer Reviewed
• [Journal Article] Preferential release of newly synthesized insulin assessed by a multi-label reporter system using pancreatic β-cell line MIN6 (2012)
  • Author(s): Hou N, Mogami H, Kubota-Murata C, Sun M, Takeuchi T, Torii S
  • Journal Title: PLoS One Volume: 7
  • Peer Reviewed
• [Journal Article] Preferential release of newly synthesized insulin assessed by a multi-label reporter system using pancreatic b-cell line MIN6. (2012)
  • Author(s): Hou N
  • Journal Title: PLoS One Volume: 7 Issue: 10 Pages: e47921-e47921
  • DOI: 10.1371/journal.pone.0047921
  • Peer Reviewed
• [Journal Article] Cyclophilin C-associated protein regulation of phagocytic functions via NFAT activation in macrophages (2011)
  • Author(s): Yamaguchi R, Hosaka M, Torii S, Hou N, Saito N, Yoshimoto Y, Imai H, Takeuchi T
  • Journal Title: Brain Res Volume: 1397 Pages: 55-65
  • Peer Reviewed
• [Journal Article] Luminal interaction of phogrin with carboxypeptidase E for effective targeting to secretory granules (2011)
  • Author(s): Saito N, Takeuchi T, Kawano A, Hosaka M, Hou N, Torii S
  • Journal Title: Traffic Volume: 12 Pages: 499-506
  • Peer Reviewed
• [Journal Article] Constitutive reactive oxygen species generation from autophagosome/lysosome in neuronal oxidative toxicity (2010)
  • Author(s): Kubota C, Torii S, Hou N, Saito N, Yoshimoto Y, Imai H, Takeuchi T
  • Journal Title: J Biol Chem Volume: 285 Pages: 667-674
  • Peer Reviewed
• [Journal Article] Constitutive reactive oxygen species generation from autophagosome/lyso some in neuronal oxidative toxicity (2010)
  • Author(s): Kubota C, et al.
  • Journal Title: Journal of Biological Chemistry 285 Pages: 667-674
  • Peer Reviewed
• [Journal Article] Expression and function of IA-2 family proteins,unique neuroendocrine-specific protein-tyrosine phosphatases (2009)
  • Author(s): Torii S
  • Journal Title: Endocrine Journal Volume: 56 Pages: 639-648
  • NAID: 10026914419
  • Peer Reviewed
• [Journal Article] Expression and function of IA-2 family proteins, unique neuroendocrine-specific protein-tyrosine phoaphatases (2009)
  • Author(s): Torii S
  • Journal Title: Endocrine Journal 56 Pages: 639-648
  • Peer Reviewed
• [Presentation] Exocytosis-coupled interaction of insulin receptor and secretory granule-resident PTP phogrin allows for autocrine insulin signaling in pancreatic beta cells (2013)
  • Author(s): Seiji Torii, Naoya Saito, Ayumi Kawano, Ni Hou, Toshiyuki Takeuchi
  • Organizer: 10th International Conference on Protein Phosphatase
  • Place of Presentation: がんセンター(東京)
  • Year and Date: 2013-02-07
• [Presentation] マルチタグ・ラベリング法によるインスリン分泌機構の解析 (2012)
  • Author(s): 鳥居征司、候〓、最上秀夫
  • Organizer: 第30回日本内分泌学会内分泌代謝学サマーセミナー
  • Place of Presentation: 伊香保(群馬)
  • Year and Date: 2012-07-13
• [Presentation] Preferential release of newly generated insulin assessed by a multi-labeling reporter system (2012)
  • Author(s): 鳥居征司、候〓、最上秀夫
  • Organizer: 第64回日本細胞生物学会
  • Place of Presentation: 国際会議場(神戸)
  • Year and Date: 2012-05-29
• [Presentation] Toshiyuki Takeuchi Basal autophagy regulates oxidative stress-associated cell death in neural cells (2011)
  • Author(s): Seiji Torii、Chisato Kubota、Hideaki Imai
  • Organizer: 1st International Symposium on Carcinogenic Spiral and 9th International Conference on Protein Phosphatase
  • Place of Presentation: 東京大学(東京)
  • Year and Date: 2011-02-01
• [Presentation] Basal autophagy regulates oxidative stress-associated cell death in neural cells (2011)
  • Author(s): Seiji Torii, 他3名
  • Organizer: 第9回プロテインホスファターゼ国際カンファレンス
  • Place of Presentation: 東京大学(東京都)
  • Year and Date: 2011-02-01
• [Presentation] Implication of constitutive reactive oxygen species generation from autophagosome/lysosome in neuronal oxidative cell death (2010)
  • Author(s): 鳥居征司、久保田知里、今井英明、竹内利行
  • Organizer: 第62回日本細胞生物学会
  • Place of Presentation: 国際会議場(大阪)
  • Year and Date: 2010-05-20
• [Presentation] オートファゴソーム/リソソーム由来の恒常的ROS産生が酸化ストレス性神経細胞死に関与する (2010)
  • Author(s): 鳥居征司, 他3名
  • Organizer: 第62回日本細胞生物学会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-05-20
• [Presentation] A protein-tyrosine phosphatase phogrin regulates autocrine insulin signaling through direct interaction with insulin receptor (2009)
  • Author(s): Seiji Torii, Naoya Saito, Toshiyuki Takeuchi
  • Organizer: 49th Annual meeting of The American Society for Cell Biology
  • Place of Presentation: San Diego(米国)
  • Year and Date: 2009-12-07
• [Presentation] A protein-tyrosine phophatase phogrin regulates autocrine insulin signaling through direct interaction with insulin receptor (2009)
  • Author(s): 鳥居征司, 他2名
  • Organizer: アメリカ細胞生物学会2009
  • Place of Presentation: San Diego Convention center(米国)
  • Year and Date: 2009-12-07
• [Presentation] 酸化ストレス性神経細胞死に対するオートファジーの関わり (2009)
  • Author(s): 鳥居征司、久保田知里、竹内利行
  • Organizer: 第82回日本生化学会
  • Place of Presentation: 国際会議場(神戸)
  • Year and Date: 2009-10-24
• [Presentation] 酸化ストレス性神経細胞死に対するオートファジーの関わり (2009)
  • Author(s): 鳥居征司, 他2名
  • Organizer: 第82回日本生化学会
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2009-10-24
• [Presentation] 酸化ストレスによる神経細胞死とオートファジー (2009)
  • Author(s): 鳥居征司、久保田知里、竹内利行
  • Organizer: 第8回生体機能研究会
  • Place of Presentation: 箱根(神奈川)
  • Year and Date: 2009-07-25
• [Presentation] Preferential release of newly generated insulin assessed by a multi-labeling reporter system.
  • Author(s): Seiji Torii
  • Organizer: 第64回日本細胞生物学会大会
  • Place of Presentation: 神戸国際会議場（神戸）
• [Presentation] マルチタグ・ラベリング法によるインスリン分泌機構の解析
  • Author(s): 鳥居征司
  • Organizer: 日本内分泌学会 第30回内分泌代謝学サマーセミナー
  • Place of Presentation: 伊香保（群馬）
• [Presentation] 内分泌細胞の分泌顆粒形成におけるグラニンタンパク質の役割
  • Author(s): 穂坂正博
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場（福岡）
• [Book] 膵β細胞におけるphogrin/IA-2の役割 (2010)
  • Author(s): 鳥居征司、竹内利行
  • Publisher: 糖尿病学2010初版 診断と治療社
• [Book] 糖尿病学2010～膵β細胞におけるphogrin/IA2の役割 (2010)
  • Author(s): 鳥居征司、竹内利行
  • Publisher: 診断と治療社