The functional significance of cAMP compartment in cAMP-regulated exocytosis

• Project/Area Number: 18790203
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Kobe University
• Principal Investigator: SHIBASAKI Tadao Kobe University, 大学院医学研究科, 講師 (00323436)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,610,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
• Keywords: インスリン分泌 / 糖尿病 / インスリン分泌顆粒 / 膵β細胞 / バイオイメージング / 全反射型蛍光顕微鏡 / インスリン分必顆粒

Research Abstract

膵β細胞においてcAMP シグナルは、インスリン顆粒の細胞内から細胞膜へのリクルートメントと細胞膜への融合を促進することでインスリン分泌を増強することが明らかになった。
またcAMP センサーEpac2 は細胞膜近傍のインスリン顆粒プールのサイズを増やすことでインスリン分泌増強の第1相を担っていた。
さらにこのようなEpac2 の機能には、Epac2 の細胞膜への局在が必要であったことから、細胞膜近くに存在するcAMP つまり、cAMP compartment がEpac2を介したインスリン分泌増強に重要であることが示された。

Research Products

• [Journal Article] Critical role of the N-terminal cyclic AMP-binding domain of Epac2 in its subcellular localization and function (2009)
  • Author(s): Niimura M. Miki T, Shibasaki T, Fujimoto W, Iwanaga T, and Seino S
  • Journal Title: J Cell Physiol 219 Pages: 652-658
  • Peer Reviewed
• [Journal Article] Rab11 and its effector Rip11 participate in regulation of Insulin granule exocytosis (2009)
  • Author(s): Sugawara K, Shibasaki T, Mizoguchi A, Saito T, and Seino S
  • Journal Title: Genes to Cells 14 Pages: 445-465
  • Peer Reviewed
• [Journal Article] Involvement of Exoc3l, a protein structurally related to the exocyst subunit Sec6, in insulin secretion (2008)
  • Author(s): Saito T, Shibasaki T, and Seino S
  • Journal Title: Biomed Res 29 Pages: 85-91
  • NAID: 130004724053
  • Peer Reviewed
• [Journal Article] インスリン顆粒動態シミュレーターの開発Simulation of insulin granules dynamics(シミュレーションによるインスリン分泌の可視化) (2008)
  • Author(s): 須永泰弘、柴崎忠雄、高橋晴美、川原康弘、福島光、清野 進
  • Journal Title: 糖尿病診療マスター、医学書院 第6巻 第4号 Pages: 453-455
• [Journal Article] cAMP によるインスリン開口分泌の制御 (2008)
  • Author(s): 柴崎忠雄、高橋晴美、清野 進
  • Journal Title: 糖尿病学の進歩 第42集 Pages: 6-9
• [Journal Article] Involvement of Exoc31, a protein structurally related to the exocyst subunit Sec6, in insulin secretion (2008)
  • Author(s): Saito, T., et.al.
  • Journal Title: Biomed Res 29 Pages: 85-91
  • Peer Reviewed
• [Journal Article] インスリン顆粒動態シミュレーターの開発 (2008)
  • Author(s): 須永泰弘, 他
  • Journal Title: 糖尿病診療マスター 6 Pages: 453-455
• [Journal Article] Essential role of Epac2/Rap1 signaling in regulation of insulin granule dynamics by cAMP (2007)
  • Author(s): Shibasaki T, Takahashi H, Miki T, Sunaga Y, Matsumura K, Yamanaka M, Zhang C, Tamamoto A, Satoh T, Miyazaki J, and Seino S
  • Journal Title: Proc Natl Acad Sci USA 104 Pages: 19333-19338
  • Peer Reviewed
• [Journal Article] Essential role of Epac2/Rapl signaling in regulation of insulin granule dynamics by cAMP. (2007)
  • Author(s): Shibasaki, T, et. al.
  • Journal Title: Proc Natl Acad Sci USA 104 Pages: 19333-19338
  • Peer Reviewed
• [Journal Article] Pancreatic beta cell (2007)
  • Author(s): Seino, S, et. al. (分担執筆)
  • Journal Title: Pancreatic beta cell in health and disease 編者名: Seino, S and Bell, G (PKA-independent mechanism of cAMP in insulin secretion), Springer Pages: 133-146
• [Journal Article] cAMP シグナルによるエキソサイトーシスの調節機構 (2006)
  • Author(s): 柴崎忠雄、清野 進
  • Journal Title: 生体の科学、医学書院 第57 巻2 号 Pages: 91-96
• [Journal Article] cAMP コンパートメントとインスリン分泌 分子糖尿病学の進歩 (2006)
  • Author(s): 柴崎忠雄、清野 進
  • Journal Title: 基礎から臨床まで-2006、金原出版 Pages: 2-7
• [Journal Article] Identification and characterization of a novel member of the ATP-sensitive K^+ channel subunit family, Kir6.3, in zebrafish (2006)
  • Author(s): Zhang C et al.
  • Journal Title: Physiol Genomics 24・3 Pages: 290-297
• [Journal Article] cAMPシグナルによるエキソサイトーシスの調節機構 (2006)
  • Author(s): 柴崎忠雄
  • Journal Title: 生体の科学 57 Pages: 91-96
• [Journal Article] cAMPコンパートメントとインスリン分泌 (2006)
  • Author(s): 柴崎忠雄
  • Journal Title: 分子糖尿病学の進歩 基礎から臨床まで-2006 Pages: 2-7
• [Journal Article] Regulation of insulin granule exocytosis: diverse roles of cAMP signaling
  • Author(s): Seino S, Takahashi H, Fujimoto W, and Shibasaki T
  • Journal Title: Diabetes Obesity, and Metabolism
  • Peer Reviewed
• [Journal Article] Critical role of the N-terminal cyclic AMP-binding domain of Epac2 in its subcellular localization and function
  • Author(s): Niimura M., et.al.
  • Journal Title: J Cell Physiol (In press)
  • Peer Reviewed
• [Journal Article] Rabli and its effector Rip11 participate in regulation of Insulin granule exocytosis
  • Author(s): Sugawara K., et.al.
  • Journal Title: Genes to Cells (In press)
  • Peer Reviewed
• [Journal Article] Involvement of Exoc31, a protein structurally related to the exocyst subunit Sec6, in insulin secretion.
  • Author(s): Saito, T., et. al.
  • Journal Title: Biomed Res (印刷中)
  • Peer Reviewed
• [Presentation] インスリン開口分泌のダイナミクス (2009)
  • Author(s): 柴崎忠雄, 他
  • Organizer: 第43回糖尿病学の進歩・レクチャー
  • Place of Presentation: 松本
  • Year and Date: 2009-02-20
• [Presentation] Development of a full-length Epac2 FRET sensor and its application (2008)
  • Author(s): Katoh M, Zhang C-L, Shibasaki T, and Seino S
  • Organizer: 44th Annual Meeting, The American Society for Cell Biology(ポスター)
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2008-12-13
• [Presentation] インスリン顆粒の開口放出機構におけるRim2 の重要性 (2008)
  • Author(s): 安田貴雄、柴崎忠雄、三木隆司、高橋晴美、宮崎純一、南幸太郎、清野 進
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(ポスター)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] 膵β細胞の代謝調節とインスリン分泌 (2008)
  • Author(s): 清野 進、柴崎忠雄、岩崎真宏、南幸太郎
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(シンポジウム)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] Both the first and second phases of glucose-induced insulin secretion involve insulin granules newly recruited to the plasma membrane (2008)
  • Author(s): Takahashi H, Shibasaki T, and Seino S
  • Organizer: 44th Annual Meeting of the European Association for the Study of Diabetes
  • Place of Presentation: Rome, Italy
  • Year and Date: 2008-09-09
• [Presentation] Critical role of Rim2 in insulin granule exocytosis (2008)
  • Author(s): 安田貴雄、南幸太郎、柴崎忠雄、高橋晴美、宮崎純一、三木隆司、清野 進
  • Organizer: 第60 回日本細胞生物学会大会(ポスター)
  • Place of Presentation: 横浜
  • Year and Date: 2008-06-30
• [Presentation] Dynamics of Insulin Granules, The 6th Catholic International Stem Cell Symposium (2008)
  • Author(s): Shibasaki T, Takahashi H, Miki T, and Seino S
  • Organizer: The 3rd Korea-Japan Islet Club Meeting(シンポジウム)
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2008-06-20
• [Presentation] Dynamics of Insulin Granules (2008)
  • Author(s): Shibasaki T, 他
  • Organizer: The 6th Catholic International Stem Cell Symposium, The 3rd Korea-Japan Islet Club Meeting・シンポジウム
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2008-06-20
• [Presentation] Critical role of Rim2 in insulin granule exocytosis. 68th Scientific Sessions (2008)
  • Author(s): Yasuda T, Shibasaki T, Miki T, Takahashi H, Miyazaki J, Minami K, and Seino S
  • Organizer: American Diabetes Association(ポスター)
  • Place of Presentation: SanFrancisco, USA
  • Year and Date: 2008-06-07
• [Presentation] Roles of Exocytosis-associated Proteins in Pancreatic Beta-cells (2008)
  • Author(s): Seino S, Takahashi H, Miki T, and Shibasaki T
  • Organizer: Keystone Symposia: Islet and Beta Cell Biology(シンポジウム)
  • Place of Presentation: Snowbird, USA
  • Year and Date: 2008-04-09
• [Presentation] Roles of Exocytosis-associated Proteins in Pancreatic Beta-cells (2008)
  • Author(s): Shibasaki T, 他
  • Organizer: Keystone Symposia : Islet and Beta Cell Biology・シンポジウム
  • Place of Presentation: Snowbird, USA
  • Year and Date: 2008-04-09
• [Presentation] インスリン開口分泌の制御 (2008)
  • Author(s): 柴崎忠雄 高橋晴美 清野 進
  • Organizer: 第43回糖尿病学の進歩(レクチャー)
  • Place of Presentation: 松本
  • Year and Date: 2008-02-20
• [Presentation] cAMPによるインスリン開口分泌の制御 (2008)
  • Author(s): 柴崎忠雄、高橋晴美、清野 進
  • Organizer: 第42回糖尿病学の進歩(レクチャー)
  • Place of Presentation: 高松
  • Year and Date: 2008-02-15
• [Presentation] cAMPによるインスリン開口分泌の制御 (2008)
  • Author(s): 柴崎忠雄, 他
  • Organizer: 第42回糖尿病学の進歩・レクチャー
  • Place of Presentation: 高松
  • Year and Date: 2008-02-15
• [Presentation] cAMPによるインスリン開口分泌の制御 (2007)
  • Author(s): 柴崎忠雄、高橋晴美、清野 進
  • Organizer: 第50日本糖尿病学会年次集会(シンポジウム)
  • Place of Presentation: 仙台
  • Year and Date: 2007-05-25
• [Presentation] cAMPによる開口分泌制御 (2007)
  • Author(s): 柴崎忠雄, 他
  • Organizer: 第50回日本糖尿病学会年次学術集会・シンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2007-05-25
• [Book] Seino S and Bell GI (eds.) Springer (2008)
  • Author(s): Seino S, Miki T, and Shibasaki T
  • Publisher: PKA-independent mechanism of cAMP in insulin secretion. Pancreatic Beta Cell in Health and Disease
• [Book] 糖尿病学の進歩第42集日本糖尿病学会編(タイトル : cAMPによるインスリン開口分泌の制御) (2008)
  • Author(s): 柴崎忠雄, 他(分担執筆)
  • Publisher: 診断と治療社