The molecular mechanisms of transcriptional and translational control of stress responses in pancreatic β cells

• Project/Area Number: 19590300
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Nihon University (2008); Tohoku University (2007)
• Principal Investigator: ISHIHARA Hisamitsu Nihon University, 医学部, 医学部 (60361086)
• Co-Investigator(Kenkyū-buntansha): YAMAGUCHI Suguru 東北大学, 国際高等融合領域研究所, 助教授 (70451614)
• Co-Investigator(Renkei-kenkyūsha): YAMAGUCHI Suguru 東北大学, 国際高等融合領域研究所, 助教授 (70451614)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 糖尿病 / 膵島 / シグナル伝達

Research Abstract

膵β細胞において翻訳(タンパク合成)抑制因子4E-BP1が、ストレス応答のマスター転写因子であるATF4の活性化によって発現増加することを明らかにした。また、4E-BP1欠損マウスβ細胞は、小胞体ストレスに対し脆弱になっていることを突き止めた。これらのことから、小胞体ストレス下のβ細胞では、タンパク合成を抑制しておくことが生存にとっては利であり、そのために4E-BP1の発現が誘導されるものと考えられた。

Research Products

• [Journal Article] Carotid arterial elasticity is a sensitive atherosclerosis valuereflecting visceral fat accumulation in obese subjects. (2009)
  • Author(s): Ai Tokita
  • Journal Title: Atherosclerosis (In press)
  • Peer Reviewed
• [Journal Article] Minokoshi Y, Oka Y. Regulation of Pancreatic β cell Mass by Neuronal Signals from the Liver (2008)
  • Author(s): Imai J, Katagiri H, Yamada T, Ishigaki Y, Suzuki T, Kudo H, Uno K, Hasegawa Y, Gao J, Kaneko K, Ishihara H, Niijima A, Nakazato M, Asano T
  • Journal Title: Science 322 Pages: 1250-1254
  • Peer Reviewed
• [Journal Article] ATF4-mediated induction of 4E-BP1 contributes to pancreatic β cell survival under endoplasmic reticulum stress (2008)
  • Author(s): Yamaguchi S, Ishihara H, Yamada T, Tamura A, Usui M, Tominaga R, Munakata Y, Satake C, Katagiri H, Tashiro F, Aburatani H, Tsukiyama-Kohara K, Miyazaki J, Sonenberg N, Oka Y
  • Journal Title: Cell Metab 7 Pages: 269-276
  • Peer Reviewed
• [Journal Article] The GDP-dependent Rab27aeffector coronin 3 controls endocytosis of seceratry membrane in insulin secreting cell lines (2008)
  • Author(s): Kimura T, Kaneko Y, Yamada S, Ishihara H, Senda T, Iwamatsu A, Niki I
  • Journal Title: J Cell Sci 121 Pages: 3092-3098
  • Peer Reviewed
• [Journal Article] Impact of plasma oxidized low-density lipoprotein removal on atherosclerosis (2008)
  • Author(s): Ishigaki Y, Katagiri H, Gao J, Yamada T, Imai J, Hasegawa Y, Kaneko K, Ogihara T, Ishihara H, Sata Y, Takikawa K, Nishimichi N, Matsuda, H., Sawamura, T., Oka, Y
  • Journal Title: Circulation 118 Pages: 75-83
  • Peer Reviewed
• [Journal Article] Behavioral and gene expression analyses of Wfs1 knockout mice as a possible animal model of mood disorder (2008)
  • Author(s): Kato T, Ishiwata M, Yamada K, Kasahara T, Kakiuchi C, Iwamoto K, Kawamura K, Ishihara H, Oka Y
  • Journal Title: Neurosci Res 61 Pages: 143-158
  • Peer Reviewed
• [Journal Article] Regulation of pancreatic beta cell mass by neuronal signals from the liver. (2008)
  • Author(s): Junta Imai
  • Journal Title: Science 322 Pages: 1250-1254
  • Peer Reviewed
• [Journal Article] Regulation of pancreatic beta cell mass by neuronal signals from the liver. (2008)
  • Author(s): Yasushi Ishigaki
  • Journal Title: Circulation 118 Pages: 75-83
  • Peer Reviewed
• [Journal Article] The GDP-dependent Rab27a effector coronin 3 controls endocytosis of secretory membrane in insulin-secreting cell lines. (2008)
  • Author(s): Toshihide Kimura
  • Journal Title: J. Cell Science 121 Pages: 3092-3098
  • Peer Reviewed
• [Journal Article] ATF4-mediated induction of 4E-BP1 contributes to pancreatic β cell survival under endoplasmic reticulum stress (2008)
  • Author(s): 山口賢, 石原寿光, 山田高広, 田村明, 薄井正寛, 富永竜, 宗像佑一郎, 佐竹千尋, 片桐秀樹, 田代文, 油谷浩幸, 小原恭子, 宮崎純一, Nahum Sonenberg, 岡芳知
  • Journal Title: Cell Metabolism 7 Pages: 269-276
  • Peer Reviewed
• [Journal Article] Behavioral and gene expression analyses of Wfs1 knockout mice as a possible animal model of mood disorder (2008)
  • Author(s): 加藤忠文, 石渡みずほ, 山田一之, 笠原和起, 垣内千尋, 岩本和也, 河村光毅, 石原寿光, 岡芳知
  • Journal Title: Neuroscience Research (印刷中)
  • Peer Reviewed
• [Journal Article] The conserved carboxyl terminus of human parainfluenza virus type 2 V protein plays an important role in virus growth (2007)
  • Author(s): Nishio M, Tsurudome M, Ishihara H, Ito M, Ito Y
  • Journal Title: Virology 362 Pages: 85-98
  • Peer Reviewed
• [Journal Article] Bone marrow (BM) transplantation promotes β-cell regeneration after acute injury through BM cell mobilization (2007)
  • Author(s): Hasegawa Y, Ogihara T, Yamada T, Ishigaki Y, Imai J, Uno K, Gao J, Kaneko K, Ishihara H, Sasano H, Nakauchi H, Oka Y, Katagiri H
  • Journal Title: Endocrinology 148 Pages: 2006-2015
  • Peer Reviewed
• [Journal Article] Bone marrow(BM)transplantation promotes β cell regeneration after acute injury through BM cell mobilization (2007)
  • Author(s): 長谷川豊, 荻原健英, 山田哲也, 石垣泰, 今井淳太, 宇野健司, 高俊文, 金子慶三, 石原寿光, 笹野公伸, 中内拓光, 岡芳知, 片桐秀樹
  • Journal Title: Endocrinology 148 Pages: 2006-2015
  • Peer Reviewed
• [Journal Article] Carotid arterial elasticity is a sensitive atherosclerosis value reflecting visceral fat accumulation in obese subjects
  • Author(s): Tokita A, Ishigaki Y, Okimoto H, Hasegawa H, Koiwa Y, Kato M, Ishihara H, Hinokio Y, Katagiri H, Kanai H, Oka Y
  • Journal Title: Atherosclerosis (in press)
  • Peer Reviewed
• [Presentation] 膵β細胞量調節とストレス応答 (2009)
  • Author(s): 石原寿光
  • Organizer: 第43回糖尿病学の進歩
  • Place of Presentation: 松本市
  • Year and Date: 2009-02-20
• [Presentation] Essential role of translational control in β cell survival under stress conditions (2008)
  • Author(s): Ishihara H
  • Organizer: Asia Islet Biology & Incretin Symposium
  • Place of Presentation: Incheon, Korea
  • Year and Date: 2008-10-18
• [Presentation] 膵β細胞量の調節におけるmRNA 翻訳制御の役割 (2008)
  • Author(s): 石原寿光、山口賢、薄井正寛、冨永竜、岡芳知
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-24
• [Presentation] 翻訳抑制因子4E-BP1は、慢性的な小胞体ストレス下の膵β細胞において翻訳抑制を介して細胞を保護する (2008)
  • Author(s): 山口賢、石原寿光、田村明、山田高弘、冨永竜、宗像佑一郎、檜尾好徳、荻原健英、鈴木進、片桐秀樹、岡芳知
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-24
• [Presentation] 膵β細胞における小胞体ストレス応答と酸化ストレス応答の特徴 (2008)
  • Author(s): 富永竜、石原寿光、山田高弘、山口賢、宗像佑一郎、檜尾好徳、荻原健英、鈴木進、片桐秀樹、岡芳知
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-24
• [Presentation] 翻訳抑制因子4E-BP1は小胞体ストレス応答転写因子ATF4の直接のターゲットである (2008)
  • Author(s): 佐竹千尋、石原寿光、田村明、山田高弘山口賢、冨永竜、宗像佑一郎、檜尾好徳、荻原健英、鈴木進、片桐秀樹、岡芳知
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-24
• [Presentation] 膵β細胞小胞体ストレス応答における翻訳抑制因子4E-BP1の役割 (2008)
  • Author(s): 石原寿光、山田高弘、山口賢、冨永竜、宗像佑一郎、檜尾好徳、荻原健英、鈴木進、片桐秀樹、岡芳知
  • Organizer: 第81回日本内分泌学会学術集会
  • Place of Presentation: 青森市
  • Year and Date: 2008-05-16
• [Presentation] 膵β細胞小胞体ストレス応答における翻訳抑制因子4E-BP1の役割 (2008)
  • Author(s): 石原 寿光
  • Organizer: 第81回 日本内分泌学会学術総会
  • Place of Presentation: 青森市
  • Year and Date: 2008-05-16
• [Presentation] 2型糖尿病の発症における膵β細胞障害 (2008)
  • Author(s): 石原寿光
  • Organizer: 第42回糖尿病学の進歩
  • Place of Presentation: 高松市
  • Year and Date: 2008-02-15
• [Presentation] Transcription factor TFII-I binds to WFS1 protein and dissociates in response to endoplasmic reticulum stress (2007)
  • Author(s): Yamaguchi S, Ishihara H, Oka Y
  • Organizer: The 67th scientific sessions of American Diabetes Association
  • Place of Presentation: Chicago
  • Year and Date: 2007-06-23
• [Presentation] Transcription factor TFII-I binds to WFS1 protein and dissociates in response to endoplasmic reticulum stress. (2007)
  • Author(s): 山口賢, 石原寿光, 岡芳知
  • Organizer: The 67th scientific sessions of American Diabetes Association
  • Place of Presentation: Chicago
  • Year and Date: 2007-06-23
• [Presentation] 翻訳抑制因子4E-BP1の欠損は小胞体ストレスによる膵β細胞障害を悪化させる (2007)
  • Author(s): 山口賢、石原寿光、田村明、山田高弘、佐竹千尋、薄井正寛、冨永竜、檜尾好徳、荻原健英、鈴木進、片桐秀樹、岡芳知
  • Organizer: 第50回日本糖尿病学会年次学術集会
  • Place of Presentation: 仙台市
  • Year and Date: 2007-05-25
• [Presentation] 膵β細胞特異的小胞体ストレス応答の検討 (2007)
  • Author(s): 宗像佑一郎、石原寿光、田村明、山田高弘、山口賢、佐竹千尋、薄井正寛、冨永竜、檜尾好徳、荻原健英、片桐秀樹、岡芳知
  • Organizer: 第50回日本糖尿病学会年次学術集会
  • Place of Presentation: 仙台市
  • Year and Date: 2007-05-25
• [Presentation] An essential role of the translational suppressor 4E-BP1 in pancreatic β cell survival under ER stress (2007)
  • Author(s): Ishihara H
  • Organizer: 日本糖尿病学会年次学術集会
  • Place of Presentation: 仙台市
  • Year and Date: 2007-05-25
• [Presentation] 翻訳抑制因子4E-BP1の欠損は、小胞体ストレスによる膵β細胞障害を悪化させる (2007)
  • Author(s): 山口賢, 石原寿光, 田村明, 山田高弘, 佐竹千尋, 薄井正寛, 冨永竜, 檜尾好徳, 荻原健英, 鈴木進, 片桐秀樹, 岡芳知
  • Organizer: 第50回日本糖尿病学会年次学術集会
  • Place of Presentation: 仙台市
  • Year and Date: 2007-05-25
• [Presentation] 膵β細胞における小胞体ストレスによる翻訳抑制因子4E-BP1発現誘導機構 (2007)
  • Author(s): 薄井正寛、佐竹千尋、石原寿光、田村明、山田高弘、山口賢、冨永竜、宗像佑一郎、檜尾好徳、荻原健英、鈴木進、片桐秀樹、岡芳知
  • Organizer: 第50回日本糖尿病学会年次学術集会
  • Place of Presentation: 仙台市
  • Year and Date: 2007-05-24
• [Book] WFS1 Protein (wolframin): Emerging Link between the Emotional Brain and Endocrine Pancreas. (Chapter 2. Progressive β cell loss and defective) (Koks and Vasar ed.) (2009)
  • Author(s): Ishihara H, Takeda S, Tamura A, Takahashi R, Yamaguchi S, Takei D, Yamada T, Inoue H, Tanizawa Y, Oka Y
  • Publisher: Research Signpost
• [Book] WFS1 Protein (wolframin): Emerging Link between the Emotional Brain and Endocrine Pancreas. (Chapter 3. Role of endoplasmic reticulum stress in pancreatic β cell loss in WFS1-deficient mice) (Koks and Vasar ed.) (2009)
  • Author(s): Ishihara H, Yamaguchi S, Yamada T, Tamura A, Oka Y
  • Publisher: Research Signpost
• [Book] WFS1 Protein(wolframin) : Emerging Link between the Emotional Brain and Endocrine Pancreas (2009)
  • Author(s): 石原 寿光
  • Publisher: WFS1 Protein(wolframin) : Emerging Link between the Enotional Brain and Endocrine pancreas
• [Remarks]
  • URL: http://www.hosp.tohoku.ac.jp/gakujyutu/g05_tounyou.html
• [Remarks]
  • URL: http://www.med.nihon-u.ac.jp/department/dmet/
• [Remarks]
  • URL: http://www.med.nihon-u.ac.jp/departraent/dmet/
• [Remarks]
  • URL: http://www.hosp.tohoku.ac.jp/gakujyutu/g05_tounyou.html