Physiological substrate of beta cell autophagy

• Project/Area Number: 23390244
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Juntendo University
• Principal Investigator: WATADA Hirotaka 順天堂大学, 医学部, 教授 (60343480)
• Co-Investigator(Kenkyū-buntansha): FUJITANI Yoshio 順天堂大学, 医学部, 先任准教授 (30433783)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000); Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2012: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2011: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: 膵β細胞 / オートファジー / インスリン / アポトーシス / アミリン / 糖脂質代謝 / アミロイド / 糖尿病

Research Abstract

Type2 diabetes mellitus is a serious health problem in the world. In this study, to uncover the pathophisiology of beta cells observed in type 2 diabetes mellitus, we investigated the role of autophagy failure on the human islet amyloid polypeptide (hIAPP) toxicity. Detailed analyses using knock-out mices revealed that autophagy failure deteriorats beta cell toxicity of hIAPP under insulin resistance condition. These data suggest that autophagy failure may be involved in the pathogenesis of beta cell failure in type 2 diabetes.

Research Products

• [Journal Article] Human IAPP-induced pancreatic beta-cell toxicity and its regulation by autophagy (2014)
  • Author(s): Shigihara N., Fukunaka A., Hara A., Komiya K., Honda A., Uchida T., Abe H., Toyofuku Y., Tamaki M., Ogihara T., Miyatsuka T., Hiddinga HJ, Sakagashira S, Koike M., Uchiyama Y., Yoshimori T., Eberhardt NL, Fujitani Y., Watada H
  • Journal Title: J. Clin. Invest Volume: (in press)
• [Journal Article] Exendin-4 improves beta-cell function in autophagy-deficient beta-cells (2013)
  • Author(s): Abe H, Uchida T, Hara A, Mizukami H, Komiya K, Koike M, Shigihara N, Toyofuku Y, Ogihara T, Uchiyama Y, Yagihashi S, Fujitani Y, Watada H
  • Journal Title: Endocrinology Volume: 154 Pages: 4512-4524
• [Journal Article] Exendin-4 improves β-cell function in autophagy-deficient β-cells. (2013)
  • Author(s): Abe H, Uchida T, Hara A, Mizukami H, Komiya K, Koike M, Shigihara N, Toyofuku
  • Journal Title: Endocrinology Volume: 154 Issue: 12 Pages: 4512-24
  • DOI: 10.1210/en.2013-1578
  • Peer Reviewed
• [Presentation] ERp57 protects autophagy deficient beta-cells from cellular damage (2013)
  • Author(s): Yamamoto E, Uchida T, Abe H, Komiya K, Hara A, Ogihara T, Takeda S, Fujitani Y, Watada H
  • Organizer: American Diabetes Association 73rd Scientific Sessions
  • Place of Presentation: Chicago (America)
• [Presentation] ERp57はオートファジー不全に伴う膵β細胞障害に保護的に作用する (2013)
  • Author(s): 山本恵理子, 内田 豊義, 阿部浩子, 小宮幸次, 原朱美, 荻原健, 武田 省, 藤谷与士夫, 綿田裕孝
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本県(日本)
• [Presentation] 膵β細胞特異的オートファジー欠損マウスにおいて, エキセナチドは耐糖能と膵β細胞機能を改善する (2013)
  • Author(s): 阿部浩子, 内田豊義, 原朱美, 水上浩哉, 小宮幸次, 小池正人, 内山安男, 八木橋操六, 藤谷与士夫, 綿田裕孝
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 宮城県(日本)
• [Presentation] Exendin-4 treatment improves glucose and beta-cell function of beta-cell-specific autophagy deficient mice (2012)
  • Author(s): Abe H, Uchida T, Komiya K, Shigihara N, Toyofuku Y, Hara A, Hirose T, Fujitani Y, Watada H
  • Organizer: American Diabetes Association 72nd Scientific Sessions
  • Place of Presentation: Philadelphia (America)
• [Presentation] 膵β細胞特異的オートファジー欠損マウスにおいて, エキセナチドは耐糖能と膵β細胞機能を改善する (2012)
  • Author(s): 阿部浩子, 内田豊義, 小宮幸次, 鴫原奈弓, 豊福優希子, 原朱美, 弘世貴久, 藤谷与士夫, 綿田裕孝
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 神奈川県(日本)
• [Presentation] 糖尿病とオートファジー (2012)
  • Author(s): 藤谷与士夫
  • Organizer: 第17回東京肝臓シンポジウム
  • Place of Presentation: 東京都(日本)
• [Presentation] 膵β細胞におけるオートファジーの意義 (2012)
  • Author(s): 綿田裕孝
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 愛知県(日本)
• [Presentation] Autophagy in the beta cells (2011)
  • Author(s): Watada H
  • Organizer: The 16th Japan-Korea Symposium on Diabetes Mellitus
  • Place of Presentation: Tokyo (Japan)
  • Year and Date: 2011-10-21
• [Presentation] Autophagy and Quality Control in the Beta CellQuality Control in the Beta Cell. Nutrient Control over Autophagy in the Beta Cell (2011)
  • Author(s): Watada H
  • Organizer: American Diabetes Association 71st scientific sessions
  • Place of Presentation: San Diego (America)
• [Presentation] 膵β細胞特異的Atg7欠損マウスに対するExenatide作用の検討 (2011)
  • Author(s): 阿部浩子, 内田豊義, 鴫原奈弓, 小宮幸次, 豊福優希子, 弘世貴久, 藤谷与士夫, 綿田裕孝
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 北海道(日本)
• [Presentation] 膵β細胞において, 遊離脂肪酸投与による急性期のオートファジー活性化は小胞体ストレスを介さずに誘導される (2011)
  • Author(s): 小宮幸次, 内田豊義, 阿部浩子, 田蒔基行, 河盛隆造, 弘世貴久, 藤谷与士夫, 綿田裕孝
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 北海道(日本)
• [Presentation] 膵β細胞における遊離脂肪酸誘導性オートファジーのメカニズム解析 (2011)
  • Author(s): 小宮幸次, 内田豊義, 阿部浩子, 河盛隆造, 藤谷与士夫 , 綿田裕孝
  • Organizer: 第84回日本内分泌学会学術総会
  • Place of Presentation: 兵庫県(日本)
• [Remarks]
  • URL: http://www.juntendo.ac.jp/graduate/laboratory/labo/taisya_naibunpitsu/