Functional analysis of transcription factor Rfx6 in GIP-producing K-cell

• Project/Area Number: 26860695
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Kyoto University
• Principal Investigator: YAMANE Shunsuke 京都大学, 医学(系)研究科(研究院), 助教 (90582156)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: インクレチン / 肥満 / 肥満症 / GIP

Outline of Final Research Achievements

To investigate the hypothesis that Rfx6 and Rfx3 cooperate with each other and are involved in the regulation of GIP expression in K-cell, we evaluated the effect of knockdown and overexpression of Rfx6 and Rfx3 on GIP gene expression using STC-1 cell line. GIP mRNA expression levels were significantly decreased in Rfx6- knockdown STC-1 cells as we have previously reported. However, Rfx3 knockdown had no effect on GIP gene expression. In addition, simultaneous knockdown of Rfx6 and Rfx3 in STC-1 cells resulted in no change in GIP gene expression compared to single knockdown of Rfx6. Increased GIP expression levels were observed in Rfx6-overexpressiing STC-1 cells and GIP expression levels in Rfx6/Rfx3- overexpressing cells were similar to those in Rfx6-overexpressiing STC-1 cells.

Research Products

• [Journal Article] Control of intestinal stem cell fate: A novel approach to treating diabetes (2016)
  • Author(s): Yamane S, Inagaki N
  • Journal Title: J Diabetes Investig. Volume: 7 Issue: 2 Pages: 166-8
  • DOI: 10.1111/jdi.12390
  • NAID: 120005770741
  • Peer Reviewed / Open Access
• [Journal Article] Enteral supplement enriched with glutamine, fiber, and oligosaccharide modulates incretin and glucagon-like peptide-2 secretion. (2015)
  • Author(s): Joo E., Muraoka A., Hamasaki A., Harada N., Yamane S., Kondo Y., Suzuki K., Nasteska D., Shibue K., Harada T., Iwasaki K., Tsuji H., Shide K., Inagaki N.
  • Journal Title: J Diabetes Investig. Volume: 6 Issue: 3 Pages: 302-308
  • DOI: 10.1111/jdi.12289
  • Peer Reviewed / Open Access
• [Journal Article] Fatty acid binding protein 5 (FABP5) regulates diet-induced obesity (DIO) via GIP secretion from enteroendocrine K-cells in response to fat ingestion. (2015)
  • Author(s): Shibue, K., Yamane, S., Harada, N., Hamasaki, A., Suzuki, K., Joo, E., Iwasaki, K., Nasteska, D., Harada, T., Hayashi, Y., Adachi, Y., Owada, Y., Takayanagi, R. and Inagaki, N.
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 308 Issue: 7 Pages: 583-591
  • DOI: 10.1152/ajpendo.00543.2014
  • Peer Reviewed / Open Access
• [Journal Article] Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K-cells of upper small intestine and has a critical role in GIP secretion after fat ingestion. (2015)
  • Author(s): Iwasaki K, Harada N, Sasaki K, Yamane S, Iida K, Suzuki K, Hamasaki A, Joo E, Nasteska D, Shibue K, Harada T, Hashimoto T, Asakawa Y, Hirasawa A, Inagaki N.
  • Journal Title: Endocrinology Volume: 156 Issue: 3 Pages: 837-837
  • DOI: 10.1210/en.2014-1653
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Inhibition of GIP receptor signaling in adipose tissue reduces insulin resistance and improves hepatic steatosis in high fat diet-induced obesity (2015)
  • Author(s): Erina Joo,Norio Harada, Shunsuke Yamane, Toru Fukushima, Daisuke Taura, Kanako Iwasaki, Akiko Sankoda, Yuki Murata, Kimitaka Shibue, Kazuyo Suzuki, Takanari Harada, Satoko Kuwahara, Yuta Fujiwara, Nobuya Inagaki
  • Organizer: Incretin 2015
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2015-07-31
  • Int'l Joint Research
• [Presentation] Fatty acid-binding protein 5 regulates diet-induced obesity via GIP secretion from enteroendocrine K-cells in response to fat ingestion (2015)
  • Author(s): Kimitaka Shibue,Shunsuke Yamane,Norio Harada, Akihiro Hamasaki, Kazuyo Suzuki, Erina Joo, Kanako Iwasaki, Daniela Nasteska, Takanari Harada, Yoshitaka Hayashi, Yasuhiro Adachi, Yuji Owada, Ryoichi Takayanagi, Nobuya Inagaki
  • Organizer: Incretin 2015
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2015-07-31
  • Int'l Joint Research
• [Presentation] Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K-cells of upper small intestine and has a critical role in GIP secretion after fat ingestion (2015)
  • Author(s): Takanari Harada, Kanako Iwasaki,Norio Harada, Kazuki Sasaki, Shunsuke Yamane, Keiko Iida, Kazuyo Suzuki, Akihiro Hamasaki, Daniela Nasteska, Kimitaka Shibue, Erina Joo,Toshihiro Hashimoto, Yoshinori, Asakawa, Akira Hirasawa, Nobuya Inagaki
  • Organizer: Incretin 2015
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2015-07-31
  • Int'l Joint Research
• [Presentation] Fatty acid-binding protein 5 regulates diet-induced obesity via GIP secretion from enteroendocrine K cells in response to fat ingestion (2015)
  • Author(s): Kimitaka Shibue,Shunsuke Yamane,Norio Harada,Akihiro Hamasaki,Kazuyo Suzuki, Erina Joo, Kanako Iwasaki, Daniela Nasteska, Takanari Harada, Yoshitaka Hayashi, Yasuhiro Adachi, Yuji Owada, Ryoichi Takayanagi, Nobuya Inagaki
  • Organizer: The American Diabetes Association’s 7５th Scientific Sessions
  • Place of Presentation: Boston, MA
  • Year and Date: 2015-06-08
  • Int'l Joint Research
• [Presentation] 脂肪酸受容体ＧＰＲ１２０は上部小腸Ｋ細胞に高発現し脂肪摂取後のＧＩＰ分泌に深く関与する (2015)
  • Author(s): 岩﨑可南子 原田範雄 佐々木香月 山根俊介 飯田桂子 濵崎暁洋 鈴木和代 城尾恵理奈 ナステスカダニエラ 渋江公尊 原田貴成 平澤明 稲垣暢也
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: 下関市
  • Year and Date: 2015-05-21
• [Presentation] 脂肪酸結合タンパク質５（ＦＡＢＰ５）は胆汁の作用を介したＫ細胞における脂肪誘導性ＧＩＰ分泌の制御に関与する (2015)
  • Author(s): 渋江公尊 山根俊介 原田範雄 濱崎暁洋 鈴木和代 城尾恵理奈 岩﨑可南子 ダニエラナステスカ 原田貴成 安達泰弘 大和田祐二 高栁涼一 稲垣暢也
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: 下関市
  • Year and Date: 2015-05-21
• [Presentation] 脂肪酸結合タンパク質５（ＦＡＢＰ５）はＫ細胞における脂肪誘導性ＧＩＰ分泌の制御に関与する (2015)
  • Author(s): 渋江公尊、山根俊介、原田範雄、濱崎暁洋、鈴木和代、城尾恵里奈、岩崎可南子、ダニエラナステスカ、原田貴成、安達泰弘、大和田祐二、高栁涼一、稲垣暢也
  • Organizer: 第29回日本糖尿病・肥満動物学会
  • Place of Presentation: 京都大学医学部芝蘭会館
  • Year and Date: 2015-02-13 – 2015-02-14
• [Presentation] 脂肪酸結合タンパク質５（ＦＡＢＰ５）はＫ細胞における脂肪誘導性ＧＩＰ分泌の制御に関与する (2014)
  • Author(s): 渋江公尊、山根俊介、原田範雄、濱崎暁洋、鈴木和代、城尾恵里奈、岩崎可南子、ダニエラナステスカ、原田貴成、安達泰弘、大和田祐二、高栁涼一、稲垣暢也
  • Organizer: 第26回分子糖尿病学シンポジウム
  • Place of Presentation: 高知市文化プラザ
  • Year and Date: 2014-12-06
• [Presentation] FABP5 is an essential modulator of fatty acid-induced GIP secretion in enteroendocrine K cells (2014)
  • Author(s): Kimitaka Shibue, Shunsuke Yamane, Norio Harada, Akihiro Hamasaki, Kazuyo Suzuki, Erina Joo, Kanako Iwasaki, Daniela Nasteska Takanari Harada, Yasuhiro Adachi, Yuji Owada, Ryoichi Takayanagi, Nobuya Inagaki
  • Organizer: 50th EASD Annual Meeting
  • Place of Presentation: Wien, Austria
  • Year and Date: 2014-09-16 – 2014-09-19