Development of induction method of insulin-producing cells in vivo

• Project/Area Number: 16K14588
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science
• Research Institution: University of Tsukuba
• Principal Investigator: TAKAHASHI Satoru 筑波大学, 医学医療系, 教授 (50271896)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: インシュリン / β細胞 / 再生 / 転写因子 / 肝細胞 / インスリン / 肝臓細胞

Outline of Final Research Achievements

To search for new factors that promote conversion to insulin-producing cells from liver cells, Mouse insulin promoter 1-GFP transgenic mouse (MIP-GFP Tg), which has GFP reporter regulated by mouse insulin promoter was used. After isolating insulin producing cells, we did microarray analysis for identifing genes that are expressed in normal β cells, but not in induced insulin producing cells. As a result, new candidate genes Isl1β and Efl3 were identified. Each candidate gene was examined to confirm cooperative action in insulin production with Pdx1, NeuroD, MafA in vivo. Coexpression of Isl1β enhanced insulin production from liver cells by about 10 times. On the other hand, coexpression of Efl3 revealed that insulin transcription was suppressed contrary to expectation.
From the above results, it has been confirmed that Isl1β, together with Pdx1, NeuroD, MafA, has an effect of enhancing the production of insulin from liver cells. These results were published in Endocrinology.

Research Products

• [Journal Article] Isl1β Overexpression With Key β Cell Transcription Factors Enhances Glucose-Responsive Hepatic Insulin Production and Secretion (2017)
  • Author(s): Jung Yunshin、Zhou Ruyi、Kato Toshiki、Usui Jeffrey K、Muratani Masafumi、Oishi Hisashi、Heck Margarete M S、Takahashi Satoru
  • Journal Title: Endocrinology Volume: 159 Pages: 869-882
  • DOI: 10.1210/en.2017-00663
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Generation of CRISPR/Cas9-mediated bicistronic knock-in <i>ins1-cre</i> driver mice (2016)
  • Author(s): Yoshikazu Hasegawa, Yoshikazu Hoshino, Abdelaziz E. Ibrahim, Kanako Kato, Yoko Daitoku1, Yoko Tanimoto, Yoshihisa Ikeda, Hisashi Oishi, Satoru Takahashi, Atsushi Yoshiki, Ken-ichi Yagami, Hiroyoshi Iseki, Seiya Mizuno, Fumihiro Sugiyama
  • Journal Title: Exp. Anim. Volume: 65 Issue: 3 Pages: 319-27
  • DOI: 10.1538/expanim.16-0016
  • NAID: 130006882371
  • ISSN: 1341-1357, 1881-7122
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Remarks] 筑波大学 医学医療系 解剖学・発生学研究室
  • URL: http://www.md.tsukuba.ac.jp/basic-med/anatomy/embryology/index.html
• [Remarks] 筑波大学 医学医療系 解剖学・発生学研究室ホームページ
  • URL: http://www.md.tsukuba.ac.jp/basic-med/anatomy/embryology/index.html
• [Remarks] 筑波大学 生命科学動物資源センター ホームページ
  • URL: http://www.md.tsukuba.ac.jp/LabAnimalResCNT/