Challenge for diabetes therapy based on understanding of stress signals in pancreatic islet niche

• Project/Area Number: 25860759
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Sasaki Foundation
• Principal Investigator: Okita Naoyuki 公益財団法人佐々木研究所, 附属佐々木研究所, 研究員 (60453841)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 膵島 / ストレス応答 / 2型糖尿病 / 膵島ニッチ / 膵島傷害 / 膵島障害

Outline of Final Research Achievements

Decline of pancreatic islet homeosotatsis by nutrient stress is involved in the pathogenesis of type2 diabetes mellitus. In the present study, I established the research basis for understanding the signal network of pancreatic islet failure focused on cell-cell interaction. I obtained the results as shown below: difference among chronic nutrient stresses in beta cell line: optimization of pseudoislet formation: construction of plasmid vectors that possess tetracylin-dependent gene regulatory system with cell marking system by fluorescence proteins: improved method of western blotting for Insulin and the other diabetes-associated peptide hormones.

Research Products

• [Journal Article] Chronological analysis of caloric restriction-induced alteration of fatty acid biosynthesis in white adipose tissue of rats. (2015)
  • Author(s): Naoyuki Okita, Takuro Tsuchiya, Mayumi Fukushima, Kaho Itakura, Keiko Yuguchi, Takumi Narita, Yukari Hashizume, Yuka Sudo, Takuya Chiba, Isao Shimokawa, Yoshikazu Higami,
  • Journal Title: EXPERIMENTAL GERONTOLOGY Volume: 63 Pages: 59-66
  • DOI: 10.1016/j.exger.2015.01.043
  • Peer Reviewed / Open Access
• [Journal Article] Poly(ADP-ribose) Polymerase Inhibitor (PJ34) Reduces Pulmonary Ischemia-Reperfusion Injury in Rats (2014)
  • Author(s): Hatachi G, Tsuchiya T, Miyazaki T, Matsumoto K, Yamasaki N, Okita N, Nagashima A, Higami Y, Nagayasu T
  • Journal Title: Transplantation Volume: 98 Issue: 6 Pages: 618-624
  • DOI: 10.1097/tp.0000000000000305
  • Peer Reviewed
• [Journal Article] Inhibitory effect of p53 in mitochondrial content and function during adipogenesis. (2014)
  • Author(s): Okita N, Ishikawa N, Oku M, Nagai W, Suzuki Y, Mizunoe Y, Matsushima S, Mikami K, Okado H, Sasaki T, Higami Y.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 446 Issue: 1 Pages: 91-97
  • DOI: 10.1016/j.bbrc.2014.02.059
  • Peer Reviewed
• [Presentation] Novel regulatory mechanism of PARP1 protein mediated by MDM2 inhibitors. (2016)
  • Author(s): Okita N., Matsushima S., Nagai W., Higami Y.
  • Organizer: The International Postgraduate Conference 2016
  • Place of Presentation: Noda, Chiba, Japan
  • Year and Date: 2016-02-27
  • Int'l Joint Research / Invited
• [Book] AUTOPHAGY: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging (chapter Autophagy in adipose tissue ) (2016)
  • Author(s): Mizunoe Y, Sudo Y, Okita N, Higami Y
  • Total Pages: 23
  • Publisher: Elsevier
• [Book] Section 15. Other determinants of sensitivity, PARP Inhibitors for Cancer Therapy (Edited by Curtin N, Sharma R) (2015)
  • Author(s): Okita N, Shibata A
  • Total Pages: 593
  • Publisher: Springer