Alteration of cellular status in diabetes and autophagy

• Project/Area Number: 26293220
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• 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): 藤谷 与士夫 順天堂大学, 医学(系)研究科(研究院), 准教授 (30433783) ; 三田 智也 順天堂大学, 医学部, 助教 (90532557)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000); Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
• Keywords: オートファジー / 膵β細胞 / 動脈硬化 / ApoE / 糖尿病

Outline of Final Research Achievements

In this study, we investigate how autophagy failure modify the pathophysiology observed in diabetic state. We revealed that in pancreatic beta cells,　the activation of autophagy weakens the toxicity induced by human IAPP. In addition, while model mice of atherosclerosis forms atheroma in artery, however, the morphology of the atherosclerotic lesions are quite different from those in human, we found that crossing with smooth muscle cell specific autophagy failure mode, model mice of atherosclerosis showed the similar morphology in the lesion to human atherosclerosis. These results suggest that autophagy failure plays critical role in the formation of human diseases.

Research Products

• [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (2016)
  • Author(s): Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, Adachi H, Adams CM, Adams PD, Adeli K, Adhihetty PJ, Adler SG, Agam G, Agarwal R, Aghi MK, Agnello M, Agostinis P, Aguilar PV, Aguirre-Ghiso J, Watada H. et al.
  • Journal Title: Autophagy Volume: 12 Pages: 1-222
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Minireview: Autophagy in pancreatic beta cells and its implication in diabetes. (2015)
  • Author(s): Watada H, Fujitani Y
  • Journal Title: Molecular Endocrinology Volume: 29 Issue: 3 Pages: 338-348
  • DOI: 10.1210/me.2014-1367
  • Peer Reviewed
• [Journal Article] Human IAPP-induced pancreatic β 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: 124 Issue: 8 Pages: 3634-44
  • DOI: 10.1172/jci69866
  • Peer Reviewed / Open Access