Impaired oxidative endoplasmic reticulum stress response caused by deficiency of thyroid hormone receptor

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591359
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: University of Yamanashi
• Principal Investigator: FURUYA Fumihiko 山梨大学, 総合研究部, 助教 (90456450)
• Co-Investigator(Kenkyū-buntansha): KANESHIGE Masahiro 山梨大学, 総合研究部, 助教 (20377518) ; KOBAYASHI Tetsuro 公益財団法人冲中記念成人病研究所, 研究室, 研究員 (30113442) ; SHIMURA Hiroki 福島県立医科大学, 医学部, 教授 (40303416)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 内分泌

Outline of Final Research Achievements

In control adenovirus-infected pancreatic β-cells, palmitate enhanced the expression of ATF4 and heme oxygenase 1, which facilitates adaptation to oxidative ER stress. However, in AdshTRα-infected pancreatic β-cells, palmitate did not induce ATF4-mediated integrated stress response, and oxidative stress-associated apoptotic cell death was significantly enhanced. TRα-deficient mice or WT were fed a HFD for 30 weeks, and the effect of oxidative ER stress on pancreatic β-cells was analyzed. HFD-treated TRα-deficient mice had high blood glucose levels and low plasma insulin levels. In HFD-treated TRα-deficient mice, ATF4 was not induced, and apoptosis was enhanced compared with HFD-treated WT mice. These results indicate that endogenous TRα plays an important role for the expression of ATF4 and facilitates reduced apoptosis in pancreatic β-cells under ER stress.

Free Research Field

内分泌