| 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 |
|
|---|
| 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
|
| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
|
|---|
| Keywords | 内分泌 / 内分泌学 / 小胞体ストレス / 糖尿病 / 膵再生 |
|---|
| 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.
|
