| Project/Area Number |
26460489
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | Yamaguchi University |
|---|
Principal Investigator |
OHTA Yasuharu 山口大学, 医学部, 准教授(寄附講座等) (60448280)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
田口 昭彦 山口大学, 医学(系)研究科(研究院), 助教 (20634744)
秋山 優 山口大学, 医学部附属病院, 助教 (90717547)
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| Project Status |
Completed (Fiscal Year 2016)
|
| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | 体内時計 / 時計遺伝子 / インスリン分泌 / 2型糖尿病 / 小胞体ストレス / 膵β細胞 / 概日リズム / 生体リズム / DBPシグナル |
|---|
| Outline of Final Research Achievements |
In Wfs1-/- Ay/a islets, Dbp expression decreased and E4bp4 expression increased, leading to reduced DBP transcriptional activity. Transgenic mice expressing E4BP4 under the control of the mouse insulin Ⅰ gene promoter (MIP), in which E4BP4 in β-cells is expected to compete with DBP for D-box, displayed remarkable glucose intolerance with severely impaired insulin secretion. Basal ATP/ADP ratios in MIP-E4BP4 islets were elevated without the circadian oscillations observed in wild-type islets. Neither elevation of the ATP/ADP ratio nor an intracellular Ca2+ response was observed after glucose stimulation. RNA expressions of genes involved in insulin secretion gradually increase in wild-type islets early in the feeding period. In MIP-E4BP4 islets, however, these increases were not observed. Molecular clock output DBP transcriptional activity, susceptible to ER stress, plays pivotal roles in β-cell priming for insulin release by regulating β-cell metabolism and gene expressions.
|
