| Project/Area Number |
23390080
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | Yamaguchi University |
|---|
Principal Investigator |
TANIZAWA Yukio 山口大学, 医学(系)研究科(研究院), 教授 (00217142)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OHTA Yasuharu 山口大学, 医学部, 准教授 (60448280)
TANABE Katsuya 山口大学, 医学部附属病院, 助教 (00397994)
TAGUCHI Akihiko 山口大学, 医学部, 講師 (20634744)
幡中 雅行 山口大学, 大学院・医学系研究科, 助教 (60572534)
|
|---|
| Project Period (FY) |
2011-04-01 – 2014-03-31
|
| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2012: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2011: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
|
|---|
| Keywords | 糖尿病 / インスリン / アポトーシス / ストレス / 膵β細胞 / Wolfram症候群 / インスリン分泌 / 小胞体ストレス / β細胞 / ウォルフラム症候群 |
|---|
| Research Abstract |
Wolfram syndrome is an autosomal recessive disorder characterized by insulin deficient diabetes and optic atrophy. Diabetes is caused by pancreatic b-cell apoptosis. In most patients, WFS1 gene is mutated. WFS1 gene is also a type 2 diabetes gene. We conducted a nation-wide survey for the Wolfram syndrome in Japan. In the patients, pancreatic b-cell death is caused by ER stress. In addition, beta-cells are functionally abnormal. That functional failure is at least in part, due to acidification defects inside the secretory granules. WFS1 protein exists on the secretory granule membrane, in addition to the ER membrane. In the secretory granule, it maintains intra-granular acidic milieu, that is important for "priming" of the granule exocytosis. We also studied the mechanism whereby ER stress causes b-cell apoptosis. We found that excessive Gsk-3b activity enhances ATF4 degradation leading to the apoptosis. We also studied relationship between clock genes and b-cell function.
|
