| Project/Area Number |
20390093
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Yamaguchi University |
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Principal Investigator |
TANIZAWA Yukio Yamaguchi University, 大学院・医学系研究科, 教授 (00217142)
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| Co-Investigator(Kenkyū-buntansha) |
OTA Yasuhru 山口大学, 医学部・附属病院, 講師 (60448280)
EMOTO Masahiro 山口大学, 医学部, 准教授 (50294640)
YUJIRI Toshiharu 山口大学, 大学院・医学系研究科, 准教授 (80346551)
TAKEDA Koumei 山口大学, 医学部・附属病院, 助教 (60467793)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2009: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2008: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
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| Keywords | Wolfram症候群 / 膵β細胞 / インスリン分泌 / 糖尿病 / 視神経萎縮 / 小胞体ストレス / エクソサイトーシス / インスリン / 分泌顆粒 / pioglitazone |
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| Research Abstract |
WFS1 gene, responsible for the Wolfram syndrome, also determines the susceptibility to type 2 diabetes. WFS1 protein localizes to the endoplasmic reticulum. Absence of WFS1 protein induce ER stress in β-cells, and β-cells lacking WFS1 protein is susceptible to the ER stress-induced apoptosis. In Wfs1^<-/-> mice, β-cell apoptosis is accelerated because of increased ER stress. Pioglitazone protects β cell from apoptosis by reducing systemic insulin resistance and ER stress in the β-cells. In addition, pioglitazone directly induced adrenomedullin expression in the β-cells, playing a role in this β-cell protection.
In pancreatic β-cells, WFS1 protein also exists in the insulin secretory granules, and play crucial roles in the maintenance of acidic milieu inside the granules. Intra-granular acidification is reported to be necessary for the "priming" of the granule for the exocytosis. In Wfs1^<-/-> mice, glucose-induced insulin secretion is impaired in the early stage before the β cell number is decreased. Roles of WFS1 protein in the secretory granules need to be further investigated.
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