Elucidation of pathophysiological roles of endothelial PDK1 on glucose metabolism and pancreatic beta cells
| Project/Area Number |
17K16157
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | Kawasaki Medical School |
|---|
Principal Investigator |
OBATA ATSUSHI 川崎医科大学, 医学部, 助教 (10771298)
|
|---|
| Project Period (FY) |
2017-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | PDK1 / 血管内皮 / 膵β細胞 / 虚血 / Vascularity / インスリン抵抗性 / 骨格筋 / 糖代謝 |
|---|
| Outline of Final Research Achievements |
It was reported that endothelial cell specific-Irs2 knockout mice presented impaired glucose-stimulated insulin secretion in vivo due to decreased islet blood flow. However, endothelial cell-specific insulin receptor knockout mice showed no influence on beta-cell function. Thus, from the point of the roles of insulin-PI3K signaling in endothelial cells on pancreatic beta-cells, there are many things remained to be unraveled. Therefore, we focused on endothelial Pdk1, which is the downstream molecule of PI3K. Vascular endothelial-specific Pdk1 knockout mice presented reduced beta-cell mass and impaired beta-cell function both in vivo and ex vivo. These mice also presented reduced blood flow of pancreas and/or islets and hypoxia of pancreatic beta-cells, which lead to ER stress related apoptosis and inflammation in pancreatic beta-cells. We identified endothelial Pdk1 plays important roles for maintenance of beta-cell mass and function.
|
| Academic Significance and Societal Importance of the Research Achievements |
血管内皮インスリンシグナルについては様々な報告があり、血管内皮特異的にインスリン受容体を欠損させても膵β細胞には影響はなく、インスリン受容体の下流にあるIRS2は膵血流量を調整することで膵β細胞からのインスリン分泌調整に重要な役割があることが知られている。我々は血管内皮において、インスリンシグナルの更に下流にあるPDK1が膵β細胞の機能及び量に極めて重要であることを解明し、今後新たな糖尿病治療法へとつながる可能性を明らかにした。
|
Report
(3 results)
Research Products
(5 results)
