2018 Fiscal Year Final Research Report
Stimulatory effect of V-ATPase of Insulin on proximal tubules
Project/Area Number |
17K16071
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Kidney internal medicine
|
Research Institution | The University of Tokyo |
Principal Investigator |
|
Project Period (FY) |
2017-04-01 – 2019-03-31
|
Keywords | 酸塩基平衡 / インスリン / 近位尿細管 / 腎生理 / mTOR / mTORC2 |
Outline of Final Research Achievements |
We found that V-ATPase activity on the luminal side of renal proximal tubules was activated by insulin by using a freshly isolated proximal tubule which was obtained from mouse kidney cortex. This stimulation by insulin was almost completely suppressed by Akt inhibitor (Akt inhibitor VIII) and mTORC1/2 inhibitor (PP242), but not by mTORC1 inhibitor (Rapamycin). These results indicated that the stimulation of V-ATPase activity on the luminal side of renal proximal tubules by insulin is mediated via Akt/mTORC2 pathway.
|
Free Research Field |
腎生理学
|
Academic Significance and Societal Importance of the Research Achievements |
インスリンは近位尿細管管腔側におけるナトリウム輸送のみならず、酸塩基平衡の制御に関与していることが示された。このことから、高インスリン血症が酸血症に関与している可能性が示唆された。さらに、この制御にはmTORC2が関与していることが示唆された。mTORC2選択的な阻害剤は、腎疾患の創薬ターゲットになる可能性があると考えられる。
|