| Project/Area Number |
15K09284
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Tokyo Gakugei University (2016-2017)
The University of Tokyo (2015) |
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Principal Investigator |
SUZUKI Masashi 東京学芸大学, 保健管理センター, 教授 (90595662)
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| Co-Investigator(Kenkyū-buntansha) |
堀田 晶子 東京大学, 医学部附属病院, 助教 (20534895)
中村 元信 東京大学, 医学部附属病院, 助教 (40459524)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 近位尿細管 / ナトリウム輸送 / 糖新生 / Akt / mTORC / インスリン / NBCe1 / AKT |
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| Outline of Final Research Achievements |
Insulin is known to promote sodium transport and regulate gluconeogenesis in renal proximal tubules (PTs). Akt and mammalian target of rapamycin complexes (mTORCs) are key regulators in the insulin signaling pathway. However, the roles of Akt and mTORCs in PTs are poorly understood. In this study, we examined the components of insulin signaling in isolated human and rat PTs. Our data indicate that Akt2 and mTORC2, but not mTORC1 mediates insulin-stimulated sodium bicarbonate co-transporter 1 (NBCe1) activity. In addition, insulin decreased the expression of gluconeogenic genes in human and rat PTs. Furthermore, our data using specific inhibitors and siRNA showed that insulin-suppressed PT gluconeogenesis is mediated via the IRS1, Akt2 and bopth mTORC1 and mTORC2. These distinct pathways may play important roles in hypertension and hyperglycemia in metabolic syndrome and diabetes mellitus.
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