Elucidation of activating Cori cycle caused by inhibition of PHD2 in liver
| Project/Area Number |
24659154
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MINAMISHIMA Yoji Andrew 慶應義塾大学, 医学部, 講師 (20593966)
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| Co-Investigator(Renkei-kenkyūsha) |
AKIKO Kubo 慶應義塾大学, 医学部, 特任講師 (50455573)
TAKAKO Hishiki 慶應義塾大学, 医学部, 講師 (10338022)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 低酸素 / PHD2 / エネルギー代謝 / Cori回路 |
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| Outline of Final Research Achievements |
Prolyl hydroxylase 2 (PHD2) is an oxygen sensor that regulate the activity of the hypoxia inducible factors in an oxygen dependent manner. The purpose of this study was to examine whether inactivation of PHD2 in the liver played an important role for activating Cori cycle and decreasing lactate levels in circulation.
Blood lactate levels after treadmill test or lactate tolerance test were significantly lower in PHD2-liver-specific knockout (PHD2-LKO) mice. The stable isotope labeled lactate incorporation assay revealed that livers of PHD2-LKO mice produced significantly greater amounts of glucose derived from the labeled lactate than controls, suggesting that the blockade of PHD2 in the liver helps improve lactic acidosis by activating gluconeogenesis from lactate.
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Report
(4 results)
Research Products
(1 results)
