2014 Fiscal Year Final Research Report
Pathophysiological study and the developments of therapy using mouse model of glutamate dehydrogenase disorder
| Project/Area Number |
24591522
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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 |
Pediatrics
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TOKUHARA Daisuke 大阪市立大学, 医学(系)研究科, 講師 (60448751)
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| Co-Investigator(Renkei-kenkyūsha) |
MORITA Takashi 大阪市立大学, 大学院医学研究科, 教授 (70150349)
SAHEKI Takeyori 熊本大学, 生命資源研究・支援センター, 特任教授 (10056070)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | グルタミン酸脱水素酵素 / 高アンモニア血症 / 高インスリン血症 / 動物モデル |
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| Outline of Final Research Achievements |
Hyperinsulinism hyperammonemia is caused by dysregulation of GDH activity, which induces insensitivity for GTP inhibition and the unregulated insulin secretion. We have made a transgenic mouse (TGM) to clarify the mechanism of hyperammonemia and to develop the therapy. The hetero-TGM showed an increase of GDH activity, mild hypoglycemia, and mild hyperammonemia, however no clinical symptoms. In metabolome analysis of the liver, brain, heart, and kidney; fatty acid metabolites were enhanced in all the organs. The substances before α-oxoglutarate decreased and the substances afterα-oxoglutarate increased in the glycolytic system and TCA cycle of the liver. Because of the increased Gln/Glu, decreased Orn, Cit, and As, and no decreased N-acetylglutamate, hyperamonemia is not caused by the reduction of carbamoyl phosphate synthase. We have to consider a new mechanism for hyperammonemia.
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| Free Research Field |
先天代謝異常症
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