2019 Fiscal Year Final Research Report
Role of estrogen and iNOS during the development of ovariectomy-induced hyperglycemia.
| Project/Area Number |
17K13227
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied health science
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| Research Institution | Takasaki University of Health and Welfare |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | エストロゲン / 一酸化窒素合成酵素(iNOS) / 卵巣摘出 / 糖尿病 / 酸化ストレス |
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| Outline of Final Research Achievements |
Some studies show that inducible nitric oxide synthase (iNOS) plays an important role in the development of insulin resistance in diet-induced obesity. An ovariectomized (ovx) animal is an experimental model for the investigation of postmenopausal pathologic changes due to estrogen deficiency. The aim of this study was to evaluate the role of estrogen and iNOS in the progress of diabetes.
Significant increases in blood glucose levels after glucose injection were observed in ovx mice compared to those in sham mice. And, spontaneous activity in ovx mice impaired those in sham mice. On the other hand, no significant differences in blood glucose levels were observed between the sham and ovx groups of iNOS knockout (KO) mice. In iNOS KO ovx mice, the amount of GLUT4 translocation to the cytoplasmic membrane was greater than the amounts in WT sham and ovx mice and iNOS KO sham mice. Estrogen may control GLUT4 translocation via suppressing iNOS expression.
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| Free Research Field |
薬理学、毒性学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、血糖値上昇におけるエストロゲン低下とiNOSの関与について研究した。iNOSは膵臓においてだけではなく、末梢組織である骨格筋でも機能を有しているのではないか？という仮説を立てた。この仮説を立証するため、iNOSと骨格筋における糖代謝との関連性、中脳辺縁系ドーパミン神経系に制御される自発的な気力・運動量にiNOSが与える影響に着目し、iNOSの機能性と血糖値との関連性を明らかにした。さらに、iNOSシグナル抑制による血糖降下作用についても解析することにより、iNOSの抑制作用が創薬標的になりうるかを検討した。本研究は、酸化ストレス抑制という新たな血糖降下作用の発見に繋がるものである。
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