| Project/Area Number |
16K09760
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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 |
Metabolomics
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
荒木 栄一 熊本大学, 大学院生命科学研究部(医), 教授 (10253733)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | microRNA / インスリンシグナル / 糖尿病 |
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| Outline of Final Research Achievements |
We focused on miR-222, the expression of which was increased in the livers of high fat/high sucrose diet-fed mice injected with gold thioglucose (G+HFHSD). Overexpression of miR-222 in primary mouse hepatocytes attenuated Akt phosphorylation induced by insulin, indicating that miR-222 negatively regulates insulin signaling. As per in silico analysis, miR-222 potentially binds to the 3′ untranslated region (3′ UTR) of the IRS-1 gene, a key insulin signaling molecule. In fact, IRS-1 protein expression was decreased in the livers of G+HFHSD-fed mice. We further confirmed a direct interaction between miR-222 and the 3′ UTR of IRS-1 via luciferase assays. Our findings suggest that up-regulation of miR-222 followed by reduction in IRS-1 expression may be a viable mechanism of insulin resistance in the liver.
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| Academic Significance and Societal Importance of the Research Achievements |
本邦を含め世界中で肥満、糖尿病患者数は増加の一途を辿り、現社会における大きな問題の一つとなっている。肥満、糖尿病を予防・治療していくためには、その病態理解が重要であることは言うまでもない。近年、蛋白に翻訳されないnon-coding RNAが注目されており、我々はインスリン抵抗性とmicro RNAに注目し研究を行い、肝におけるインスリン抵抗性発症の一つの機序を明らかにした。microRNAは今後、疾患のバイオマーカーや治療への応用も期待されており、今後の研究が期待される。
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