| Project/Area Number |
17H01966
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Eating habits
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| Research Institution | Kobe University |
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Principal Investigator |
Kido Yoshiaki 神戸大学, 保健学研究科, 教授 (10335440)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
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| Keywords | 膵β細胞 / 高脂肪食 / 2型糖尿病感受性遺伝子 / 糖尿病 / 2型糖尿病 / 遺伝環境相互作用 |
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| Outline of Final Research Achievements |
We found that when there is a risk allele in Kcnq1 gene, a T2DM susceptibility gene, the expression of non-coding RNA Kcnq1ot1 was decreased. In addition, Kcnq1ot1 expression reduction was found to result in epigenetic alterations induced an increase in the expression of Cdkn1c and a decrease in the pancreatic β-cell mass. We have already reported that the transcription factor C/EBPβ accumulates in the pancreatic β-cells of high fat-fed mice. In vivo studies have shown that compared to control mice, Kcnq1ot1-truncated C/EBPβ-overexpressing mice show significantly higher blood glucose levels, smaller pancreatic β-cell mass, and enhanced expression of Cdkn1c in the pancreatic islets. The findings suggest that the introduction of epigenetic modifications in pancreatic β-cells may lead to enhanced binding of C/EBPβ to the Cdkn1c promoter, then an increase in the expression levels of Cdkn1c, and a decrease in pancreatic β-cell mass.
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| Academic Significance and Societal Importance of the Research Achievements |
わが国においては、不規則な食生活や運動不足の日々を送りながら糖尿病を発症しない人もいれば、規則正しい生活を心がけていながら糖尿病を発症する人もいる。現在の糖尿病医療においては、その違いを明確にすることはできていない。代表者は、遺伝・環境因子の相互作用が重要と考えており、家族歴、さらにKCNQ1遺伝子の変異を確認することにより、栄養指導の重要性が患者に伝わりやすくなるものと考えている。すなわち、特に栄養指導に重点をおくべき患者とそうでない患者に分けることができれば、医療者・患者両者のモチベーションも上がり、薬物に依存しない治療法であることから、医療経済への負担も軽減することが期待される。
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