2018 Fiscal Year Final Research Report
ChREBP regulates blood glucose level via the expression of GLUT2
| Project/Area Number |
16K01820
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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 |
Applied health science
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| Research Institution | Health Sciences University of Hokkaido (2018)
Kobe University (2016-2017) |
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Principal Investigator |
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| Research Collaborator |
UYEDA kosaku
SAKIYAMA haruhiko
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | ChREBP / GLUT2 |
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| Outline of Final Research Achievements |
ChREBP KO mice showed a decrease in GLUT2 mRNA expression levels in all tissues, except the kidney, compared to the wild type mice. Next, to investigate whether ChREBP binds to the active promoter region of GLUT2, a series of reporter plasmids were constructed, each with a 500 bp insert, located 2.0 kb upstream and up to 500 bp downstream of the transcription start site of GLUT2 gene. The promoter activities of ChREBP were measured in HepG2 cells and not all reporter vectors used in this study demonstrated active promoter-binding interactions. Furthermore, experiments using ChREBP-overexpressed stable cell line, under low glucose condition, showed no correlation between mRNA level of GLUT2 and protein level of ChREBP. These results suggest that ChREBP did not regulate GLUT2 expression directly, but that glucose metabolite(s), which were increased in cells by ChREBP activation, might be involved in the regulation of GLUT2 expression.
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| Free Research Field |
生活習慣病
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| Academic Significance and Societal Importance of the Research Achievements |
GLUT2の発現量がChREBP KOマウスの様々な臓器において減少したことから、ChREBPがGLUT2の発現を制御していることが明らかとなった。この結果は、ChREBPを標的とした血糖降下薬の開発につながると考えられるため、糖尿病治療に新たな選択肢を加えることができるという点において社会的意義は大きいと考えられる。また、本研究によりChREBPは血糖調節機能を有することが明らかとなり、これまでに明らかになっている生理機能であるグルコース代謝と脂質合成の他に、血糖調節機能というChREBPの新たな生理機能を明らかにしたという点において学術的意義も高いと考えられる。
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