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科研成果: “The hepatic FOXQ1 transcription factor regulates glucose metabolism in mice”
作者: 时间:2017-09-08 微信分享:
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导读: 常永生课题组于2016年10月在” DIABETOLOGIA” 杂志发表研究论文“The hepatic FOXQ1 transcription factor regulates glucose metabolism in mice”。此研究发现FOXQ1 通过与FOXO1 DNA 结合区相互作用形成复合物,抑制FOXO1 调控下游糖异生相关基因G6Pase,进而抑制肝脏糖异生并使血糖下降。 

文章链接: https://link.springer.com/article/10.1007%2Fs00125-016-4043-z 


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        临床上广泛使用的降糖药物二甲双胍主要作用机制就是抑制肝脏的糖异生。所以研究肝脏的糖代谢和能量代谢,有助于找到新的治疗糖尿病的靶点。中国医学科学院基础医学研究所,“医学分子生物学国家重点实验室”的常永生研究团队通过研究发现FOXQ1 通过与FOXO1 DNA 结合区相互作用形成复合物,抑制FOXO1 调控下游糖异生相关基因G6Pase,进而抑制肝脏糖异生并使血糖下降。 


    【摘要】: AIM/HYPOTHESIS:Hepatic forkhead box q1 (FOXQ1) expression levels are regulated by nutritional and pathophysiological status. In this study we investigated the role of FOXQ1 in the regulation of hepatic gluconeogenesis. METHODS:We used multiple mouse and cell models to study the role of FOXQ1 in regulating expression of gluconeogenic genes, and cellular and hepatic glucose production. RESULTS:Expression of hepatic FOXQ1 was regulated by fasting in normal mice and was dysregulated in diabetic mice. Overexpression of FOXQ1 in primary hepatocytes inhibited expression of gluconeogenic genes and decreased cellular glucoseoutput. Hepatic FOXQ1 rescue in db/db and high-fat diet-induced obese mice markedly decreased blood glucose level and improvedglucose intolerance. In contrast, wild-type C57 mice with hepatic FOXQ1 deficiency displayed increased blood glucose levels and impaired glucose tolerance. Interestingly, studies into molecular mechanisms indicated that FOXQ1 interacts with FOXO1, thereby blocking FOXO1 activity on hepatic gluconeogenesis, preventing it from directly binding to insulin response elements mapped in the promoter region of gluconeogenic genes. CONCLUSIONS/INTERPRETATION:FOXQ1 is a novel factor involved in regulating hepatic gluconeogenesis, and the decreasedFOXQ1 expression in liver may contribute to the development of type 2 diabetes. 


本文通讯作者为常永生研究员,第一作者崔颖博士。该研究工作得到了国家自然科学基金和973项目的支持。


 医学分子生物学国家重点实验室