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15.07.2016 | Article

The hepatic FOXQ1 transcription factor regulates glucose metabolism in mice

verfasst von: Ying Cui, Aijun Qiao, Tao Jiao, Huabing Zhang, Yuan Xue, Yongkang Zou, Anfang Cui, Fude Fang, Yongsheng Chang

Erschienen in: Diabetologia | Ausgabe 10/2016

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Abstract

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 glucose output. Hepatic FOXQ1 rescue in db/db and high-fat diet-induced obese mice markedly decreased blood glucose level and improved glucose 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 decreased FOXQ1 expression in liver may contribute to the development of type 2 diabetes.

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Titel: The hepatic FOXQ1 transcription factor regulates glucose metabolism in mice
verfasst von: Ying Cui
Aijun Qiao
Tao Jiao
Huabing Zhang
Yuan Xue
Yongkang Zou
Anfang Cui
Fude Fang
Yongsheng Chang
Publikationsdatum: 15.07.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 10/2016
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-016-4043-z

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The hepatic FOXQ1 transcription factor regulates glucose metabolism in mice

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Methods

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Conclusions/interpretation

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