, Volume 60, Issue 12, pp 2443–2452 | Cite as

KLF10 transcription factor regulates hepatic glucose metabolism in mice

  • Xiaoying Yang
  • Qi Chen
  • Lihong Sun
  • Huabing Zhang
  • Lu Yao
  • Xiaona Cui
  • Yong Gao
  • Fude Fang
  • Yongsheng Chang



Abnormal activation of hepatic gluconeogenesis leads to hyperglycaemia. However, the molecular mechanisms underlying dysregulated hepatic gluconeogenesis remain to be fully defined. Here, we explored the physiological role of Krüppel-like factor 10 (KLF10) in regulating hepatic glucose metabolism in mice.


Hepatic KLF10 expression in wild-type C57BL/6J mice, the db/db mouse model of diabetes, the ob/ob mouse model of obesity and high-fat-diet-induced obese (DIO) mice was measured. Adenoviruses expressing Klf10 or Klf10-specific short-hairpin RNA were injected into wild-type C57BL/6J mice, db/db or DIO mice. Expression of gluconeogenic genes in the liver and blood glucose levels were measured. GTTs and pyruvate tolerance tests were performed. The molecular mechanism by which KLF10 regulates hepatic glucose metabolism was explored.


Hepatic KLF10 expression was regulated by nutritional status in wild-type mice and upregulated in diabetic, obese and DIO mice. Overexpression of KLF10 in primary hepatocytes increased the expression of gluconeogenic genes and cellular glucose output. C57BL/6J mice with KLF10 overexpression in the liver displayed increased blood glucose levels and impaired glucose tolerance. Conversely, hepatic KLF10 knockdown in db/db and DIO mice decreased blood glucose levels and improved glucose tolerance. Furthermore, luciferase reporter gene assay and chromatin immunoprecipitation analysis indicated that KLF10 activates Pgc-1α (also known as Ppargc1a) gene transcription via directly binding to its promoter region.


KLF10 is an important regulator of hepatic glucose metabolism and modulation of KLF10 expression in the liver may be an attractive approach for the treatment of type 2 diabetes.


Gluconeogenesis KLF10 PGC-1α Type 2 diabetes 



Adenovirus expressing green fluorescent protein


Adenovirus expressing Krüppel-like factor 10


Control adenovirus expressing short-hairpin RNA against luciferase


Adenovirus expressing short-hairpin RNA against Krüppel-like factor 10


Adenovirus expressing short-hairpin RNA against peroxisome proliferator-activated receptor, gamma, coactivator 1, alpha


Chromatin immunoprecipitation


Cyclic AMP response element-binding protein


Diet-induced obese


Krüppel-like factor


Peroxisome proliferator-activated receptor, gamma, coactivator 1α


Pyruvate tolerance test


Quantitative PCR


Short-hairpin RNA


Small interfering RNA


Sterol regulatory element-binding transcription factor


Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.


This work was supported by the National Natural Science Foundation of China (grant nos. 81471049, 81670749, 81700768 and 81730024).

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

YC contributed to the conception and design of the study. XY and QC contributed to the study design and acquisition and analysis of data. LS, HZ, LY, XC, YG and FF contributed to the analysis and interpretation of data. XY, QC and YC contributed to drafting or revising the article. All authors critically revised the manuscript and approved the final version. YC is the guarantor of this work.

Supplementary material

125_2017_4412_MOESM1_ESM.pdf (698 kb)
ESM (PDF 697 kb)


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Xiaoying Yang
    • 1
  • Qi Chen
    • 2
  • Lihong Sun
    • 3
  • Huabing Zhang
    • 1
  • Lu Yao
    • 1
  • Xiaona Cui
    • 1
  • Yong Gao
    • 1
  • Fude Fang
    • 1
  • Yongsheng Chang
    • 1
  1. 1.The State Key Laboratory of Medical Molecular Biology, Department of Molecular Biochemistry, Institute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingPeople’s Republic of China
  2. 2.Hangzhou Center for Disease Control and PreventionZhejiangPeople’s Republic of China
  3. 3.Center for Experimental Animal Research, Institute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingPeople’s Republic of China

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