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Hepatic miR-181b-5p Contributes to Glycogen Synthesis Through Targeting EGR1

  • Shuyue Wang
  • Chen Liang
  • Huihan Ai
  • Meiting Yang
  • Jingwen Yi
  • Lei Liu
  • Zhenbo Song
  • Yongli Bao
  • Yuxin LiEmail author
  • Luguo SunEmail author
  • Huiying ZhaoEmail author
Original Article
  • 37 Downloads

Abstract

Background/Aim

The miR-181 family plays an important role in the regulation of various cellular functions. However, whether miR-181b-5p mediates hepatic insulin resistance remains unknown. In this study, we investigated the effect of miR-181b-5p on the regulation of hepatic glycogen synthesis.

Methods

The miR-181b-5p levels in the livers of diabetic mice were detected by real-time PCR. The glycogen levels and AKT/GSK pathway activation were examined in human hepatic L02 cells and HepG2 cells transfected with miR-181b-5p mimic or inhibitor. The potential target genes of miR-181b-5p were evaluated using a luciferase reporter assay and Western blot analysis. EGR1-specific siRNA and pCMV-EGR1 were used to further determine the role of miR-181b-5p in hepatic glycogen synthesis in vitro. Hepatic inhibition of miR-181b-5p in mice was performed using adeno-associated virus 8 (AAV8) vectors by tail intravenous injection.

Results

The miR-181b-5p levels were significantly decreased in the serum and livers of diabetic mice as well as the serum of type 2 diabetes patients. Importantly, inhibition of miR-181b-5p expression impaired the AKT/GSK pathway and reduced glycogenesis in hepatocytes. Moreover, upregulation of miR-181b-5p reversed high-glucose-induced suppression of glycogenesis. Further analysis revealed that early growth response 1 (EGR1) was a downstream target of miR-181b-5p. Silencing of EGR1 expression rescued miR-181b-5p inhibition-reduced AKT/GSK pathway activation and glycogenesis in hepatocytes. Hepatic inhibition of miR-181b-5p led to insulin resistance in C57BL/6 J mice.

Conclusion

We demonstrated that miR-181b-5p contributes to glycogen synthesis by targeting EGR1, thereby regulating PTEN expression to mediate hepatic insulin resistance.

Keywords

Hepatic glycogenesis miR-181b-5p EGR1 PTEN 

Notes

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81700709 and 81502284), the Research Foundation of Jilin Provincial Science & Technology Development (20180520105JH and 20170414028GH), the Fundamental Research Funds for the Central Universities (2412017DQ015), and the Changchun Science and Technology Bureau (17YJ003-1).

Compliance with ethical standards

Conflict of interest

The authors of this study declare that no conflicts of interest exist.

Supplementary material

10620_2018_5442_MOESM1_ESM.pdf (16.1 mb)
Supplementary material 1 (PDF 16459 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.National Engineering Laboratory for Druggable Gene and Protein Screening, School of Life SciencesNortheast Normal UniversityChangchunChina
  2. 2.Research Center of Agriculture and Medicine Gene Engineering of Ministry of EducationNortheast Normal UniversityChangchunChina
  3. 3.Department of GeriatricsThe First Hospital of Jilin UniversityChangchunChina

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