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Adipocyte and Cell Biology

MiR-26b modulates insulin sensitivity in adipocytes by interrupting the PTEN/PI3K/AKT pathway

International Journal of Obesity volume 39, pages 1523–1530 (2015)Cite this article

Subjects

Abstract

Background:

MicroRNAs (miRNAs) have emerged as epigenetic regulators of metabolism and energy homeostasis. There is a growing body of evidence pointing to miRNAs that have important regulatory roles in insulin sensitivity.

Objective:

The aim of this work was to explore the expression and mechanism of action of miR-26b in obesity-related insulin resistance (IR) in adipocytes.

Methods:

Quantitative real-time PCR was performed to determine miR-26b expression in obese rodent models, human obesity subjects and insulin-resistant adipocytes. We analysed the roles of miR-26b overexpression and inhibition on glucose uptake in adipocytes. Western blotting was used to detect the levels of protein molecules involved in the phosphoinositide-3-kinase (PI3K) pathway. Bioinformatics and the Dual Luciferase Assay were used to identify the target gene of miR-26b. We assessed the regulatory roles of miR-26b on the phosphatase and tensin homologue (PTEN)/PI3K/AKT pathway and the relationship between miR-26b and the metabolism of human obese subjects.

Results:

Levels of miR-26b are reduced in visceral adipose tissue (VAT) in obese rodent models, human obesity and insulin-resistant adipocytes. MiR-26b promotes insulin-stimulated glucose uptake and increases insulin-stimulated glucose transporter type 4 translocation to the plasma membrane in human mature adipocytes. MiR-26b modulates insulin-stimulated AKT activation via inhibition of its target gene, PTEN, and significantly increases insulin sensitivity via the PTEN/PI3K/AKT pathway. The expression level of miR-26b negatively correlates with increasing body mass index and homeostasis model assessment for IR in human obese subjects.

Conclusion:

Decreased miR-26b expression in VAT may be involved in obesity-related IR by interrupting the PTEN/PI3K/AKT pathway.

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Acknowledgements

This project was supported by grants from the National Key Basic Research Program of China (2013CB530604), the State Key Program of National Natural Science Foundation of China (81330067), National Natural Science Foundation of China (No. 81170797), Natural Science Foundation of Jiangsu Province of China (BK2011107), the Program for Innovative Research Teams of Jiangsu Province (LJ201108) and Nanjing Technological Development Program (201104013).

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Author notes

  1. G Xu and C Ji: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Laboratory, The 82nd Hospital of the People’s Liberation Army, Huaian, China

    G Xu, C Zhao, L Song, N Zhang & Y Zhao

  2. Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China

    C Ji, C Shi & X Guo

  3. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

    G Song

  4. Institute of Pediatrics, Nanjing Medical University, Nanjing, China

    L Chen, L Yang, F Huang & L Pang

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Xu, G., Ji, C., Song, G. et al. MiR-26b modulates insulin sensitivity in adipocytes by interrupting the PTEN/PI3K/AKT pathway. Int J Obes 39, 1523–1530 (2015). https://doi.org/10.1038/ijo.2015.95

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