Oncotarget

Research Papers:

Metformin ameliorates skeletal muscle insulin resistance by inhibiting miR-21 expression in a high-fat dietary rat model

Jinyang Wang, Yanbin Gao, Lijun Duan _, Suhong Wei, Jing Liu, Liming Tian, Jinxing Quan, Qi Zhang, Juxiang Liu and Jinkui Yang

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Oncotarget. 2017; 8:98029-98039. https://doi.org/10.18632/oncotarget.20442

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Abstract

Jinyang Wang1,2,*, Yanbin Gao3,4,*, Lijun Duan5,*, Suhong Wei1,2, Jing Liu1,2, Liming Tian1,2, Jinxing Quan1,2, Qi Zhang1,2, Juxiang Liu1,2 and Jinkui Yang6

1Department of Endocrinology, Gansu Provincial People’s hospital, Lanzhou, China

2Gansu Provincial Key Laboratory of Endocrine and metabolism, Lanzhou, China

3School of Traditional Chinese medical, Capital Medical University, Beijing, China

4Beijing Key Laboratory of TCM Collateral Disease Theory Research, Beijing, China

5Department of Gynecology and Obstetrics, Gansu Provincial People’s Hospital, Lanzhou, China

6Department of Endocrinology, Beijing Tongren hospital of Capital Medical University, Beijing, China

*These authors have contributed equally to this work

Correspondence to:

Lijun Duan, email: [email protected]

Jinyang Wang, email: [email protected]

Keywords: miRNA; metformin; insulin resistance (IR); TGF-β/Smads; luciferase reporter gene assay

Received: April 08, 2017    Accepted: July 25, 2017    Published: August 24, 2017

ABSTRACT

Insulin resistance (IR) plays a major role in the pathogenesis of abdominal obesity, hypertension, coronary heart disease, atherosclerosis and diabetes. miR-21 and TGF-β/smads is closely related to IR. However, it remained elusive whether metformin improved skeletal muscle insulin resistance (IRSM) by regulating miR-21 and its target signal TGF-β1/smads expression. In this study, high-fat diet rats with IR model and IR-skeletal muscle L6 cells (L6-SMCs) model were established, insulin sensitive index (ISI) and Homeostasis model assessment of IR (HOMA-IR) were applied, miR-21 and TGF-β1/smads mRNA expression were examined by RT-PCR, smad3 and smad7 protein were detected by western-blotting and laser scanning confocal microscopy (LSCM), the valid target of miR-21 was detected by luciferase reporter gene assay. Here, we found that metformin dose-dependently decreased miR-21 expression, accompanied by the decrease of HOMA-IR and the increase of HOMA-ISI. Luciferase report gene assay showed that smad7 was an effective target of miR-21. miR-21 overexpression directly downregulated smad7 and indirectly upregulated smad3 expression. Interestingly, miR-21 expression positively correlated with HOMA-IR and negatively correlated with HOMA-ISI. In conclusion, our results demonstrated that metformin improved IRSM by inhibiting miR-21 expression, and that miR-21 may be one of the therapeutic targets for IR.


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