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Metformin downregulates miR223 expression in insulin-resistant 3T3L1 cells and human diabetic adipose tissue

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Abstract

Aims and designs

Metformin, an anti-diabetic drug, is the first line medication for the treatment of type 2 diabetes mellitus and some studies show its relationship with micro-RNAs. This study set up to determine the effect of metformin on miR223 expression and content of AKT/GLUT4 proteins in insulin resistant signaling in 3T3L1 cells and adipocyte of human diabetic patients.

Materials and methods

Subcutaneous adipose tissues were taken from newly diagnosed diabetic patients (HOMA-IR > 1.8), before and after three months treatment with 500 mg of metformin twice a day. Cellular homogenate was prepared and miR223 expression and AKT/GLUT4 protein expression were determined by quantitative real-time PCR and western blotting. The results were compared to insulin resistant 3T3L1 adipocytes that were treated with 10 mM Metformin.

Results

MiR223 expression was significantly overexpressed both in insulin-resistant 3T3L1 adipocytes compared to non-insulin resistant adipocytes and in human diabetic adipose tissue, compared to non-diabetics (P value < 0.01). Metformin treatment downregulated miR223 expression in both adipocytes and human diabetic adipose tissue. In contrast the IRS/PI3-K/AKT pathway signaling components, Akt and GLUT4 increased in insulin-resistant 3T3L1 adipocytes and human diabetic adipose tissue after three months of metformin treatment.

Conclusions

Metformin reduced insulin resistance in adipocytes by reduction of miR223 expression and improving of IRS/Akt/GLUT4 signaling pathways. Plasma miR223 expression of human diabetic patients was reduced by metformin treatment. These results point to a novel mechanism of miR223 in insulin resistance.

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Acknowledgements

The authors thank all the staff at Yazd Diabetes Research Center and the surgical team at Shahid Sadoughi Hospital. In addition, we are thankful for the contribution of the patients and control subjects who participated in this study.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Yousof Naghiaee, Fatemeh Pourrajab & Javad Mohiti-Ardakani

  2. Department of Biochemistry, Faculty of Medicine, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Reza Didehdar

  3. Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Fatemeh Pourrajab

  4. Department of Endocrinology, School of Medicine Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Masoud Rahmanian

  5. Department of General Surgery, School of Medicine Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Naeime Heiranizadeh

  6. Department of Oral Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Azra Mohiti

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  1. Yousof Naghiaee
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Naghiaee, Y., Didehdar, R., Pourrajab, F. et al. Metformin downregulates miR223 expression in insulin-resistant 3T3L1 cells and human diabetic adipose tissue. Endocrine 70, 498–508 (2020). https://doi.org/10.1007/s12020-020-02459-2

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