Metformin downregulates miR223 expression in insulin-resistant 3T3L1 cells and human diabetic adipose tissue
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ORIGINAL ARTICLE
Metformin downregulates miR223 expression in insulin-resistant 3T3L1 cells and human diabetic adipose tissue Yousof Naghiaee1 Reza Didehdar2 Fatemeh Pourrajab1,3 Masoud Rahmanian4 Naeime Heiranizadeh5 Azra Mohiti6 Javad Mohiti-Ardakani1 ●
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Received: 28 April 2020 / Accepted: 8 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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 noninsulin 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/PI3K/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. Keywords Insulin resistance Metformin miR223 type 2 diabetes mellitus adipocytes 3T3L1 ●
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Introduction * Javad Mohiti-Ardakani [email protected] 1
Department of Biochemistry and Molecular Biology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2
Department of Biochemistry, Faculty of Medicine, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
3
Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
4
Department of Endocrinology, School of Medicine Shahid Sadoughi University of Medical Sciences, Yazd, Iran
5
Department of General Surgery, School of Medicine Shahid Sadoughi University of Medical Sciences, Yazd, Iran
6
Department of Oral Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Insulin resistance (IR), the main disorder in type 2 diabetes mellitus (T2DM), is lack of response to the normal
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