Descending Expression of miR320 in Insulin-Resistant Adipocytes Treated with Ascending Concentrations of Metformin

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Descending Expression of miR320 in Insulin‑Resistant Adipocytes Treated with Ascending Concentrations of Metformin Yousof Naghiaee1 · Reza Didehdar2 · Zahra Malekpour‑Dehkordi1 · Fatemeh Pourrajab1,3 · Javad Mohiti‑Ardakani1,4 Received: 8 July 2019 / Accepted: 17 April 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Some miRNAs are supposed to play a role in insulin resistance and metabolic disorders. Such miRNAs can be differentially expressed in response to a pharmacologic intervention for insulin resistance as a biomarker/risk factor for insulin resistance. This study aimed at determining the effect of Metformin on miR320 expression in insulin-resistant (IR) adipocytes. The 3T3L1 cells were expanded in DMEM, differentiated into adipocytes by differentiating medium, became resistant to insulin, and then were treated with ascending concentrations of Metformin. Quantitative realtime PCR was performed to profile the miR320 expression in 3T3L1 adipocytes, IR adipocytes, and Metformin-treated IR adipocytes. Compared to the normal adipocytes, IR adipocytes exhibited a significantly higher level of miR320 expression, however, in response to Metformin graded concentrations, IR adipocytes down-regulated miR320 and were almost at normal level. The maximum effect of Metformin was at 10 mM. In IR adipocytes, miR320 expression is over-expressed which can be down-regulated by Metformin treatment. The findings provide some information on a potentially new marker to determine insulin resistance and to predict response to insulin resistance therapy. Keywords  Insulin resistance · Metformin · miR320 · Adipocytes · 3T3L1cell

* Javad Mohiti‑Ardakani [email protected] 1

Department of Biochemistry and Molecular Biology, School of Medicine, ShahidSadoughi University of Medical Sciences, Yazd, Iran

2

Department of Biochemistry, School of Medicine, Zabol University of Medical Sciences, Zabol, Iran

3

Nutrition and Food Security Research Center, ShahidSadoughi University of Medical Sciences, Yazd, Iran

4

Diabetes Research Center, ShahidSadoughi University of Medical Sciences, Yazd, Iran



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Biochemical Genetics

Introduction MicroRNAs (miRNAs) are small non-coding RNAs which play an important role in all aspects of biology and metabolic processes (Beltrami and Emanueli 2014). Studies report different expression of circulating miRNAs in individuals with insulin resistance and type 2 diabetes mellitus (T2DM) compared to healthy controls. Recently, miRNAs have been considered as novel biomarkers in such metabolic disorders (Deiuliis 2015; Fernandez-Valverde et al. 2011; Honardoost 2014; Mao et al. 2013; Chen et al. 2014; Demirsoy et al. 2018). However, it is expected that particular miRNAs should be involved in initiation, progression of specific aspects of T2DM pathologies such as insulin sensitivity, glucose homeostasis, and lipid metabolism (Beltrami and Emanueli 2014; Chien et  al. 2015; Hongmei and Leung 2015). One of the main metabolic aspects of T2DM is the low respon