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miR-494-3p reduces insulin sensitivity in diabetic cardiomyocytes by down-regulation of insulin receptor substrate 1

WU Jie, QIN Xing-Hua, HOU Zuo-Xu, FU Zi-Hao, LI Guo-Hua, YANG Hong-Yan, ZHANG Xing^*, GAO Feng

School of Aerospace Medicine, the Fourth Military Medical University, Xi’an 710032, China

Abstract

More and more evidence suggests that microRNA is widely involved in the regulation of cardiovascular function. Our preliminary experiment showed that miR-494-3p was increased in heart of diabetic rats, and miR-494-3p was reported to be related to metabolism such as obesity and exercise. Therefore, this study was aimed to explore the role of miR-494-3p in diabetic myocardial insulin sensitivity and the related mechanism. The diabetic rat model was induced by high fat diet (45 kcal% fat, 12 weeks) combined with streptozotocin (STZ, 30 mg/kg), and cardiac tissue RNA was extracted for qPCR. The results showed that the level of miR-494-3p was significantly up-regulated in the myocardium of diabetic rats compared with the control (P < 0.05). The level of miR-494-3p in H9c2 cells cultured in high glucose and high fat medium (HGHF) was significantly increased (P < 0.01) with the increase of sodium palmitate concentration, whereas down-regulation of miR-494-3p in HGHF treated cells led to an increase in insulin-stimulated glucose uptake (P < 0.01) and the ratio of p-Akt/Akt (P < 0.05). Over-expression of miR-494-3p in H9c2 cell line significantly inhibited insulin-stimulated glucose uptake and phosphorylation of Akt (P < 0.01). Bioinformatics combined with Western blotting experiments confirmed insulin receptor substrate 1 (IRS1) as a target molecule of miR-494-3p. These results suggest that miR-494-3p reduces insulin sensitivity in diabetic cardiomyocytes by down-regulating IRS1.

Key words: miR-494-3p; type 2 diabetes; cardiomyocyte; insulin receptor substrate 1; insulin resistance

Received: 2018-07-21　　Accepted: 2018-10-30

Corresponding author: 张星　　E-mail: zhangxing@fmmu.edu.cn

DOI: 10.13294/j.aps.2018.0095

Citing This Article：

WU Jie, QIN Xing-Hua, HOU Zuo-Xu, FU Zi-Hao, LI Guo-Hua, YANG Hong-Yan, ZHANG Xing, GAO Feng. miR-494-3p reduces insulin sensitivity in diabetic cardiomyocytes by down-regulation of insulin receptor substrate 1. Acta Physiol Sin 2019; 71 (2): 271-278 (in Chinese with English abstract).