miR-494-3p reduces insulin sensitivity in diabetic cardiomyocytes by down-regulation of insulin receptor substrate 1.
- Author:
Jie WU
1
;
Xing-Hua QIN
1
;
Zuo-Xu HOU
1
;
Zi-Hao FU
1
;
Guo-Hua LI
1
;
Hong-Yan YANG
1
;
Xing ZHANG
2
;
Feng GAO
1
Author Information
1. School of Aerospace Medicine, the Fourth Military Medical University, Xi'an 710032, China.
2. School of Aerospace Medicine, the Fourth Military Medical University, Xi'an 710032, China. zhangxing@fmmu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Animals;
Diabetes Mellitus, Experimental;
physiopathology;
Down-Regulation;
Insulin;
Insulin Receptor Substrate Proteins;
physiology;
Insulin Resistance;
MicroRNAs;
genetics;
Myocytes, Cardiac;
physiology;
Rats
- From:
Acta Physiologica Sinica
2019;71(2):271-278
- CountryChina
- Language:Chinese
-
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.
