miR-494-3p reduces insulin sensitivity in diabetic cardiomyocytes by down-regulation of insulin receptor substrate 1 / 生理学报
Acta Physiologica Sinica
; (6): 271-278, 2019.
Article
em Zh
| WPRIM
| ID: wpr-777189
Biblioteca responsável:
WPRO
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.
Texto completo:
1
Base de dados:
WPRIM
Assunto principal:
Fisiologia
/
Resistência à Insulina
/
Regulação para Baixo
/
Miócitos Cardíacos
/
MicroRNAs
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Diabetes Mellitus Experimental
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Proteínas Substratos do Receptor de Insulina
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Genética
/
Insulina
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
Zh
Ano de publicação:
2019
Tipo de documento:
Article