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|Title:||MicroRNA-223 regulates Glut4 expression and cardiomyocyte glucose metabolism||Authors:||Lu H.
|Issue Date:||2010||Publisher:||Oxford Academic||Citation:||Lu H., Buchan R.J., Cook S.A. (2010). MicroRNA-223 regulates Glut4 expression and cardiomyocyte glucose metabolism. Cardiovascular Research 86 (3) : 410-420. ScholarBank@NUS Repository. https://doi.org/10.1093/cvq010||Abstract:||AimsMicroRNAs (miRNAs) are important for cardiac function and tissue metabolism. The aim of the present study is to investigate the role(s) of miRNAs in the insulin-resistant heart.Methods and resultsLeft ventricular biopsies were collected from patients with or without type 2 diabetes and from patients with left ventricular dysfunction. Quantitative miRNA expression analyses of 155 miRNAs revealed that miR-223 was consistently upregulated in the insulin-resistant heart. We assessed the effects of miR-223 on glucose metabolism in neonatal rat cardiomyocytes where adenoviral-mediated overexpression of miR-223 increased glucose uptake. Using in silico miRNA target prediction programs, we prioritized candidate miR-223 target genes, but observed no effect of miR-223 on myocyte enhancer factor 2c or insulin-like growth factor 1 receptor, and an unexpected miR-223-induced increase in nuclear factor IA. We next examined the effects of miR-223 on insulin signalling and glucose transport proteins. Neither phosphoinositide 3-kinase (PI3K) signalling nor AMP kinase activity was affected by miR-223 overexpression, whereas glucose transporter 4 (Glut4) protein expression was increased. miR-223 overexpression-induced Glut4 protein expression in cardiomyocytes was necessary and sufficient for increased glucose uptake as demonstrated by siRNA knockdown of Glut4. Loss-of-function studies in vivo, using a synthetic miR-223 inhibitor, confirmed the effect of miR-223 on Glut4. Conclusion These data demonstrate a role for miR-223 in Glut4 regulation and glucose metabolism in the heart, reveal the pleiotropic effects of miRNAs across tissues, and show that miRNAs can upregulate target genes in terminally differentiated cardiomyocytes. � 2010 The Author.||Source Title:||Cardiovascular Research||URI:||http://scholarbank.nus.edu.sg/handle/10635/149271||ISSN:||86363||DOI:||10.1093/cvq010|
|Appears in Collections:||Staff Publications|
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