Diabetic cardiomyopathy is a leading cause of morbidity and mortality, and Insulin2 mutant (Ins2+/-) Akita is a genetic mice model of diabetes relevant to humans. Dicer,
miRNAs, and inflammatory
cytokines are associated with
heart failure. However, the differential expression of
miRNAs, dicer, and inflammatory molecules are not clear in
diabetic cardiomyopathy of Akita. We measured the levels of
miRNAs, dicer, pro-inflammatory
tumor necrosis factor alpha (TNFα), and anti-inflammatory
interleukin 10 (IL-10) in C57BL/6J (WT) and Akita hearts. The results revealed increased heart to
body weight ratio and robust expression of
brain natriuretic peptide (BNP: a
hypertrophy marker) suggesting
cardiac hypertrophy in Akita. The multiplex RT-PCR, qPCR, and immunoblotting showed up regulation of dicer, whereas
miRNA array elicited spread down regulation of
miRNAs in Akita including dramatic down regulation of let-7a, miR-130, miR-142-3p, miR-148, miR-338, miR-345-3p, miR-384-3p, miR-433, miR-450, miR-451, miR-455, miR-494, miR-499, miR-500, miR-542-3p, miR-744, and miR-872. Conversely, miR-295 is induced in Akita. Cardiac TNFα is upregulated at
mRNA (RT-PCR and qPCR),
protein (immunoblotting), and cellular (immunohistochemistry and confocal microscopy) levels, and is robust in hypertrophic cardiomyocytes suggesting direct association of TNFα with
hypertrophy. Contrary to TNFα, cardiac
IL-10 is downregulated in Akita. In conclusion, induction of dicer and TNFα, and attenuation of
IL-10 and majority of
miRNA are associated with
cardiomyopathy in Akita and could be used for putative therapeutic target for
heart failure in diabetics.