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Thursday, February 5, 2009

Chronic ethanol consumption resulting in the downregulation of insulin receptor-β subunit, insulin receptor substrate-1, and glucose transporter 4 expression in rat cardiac muscles

The objective of this study was to investigate the effect of chronic ethanol intake on the expression of insulin receptor β subunit (IR-β), insulin receptor substrate-1 (IRS-1), and glucose transporter 4 (Glut4) in rat cardiac muscle.

Forty-eight male Wistar rats were randomly classified into four groups and to each group, ethanol was administered daily at the respective doses of 0 (control, C), 0.5 g kg−1 (low ethanol, L), 2.5 g kg−1 (middle ethanol, M), and 5 g kg−1 (high ethanol, H). Twenty-two weeks later, the rats were anesthetized, and the left ventricle muscles were excised. The IR-β, IRS-1, and Glut4 mRNA levels in the cardiac muscle tissues were detected by reverse-transcription polymerase chain reaction (RT-PCR); The IR-β, tyrosine phosphorylation of IR-β (PY-IR-β), IRS-1, tyrosine phosphorylation of IRS-1 (PY-IRS-1), and Glut4 protein levels were measured by Western blotting.

Compared to the control group, the IR-β, IRS-1, and Glut4 mRNA levels in groups H and M decreased remarkably. In addition, the protein levels of IR-β, IRS-1, and Glut4 showed a corresponding decline in ethanol-treated groups, especially in group H. Moreover, the PY-IR-β and PY-IRS-1 protein levels decreased in the hearts of ethanol-treated rats with corresponding changes in the IR-β and IRS-1 protein levels.

The present study showed that chronic ethanol intake could downregulate the expression levels of IR-β, IRS-1, and Glut4 in rat cardiac muscles.

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