Chronic ethanol consumption up-regulates proteintyrosine phosphatase-1B （PTP1B） expression in rat skeletal muscle

Aim： To investigate the potential effects of chronic ethanol intake on protein-tyrosine phosphatase-1B （PTP1B） and the insulin receptor signaling pathway in rat skeletal muscle. Methods： Rats received ethanol treatment at a daily dose of 0 （control）, 0.5 （group L）, 2.5 （group M） or 5 g·kg^-1 （group H） via gastric gavage for 22 weeks. In vivo insulin sensitivity was measured using a hyperinsulinemic-euglycemic clamp. Expression of PTPIB in skeletal muscles was examined at both the mRNA （real-time PcR） and protein （Western blot） levels. PTPIB activity was assayed with a p-nitrophenol phosphate （PNPP） hydrolysis method. Changes of insulin signaling in skeletal muscle were analyzed with Western blotting. Results： The activity and expression of PTPIB were dose-dependently elevated 1.6 and 2.0 fold in the skeletal muscle by ethanol, resepctively, at the doses of 2.5 and 5 g·k^-1·d^-1. Total IRI3 and IRS-1, as well as their phosphorylated forms, were decreased by ethanol at the two higher doses. Moreover, chronic ethanol consumption resulted in a significant inhibition of the association between IRS-1 and the p85 subunit of phosphatidylinositol 3-kinase, inhibition of Akt phosphorylation and reduced levels of mitogen-activated protein kinase phosphorylation. Conclusion： Chronic ethanol intake at 2.5 and 5 g·kg^-1·d^-1 sufficient doses can down-regulate the expression of IRβ, P-IRβ, and IRS-1, as well as the phosphorylated forms of IRS-1 and Akt, in rat skeletal muscle, possibly through increased PTPIB activity.