Department of Endocrinology, Provincial Hospital affiliated to Shandong University, Institute of Endocrinology, Shandong Academy of Clinical Medicine, Ji-nan 250021, China.
Acta Pharmacol Sin. 2010 Dec;31(12):1576-82. doi: 10.1038/aps.2010.161. Epub 2010 Nov 22.
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.
rats received ethanol treatment at a daily dose of 0 (control), 0.5 (group L), 2.5 (group M) or 5 gxkg(-1) (group H) via gastric gavage for 22 weeks. In vivo insulin sensitivity was measured using a hyperinsulinemic-euglycemic clamp. Expression of PTP1B in skeletal muscles was examined at both the mRNA (real-time PCR) and protein (Western blot) levels. PTP1B activity was assayed with a p-nitrophenol phosphate (PNPP) hydrolysis method. Changes of insulin signaling in skeletal muscle were analyzed with Western blotting.
the activity and expression of PTP1B 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 gxkg(-1)xd(-1). Total IRβ 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.
chronic ethanol intake at 2.5 and 5 xkg(-1)xd(-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 PTP1B activity.
研究慢性乙醇摄入对大鼠骨骼肌蛋白酪氨酸磷酸酶-1B（PTP1B）和胰岛素受体信号通路的潜在影响。
大鼠通过胃灌胃每天接受 0（对照）、0.5（L 组）、2.5（M 组）或 5 gxkg(-1)（H 组）的乙醇处理，共 22 周。使用高胰岛素-正常血糖钳夹技术测量体内胰岛素敏感性。实时 PCR 和 Western blot 检测骨骼肌中 PTP1B 的 mRNA 和蛋白表达。用对硝基苯酚磷酸（PNPP）水解法测定 PTP1B 活性。用 Western blot 分析骨骼肌中胰岛素信号的变化。
在 2.5 和 5 gxkg(-1)xd(-1)剂量下，乙醇分别使骨骼肌中 PTP1B 的活性和表达增加 1.6 和 2.0 倍。在两个较高剂量下，乙醇还降低了总胰岛素受体β（IRβ）和胰岛素受体底物-1（IRS-1）及其磷酸化形式。此外，慢性乙醇消耗导致 IRS-1 与磷脂酰肌醇 3-激酶 p85 亚基的结合显著抑制，Akt 磷酸化抑制，丝裂原激活蛋白激酶磷酸化水平降低。
2.5 和 5 xkg(-1)xd(-1)的足够剂量的慢性乙醇摄入可下调大鼠骨骼肌中 IRβ、P-IRβ 和 IRS-1 的表达，以及 IRS-1 和 Akt 的磷酸化形式，可能是通过增加 PTP1B 的活性。
