title: Chronic ethanol consumption up-regulates protein-tyrosine phosphatase-1B (PTP1B) expression in rat skeletal muscle.
abstract: OBJECTIVE
  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 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Endocrinology, Provincial Hospital affiliated to Shandong University, Institute of Endocrinology, Shandong Academy of Clinical Medicine, Ji-nan 250021, China.
authors.forename: Li
authors.initials: L
authors.lastname: GAO
authors.forename: Xu
authors.initials: X
authors.lastname: ZHANG
authors.forename: Fu-rong
authors.initials: FR
authors.lastname: WANG
authors.forename: Ming-feng
authors.initials: MF
authors.lastname: CAO
authors.forename: Xiu-juan
authors.initials: XJ
authors.lastname: ZHANG
authors.forename: Nan-nan
authors.initials: NN
authors.lastname: SUN
authors.forename: Jie
authors.initials: J
authors.lastname: ZHANG
authors.forename: Ling
authors.initials: L
authors.lastname: GAO
authors.forename: Jia-jun
authors.initials: JJ
authors.lastname: ZHAO
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D000431:Ethanol / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000096:biosynthesis*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D000431:Ethanol; D058539:Phosphatidylinositol 3-Kinase; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1