title: Biphasic effects of chronic ethanol exposure on insulin-stimulated glucose uptake in primary cultured rat skeletal muscle cells: role of the Akt pathway and GLUT4.
abstract: BACKGROUND
  mild or moderate chronic alcohol intake has been shown to be associated with increased insulin sensitivity, while chronic alcohol abuse demonstrates a contrary effect. The mechanism underlying this biphasic effect has not yet been clarified. We investigated whether chronic ethanol exposure mediates biphasic changes on insulin sensitivity and whether the phosphatidylinositol 3-kinase/Akt pathway is involved in vitro.
  
  
  METHODS
  primary cultured rat skeletal muscle cells were exposed to ethanol (0-400 mM) for 24 h. Insulin sensitivity was assessed by the (3) H-labelled 2-deoxyglucose uptake assay. Phosphatidylinositol 3-kinase, cytosol and cell membrane glucose transporter-4 (GLUT4), as well as the Akt phosphorylated form, were analyzed by Western blots.
  
  
  RESULTS
  biphasic effects of ethanol on insulin sensitivity were observed in primary cultured skeletal muscle cells in a dose-dependent manner. Compared with the untreated group, 50 and 100 mM concentrations of ethanol resulted in a significant increase in 2-deoxyglucose uptake by 29 and 28%, respectively, while higher concentrations of ethanol (200, 400 mM) showed a significant decrease in 2-deoxyglucose uptake by 28 and 47%, respectively. The changes in glucose transport activity were in line with the changes in Akt Ser473 phosphorylation and GLUT4 expression in an ethanol dose-dependent biphasic manner. The phosphorylation of Akt and GLUT4 protein contents were up-regulated after treatment with low concentrations of ethanol (50, 100 mM) and down-regulated with high concentrations of ethanol (200, 400 mM) for 24 h.
  
  
  CONCLUSIONS
  ethanol mediates biphasic changes on insulin sensitivity at least in part via the Akt pathway and GLUT4 expression.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qu
authors.forename: Lina
authors.initials: L
authors.lastname: Zhao
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Peng
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Yang
authors.forename: Chenjiang
authors.initials: C
authors.lastname: Ying
authors.forename: Liping
authors.initials: L
authors.lastname: Hao
authors.forename: Xiufa
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction
chemical_list: D002492:Central Nervous System Depressants; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D000431:Ethanol; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose