title: Insulin resistance in experimental alcohol-induced liver disease.
abstract: OBJECTIVE
  Chronic ethanol consumption impairs liver regeneration due, in part, to inhibition of insulin signaling. This study characterizes the mechanisms and consequences of ethanol-impaired insulin signaling in relation to oxidative injury and altered gene expression.
  
  
  METHODS
  Long-Evans rats were fed for 8 weeks with isocaloric liquid diets containing 0% (control) or 37% ethanol (caloric content). Livers were used to examine histopathology, indices of oxidative stress, gene expression required for insulin and insulin-like growth factor (IGF) signaling, insulin-responsive gene expression, i.e. glyceraldehydes-3-phosphate dehydrogenase (GAPDH) and aspartyl-asparaginyl-beta-hydroxylase (AAH), and competitive equilibrium binding to the insulin, IGF-I, and IGF-II receptors.
  
  
  RESULTS
  Chronic ethanol exposure caused liver injury with increased hepatocellular steatosis, inflammation, apoptosis, and increased immunoreactivity for activated caspase-3, 8-hydroxy-2'-deoxyguanosine, and 4-hydroxy-2,3-nonenol. These effects were associated with increased expression of IGF-I receptor, IGF-II, and IGF-II receptor, and expression of IGF-I, AAH, and GAPDH, which mediate energy metabolism and cell motility/remodeling, and reduced binding to the insulin receptor.
  
  
  CONCLUSIONS
  Chronic ethanol-induced liver injury causes insulin resistance with inhibition of insulin-responsive genes needed for metabolism, remodeling, and regeneration. In contrast, the IGF-I and IGF-II signaling mechanisms remain relatively preserved, suggesting that insulin-regulated hepatic functions may be selectively vulnerable to the toxic effects of ethanol.
authors.affiliation: Departments of Medicine, Liver Research Center, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. suzanne_delamonte_md@brown.edu
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: de la Monte
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Yeon
authors.forename: Ming
authors.initials: M
authors.lastname: Tong
authors.forename: Lisa
authors.initials: L
authors.lastname: Longato
authors.forename: Rajeev
authors.initials: R
authors.lastname: Chaudhry
authors.forename: Mao-Yin
authors.initials: MY
authors.lastname: Pang
authors.forename: Kevin
authors.initials: K
authors.lastname: Duan
authors.forename: Jack R
authors.initials: JR
authors.lastname: Wands
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects; D000434:Alcoholic Beverages / Q000009:adverse effects; D000818:Animals; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects; D015870:Gene Expression; D007333:Insulin Resistance / Q000235:genetics*; D008108:Liver Diseases, Alcoholic / Q000235:genetics / Q000503:physiopathology*; D008115:Liver Regeneration / Q000235:genetics / Q000502:physiology; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction
chemical_list: D000431:Ethanol