title: Vodka and wine consumption in a swine model of metabolic syndrome alters insulin signaling pathways in the liver and skeletal muscle.
abstract: BACKGROUND
  The purpose of this study was to examine the effects of alcohol in the context of metabolic syndrome on insulin signaling pathways in the liver and skeletal muscle.
  
  
  METHODS
  Twenty-six Yorkshire swine were fed a hypercaloric, high-fat diet for 4 weeks then split into 3 groups: hypercholesterolemic diet alone (HCC, n = 9), hypercholesterolemic diet with vodka (HCVOD, n = 9), and hypercholesterolemic diet with wine (HCW, n = 8) for 7 weeks. Animals underwent intravenous dextrose challenge before euthanasia and tissue collection.
  
  
  RESULTS
  HCC, HCVOD, and HCW groups had similar blood fasting glucose levels, liver function test, and body mass index. Thirty and 60 minutes after dextrose infusion, HCVOD and HCW groups had significantly increased blood glucose levels compared with the HCC group. The HCW group had significantly increased levels of insulin compared with the HCC group. Immunoblotting in skeletal muscle demonstrated that alcohol up-regulates p-IRS1, IRS2, AKT, AMPKα, PPARα, Fox01, and GLUT4. In the liver, HCW had up-regulation of AKT, AMPKα, and GLUT4 compared with HCC. Skeletal muscle immunohistochemistry demonstrated increased sarcolemmal expression of GLUT4 in both alcohol groups compared with HCC.
  
  
  CONCLUSIONS
  Moderate alcohol consumption in a swine model of metabolic syndrome worsens glucose metabolism by altering activation of the insulin signaling pathway in the liver and skeletal muscle.
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Warren Alpert Medical School of Brown University, Providence, RI 02905, USA.
authors.forename: Nassrene Y
authors.initials: NY
authors.lastname: Elmadhun
authors.forename: Antonio D
authors.initials: AD
authors.lastname: Lassaletta
authors.forename: Louis M
authors.initials: LM
authors.lastname: Chu
authors.forename: Cesario
authors.initials: C
authors.lastname: Bianchi
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism*; D000434:Alcoholic Beverages; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D047493:PPAR alpha / Q000187:drug effects / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000378:metabolism / Q000494:pharmacology; D013552:Swine; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047493:PPAR alpha; C495692:SLC2A4 protein, human; D013267:Stilbenes; D000431:Ethanol; D000077185:Resveratrol