title: Improving glucose metabolism with resveratrol in a swine model of metabolic syndrome through alteration of signaling pathways in the liver and skeletal muscle.
abstract: OBJECTIVE
  We hypothesized that supplemental resveratrol would affect glucose metabolism in the skeletal muscle and liver to improve blood glucose control.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Hospital laboratory.
  
  
  METHODS
  Yorkshire miniswine.
  
  
  METHODS
  The swine developed metabolic syndrome by consuming a high-calorie, high–fat/cholesterol diet for 11 weeks. Pigs were fed either a normal diet (control) (n = 7), a hypercholesterolemic diet (HCC) (n = 7), or a hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/d) (HCRV) (n = 7). Animals underwent dextrose challenge prior to euthanasia and tissue collection.
  
  
  METHODS
  Measurements of glucose and insulin levels, skeletal muscle and liver protein expression, and liver function test results.
  
  
  RESULTS
  The HCC group had significantly increased blood glucose levels at 30 minutes as compared with the control and HCRV groups. The HCC group demonstrated increased fasting serum insulin levels and levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Oil red O staining demonstrated increased lipid deposition in the livers of the HCC animals. Immunoblotting in the liver showed increased levels of mammalian target of rapamycin, insulin receptor substrate 1, and phosphorylated AKT in the HCRV group. Immunoblotting in skeletal muscle tissue demonstrated increased glucose transporter type 4 (Glut 4), peroxisome proliferating activation receptor coactivator 1α, peroxisome proliferator-activated receptor α, peroxisome proliferator-activated receptor , and phosphorylated AKT at threonine 308 expression as well as decreased retinol binding protein 4 in the HCRV group. Immunofluorescence staining for Glut 4 in the skeletal muscle demonstrated increased Glut 4 staining in the HCRV group compared with the HCC or control groups.
  
  
  CONCLUSIONS
  Supplemental resveratrol positively influences glucose metabolism pathways in the liver and skeletal muscle and leads to improved glucose control in a swine model of metabolic syndrome.
authors: Division of Cardiothoracic Surgery, Department of Surgery, and Cardiovascular Research Center, Rhode Island Hospital, Providence, USA.
authors: Thomas A
authors: TA
authors: Burgess
authors: Michael P
authors: MP
authors: Robich
authors: Louis M
authors: LM
authors: Chu
authors: Cesario
authors: C
authors: Bianchi
authors: Frank W
authors: FW
authors: Sellke
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D004040:Dietary Carbohydrates / Q000009:adverse effects; D002149:Energy Intake; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology*; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D008111:Liver Function Tests; D024821:Metabolic Syndrome / Q000473:pathology / Q000503:physiopathology*; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*; D013267:Stilbenes / Q000494:pharmacology*; D013552:Swine; D013556:Swine, Miniature; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D007328:Insulin; D010936:Plant Extracts; D013267:Stilbenes; D000077185:Resveratrol