title: Does resveratrol improve insulin signaling in chronically ischemic myocardium?
abstract: BACKGROUND
  Resveratrol is a naturally occurring polyphenol believed to be cardioprotective. We previously demonstrated that resveratrol improves insulin signaling and glucose metabolism in liver and skeletal muscle of swine with metabolic syndrome. Although resveratrol has metabolic benefits in peripheral tissues, its effect on insulin signaling in ischemic myocardium (IM) is unclear. Therefore, we developed a clinically relevant swine model of metabolic syndrome and chronic myocardial ischemia to investigate the effects of resveratrol on insulin signaling in cardiac tissue.
  
  
  METHODS
  Thirteen male Yorkshire swine were fed a high-cholesterol diet for 4 wk then underwent surgical placement of an ameroid constrictor to their circumflex artery to induce chronic myocardial ischemia. The high-cholesterol control group was given no drug (n = 7). The experimental group was provided the same diet and received supplemental resveratrol (100 mg/kg/d) (n = 6). Tissue was harvested 7 wk after ameroid placement for western blot and histological analyses.
  
  
  RESULTS
  In IM, there was no significant difference between the two groups in the insulin signaling markers studied. In nonischemic myocardium, there was a significant decrease in phosphorylated AMP-activated protein kinase α (P = 0.021) in the group treated with resveratrol; otherwise, there were no significant differences between the groups. Immunostaining for glucose transporter 4 and Periodic acid-Schiff staining for myocardial glycogen stores was similar between the groups.
  
  
  CONCLUSIONS
  Resveratrol has complex effects on glucose metabolism. Although prior studies demonstrated that resveratrol supplementation improves insulin sensitivity in peripheral tissues, in chronically IM, there are no significant alterations.
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island.
authors.forename: Ashraf A
authors.initials: AA
authors.lastname: Sabe
authors.forename: Nassrene Y
authors.initials: NY
authors.lastname: Elmadhun
authors.forename: Michael P
authors.initials: MP
authors.lastname: Robich
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Dalal
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000502:physiology*; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*; D013267:Stilbenes / Q000494:pharmacology*; D013552:Swine
chemical_list: D002316:Cardiotonic Agents; D007328:Insulin; D013267:Stilbenes; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D000077185:Resveratrol
keywords: Chronic myocardial ischemia; Diabetes; Glucose metabolism; Insulin signaling; Metabolic syndrome; Resveratrol