Insulin and resveratrol act synergistically, preventing cardiac dysfunction in diabetes, but the advantage of resveratrol in diabetics with acute heart attack is antagonized by insulin

Resveratrol (RSV) a natural phenolic compound has been found to display cardiovascular protective and insulin sensitizing properties In this study the effects of RSV and its combination with insulin on mortality hemodynamics insulin signaling and nitrosative stress were compared in streptozotocin (STZ) induced diabetic rats with or without acute myocardial ischemia/reperfusion (I/R) injury Under normoxic conditions cardiac systolic and diastolic functions and insulin-mediated Akt/GLUT4 (glucose transpoitel 4) activation were impaired in STZ diabetic lats The combination of RSV and insulin significantly prevented the above diabetes-associated abnormalities Notwithstanding that the diabetic state rendered the animals more susceptible to myocardial I/R injury and the mortality rate and inducible nitric oxide synthase (iNOS)/nitrotyrosine protein expression and superoxide anion production were also further increased in I/R injured diabetic hearts In contrast RSV treatment alone resulted in a lower mortality rate (from 625 to 18%) and better cardiac systolic function than its combination with insulin RSV also inhibited INOS/nitrotyrosine protein overexpression and superoxide anion overproduction in I/R injured diabetic myocardium Hyperglycemia impairment of insulin signaling overexpression of INOS/narotyrosine and superoxide anion overproduction were markedly rescued by the combination treatment which did not show an improvement in mortality rate (30%) or cardiac performance over RSV treatment alone These results indicate that insulin and RSV synergistically prevented cardiac dysfunction in diabetes and this may be in parallel with activation of the insulin mediated Akt/GLUT4 signaling pathway Although activation of the protective signal (Akt/GLUT4) and suppression of the adverse markers (NOS nitrotyrosine and superoxide anion) were simultaneously observed in insulin and RSV combination treatment insulin counteracted the advantage of RSV in diabetics with acute heart attack (C) 2010 Elsevier Inc All rights reserved