Protection Of Diabetes-induced Cardiomyopathy By Resveratrol And Its Effects On Glycogen Synthase Kinase3Beta (GSK-3beta) And By The Protein Kinase (AKT2) Activities

This study was undertaken to investigate whether resveratrol protects theheart from diabetic injuries, and if so to ascertain whether its effect is mediatedby the glycogen synthase kinase3beta (GSK-3beta) and by the protein kinase(AKT2) activities. Thirty male albino mice were randomly divided into threegroups (n=10, for each), including control group, diabetic and diabetic-received resveratrol groups. Both, diabetic mice group and diabetic mice-received resveratrol group showed a similar high blood glucose level inducedby streptozotocin (STZ) injection. Western blot analysis showed that incomparison to non-diabetic control group, heart tissues of diabetic mice werefound to have significantly increased phosphorylated GSK-3beta (pGSK-3beta)and a significantly decreased phosphorylated AKT2(pAKT2) activities.However, a significant decrease in the level of pGSK-3beta and asignificant increase in pAKT2were indicated in the heart tissues of diabeticmice-that received resveratrol, as compared to diabetic group. Theinflammatory cytokines (TNF-α, PAI-1and ICAM-1) mRNA expression in theheart tissues were analyzed by real-time polymerase chain reaction (PCR) andshowed that their levels in diabetic group were increased about four times ofthose of control group. However, their expression levels in diabetic mice-receiving resveratrol, were decreased to about third of that in diabetic controlgroup. Furthermore, immunohistochemical analysis showed that diabetic micethat received resveratrol have an ordered arrangement of myocardial cells withlow GSK-3beta expression as compared to that of the diabetic group whichshowed disordered myocardial cells arrangements with high GSK-3betaexpression. This study indicates firmly that resveratrol and the subsequentinactivation of GSK-3beta and activation of AKT2can protect markedly thediabetes-induced cardiomyopathy.