Effect of Eight Weeks of Continuous Exercise and Resveratrol Supplementation on Insulin Resistance and Pyruvate Dehydrogenase Kinase 4 (PDK4) Expression in the Soleus Muscle of Elderly Diabetic Rats

Abstract

Background and objectives: Pyruvate dehydrogenase kinase 4 (PDK4) is an enzyme involved in the regulation of glucose and fatty acid metabolism and homeostasis. The purpose of this study was to investigate effects of continuous exercise and resveratrol supplementation on insulin resistance and expression of PDK4 in the soleus muscle of elderly rats with type 2 diabetes.Methods: After inducing diabetes in 42 old male rats (mean weigh: 250-300 g, aged about two years), the rats were randomly divided into six groups: healthy control, diabetic control, continuous exercise, supplementation, continuous exercise + supplementation and sham. The continuous exercise group was subjected to eight weeks of running, five sessions a week. Daily 20 mg/Kg body weight resveratrol supplementation was administered to the supplementation and supplementation + exercise groups. To evaluate insulin resistance, the HOMA-IR insulin resistance index was calculated as the product of insulin (μIU/mL) and glucose (mmol/L) divided by 22.5. Expression of the PDK4 gene in the soleus muscle was analyzed by RT-PCR. Data were analyzed with IBM SPSS Statistics 23 using one-way ANOVA and Tukey's post hoc test at a significance level of 0.05.Results: Resveratrol alone or combined with continuous exercise significantly increased PDK4 expression and slightly decreased insulin resistance in the subjects.Conclusion: Our results show that diabetes is associated with reduced PDK4 expression and increased insulin resistance. These effects can be effectively reversed in the soleus muscle of elderly diabetic rats by resveratrol supplementation alone or combined with continuous exercise.