The Role of Quercetin and Exercise in Modulating Apoptosis and Cardiomyopathy via PI3K/AKT/FOXO3 Pathways in Diabetic Obese Rats.

Abstract

Objective: Quercetin and exercise both have antidiabetic effects through decreasing blood glucose while increasing insulin sensitivity. Therefore, the present study aimed to investigate the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) exercises along with quercetin administration on apoptosis and cardiomyopathy in diabetic obese rats.

Materials and methods: In this experimental study, 35 male Wistar rats [diabetic rats for experimental groups and normal rats for healthy control (HC)] were divided into seven groups (for each group n=5): HC, diabetic control (DC), diabetic quercetin control (DQC), diabetic HIIT (DHT), diabetic MICT (DMT), DHT with quercetin (DQHT) and DMT with quercetin (DQMT). The rats were fed a high-fat diet (HFD) for 8 weeks and a low dose of streptozotocin (STZ) was administered to create a model of type 2 diabetes mellitus (T2DM). Eight weeks of HIIT and MICT with or without quercetin treatment were performed. Quercetin was used at 15 mg/kg, as a suspension in carboxymethyl cellulose (CMC) at a concentration of 0.5%. One-way analysis of variance with LSD's post-hoc test with a significant level of P≤0.05 was used to analyze data.

Results: Just 8 weeks of HIIT and MICT protected the protein content of PI3K, AKT, and FOXO3 and caspase-8 (Casp- 8) gene expression in heart tissues (P<0.05). Quercetin and both training protocols decreased blood glucose, while improving inflammatory markers and the lipid profile (P<0.05).

Conclusion: Reduction in blood glucose along with improvements in the inflammatory markers and the lipid profile by quercetin injection may be a promising approach for the development of new antidiabetic medications. In addition, both training protocols showed potentially successful diabetic cardiomyopathy treatments through modulating the FOXO3 and PI3K/AKT pathways.