Effect of Quercetin and Metformin on Glucose Transporter-4 Expression, Oxidative Stress, Inflammation Markers and Insulin Resistance in Type 2 Diabetes Mellitus

Background: Defects in glucose transporter-4 (GLUT-4) expression and function in the skeletal muscles and adipose tissue can be considered as the main cause of insulin resistance (IR) in type 2 diabetes mellitus (T2DM). Also, Oxidative stress and inflammation play a very important role in the development of IR and T2DM. Aim: Studying the effect of quercetin and metformin on GLUT-4 expression, oxidative stress, inflammation markers and IR in T2DM. Method: This study was carried out on 50 male Wistar rats which were divided into five groups; control, untreated diabetic rats, diabetic rats treated with metformin, diabetic rats treated with quercetin and diabetic rats treated with metformin and quercetin. Results: The use of metformin and quercetin separately produced significant decrease in plasma glucose, insulin, IL-6, TNF-α levels, HOMA-IR and TBARS level in skeletal muscle. Also, they caused significant elevation in the antioxidant enzyme activities in skeletal muscles with increased expression of GLUT-4 in the skeletal muscles and adipose tissue compared to the diabetic rats. Evidently, the quercetin effects were more significant than that of metformin on all the parameters except on HOMA-IR (similar significant improvement). Moreover, the combined use of quercetin and metformin produced highly significant improvement approaching control level in all the parameters than that observed by using either of them. Conclusion: The combined use of QC and MF improved hyperglycemia and IR by increasing the expression of GLUT-4 in skeletal muscles and adipose tissue together with the reversal of the oxidative stress and inflammatory states.