Naringin Prevents Diabetic-Induced Dysmetabolism in Male Wistar Rats by Modulating GSK-3 Activities and Oxidative Stress-Dependent Pathways

Type 2 diabetes mellitus (T2DM), characterized by insulin resistance and glucose dysmetabolism, is a major metabolic disorder accompanied with health and financial burden. Recently, research findings showed that orange peel extract (OPE) has health benefits such as improved insulin sensitivity and glucose metabolism. The present study aimed at establishing the role of naringin from OPE on T2DM-induced glucose and lipid dysmetabolism. Thirty male (30) Wistar rats were randomized into five groups: control, diabetes, diabetes + naringin, diabetes + orange peel, and diabetes + metformin. Oral administration was once per day for 28 days. After 28 days of treatment, naringin ameliorated the diabetes-induced increase in blood sugar, homeostatic model assessment (HOMA) IR, triglyceride, total cholesterol, triglyceride/high density lipoprotein, total cholesterol/high density lipoprotein, triglyceride glucose index, glucose synthase kinase-3, lactate, lactate dehydrogenase, malondialdehyde, c-reactive protein, and tumor necrosis factor α compared with the diabetic untreated animals. Furthermore, naringin reversed diabetes-induced decrease in serum insulin, HOMA B, HOMA S, quantitative insulin-sensitivity check index, high-density lipoprotein, total antioxidant capacity, superoxide dismutase, catalase, glucose transporter-4, and hepatic glycogen. This study showed that naringin prevented diabetes-induced dysglycemia and dyslipidemia via glucose synthase kinase-3 and oxidative stress-dependent pathways.