Abstract:

Diabetes mellitus is a significant global health issue, affecting 425 million people worldwide, with projections estimating an increase to 629 million by 2045. The need for potent pharmacological agents is urgent, as current oral hypoglycemic drugs have adverse side effects. Hesperidin, a bioflavonoid with anti-hyperglycemic and anti-hyperlipidemic properties, offers promise as a natural therapeutic option. This study aimed to evaluate hesperidin's molecular and epigenetic effects on insulin signal transduction in the gastrocnemius muscle of STZ-induced type 2 diabetic rats. Methods involved dividing fully-grown male Wistar rats into five groups: Healthy control, STZ-induced diabetic, Diabetes+Hesperidin (100mg/kg), Diabetes+Metformin (50mg/kg), and Control+Hesperidin. At the experiment's conclusion, blood samples and gastrocnemius muscle tissues were collected to measure fasting blood glucose, serum insulin, antioxidant enzymes, oxidative stress markers, and histopathological and mRNA expression of insulin signalling molecules. Data were analyzed using one-way ANOVA, with significance set at p<0.05. Results indicated that STZ-induced diabetic rats exhibited significant increases in hyperglycemia, hyperinsulinemia, dyslipidemia, and oxidative stress markers, along with reduced superoxide dismutase (SOD) activity. Histopathological analysis revealed reduced muscle fibres and disrupted skeletal fibres. Additionally, mRNA expression of IRS-1, Akt, and GLUT 4 was significantly reduced. Remarkably, hesperidin treatment normalized these altered parameters. In conclusion, hesperidin effectively regulates insulin signalling in skeletal muscle, reducing diabetic risk. Thus, hesperidin shows potential as a therapeutic candidate for treating type 2 diabetes and its associated complications.

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