Stevioside Supplementation Reverses High-Fat Diet-Induced Insulin Resistance in Diabetic Rats: A Gastrocnemius Muscle Study

Abstract

Introduction: Insulin resistance (IR) is a hallmark of T2DM, primarily driven by an imbalance in glucose metabolism and insulin signaling, particularly in skeletal muscle. High-fat diet (HFD) consumption is known to exacerbate IR, leading to metabolic complications. Stevioside, a glycoside found in Stevia rebaudiana, has demonstrated anti-hyperglycemic properties, but its effects on skeletal muscle insulin resistance remain underexplored. Methodology: Male Wistar rats were subjected to a high-fat diet for 12 weeks to induce insulin resistance. The animals were then divided into control and stevioside treatment groups. The treatment group received oral stevioside supplementation (20 mg/kg) daily for six weeks. Fasting glucose, serum insulin, and HOMA-IR indices were measured. Western blot analysis of the gastrocnemius muscle was performed to quantify key proteins involved in insulin signaling: IRS-1, AKT, and GLUT4. Results: Stevioside treatment significantly improved fasting glucose levels, which decreased from 250 mg/dL to 130 mg/dL in the treated group. Serum insulin levels were also reduced, and HOMA-IR values indicated enhanced insulin sensitivity. Western blot analysis revealed a marked upregulation of IRS-1, AKT phosphorylation, and GLUT4 expression in the gastrocnemius muscle of the stevioside-treated group compared to controls. Discussion: The findings demonstrate that stevioside reverses HFD-induced insulin resistance by modulating insulin signaling pathways in skeletal muscle. The upregulation of IRS-1, AKT, and GLUT4 suggests that stevioside enhances glucose uptake and utilization in insulin-resistant tissues. These results align with previous studies on the hypoglycemic effects of stevioside in liver and adipose tissues. Conclusion: Stevioside supplementation significantly improves insulin sensitivity and restores insulin signaling in the gastrocnemius muscle, suggesting its potential as a therapeutic strategy for managing T2DM.