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Stevioside Attenuates Insulin Resistance in Skeletal Muscle by Facilitating IR/IRS-1/Akt/GLUT 4 Signaling Pathways:
Abilasha Deenadayalan1,2, Vijayalakshmi Subramanian1, Vijayalakshmi Paramasivan3
1Department of Anatomy, Saveetha Institute of Medical & Technical Sciences, Chennai 602 105, India.
Abstract:
Type-2 diabetes mellitus (T2DM), the leading global health burden of this century majorly develops due to obesity and hyperglycemia-induced oxidative stress in skeletal muscles. Hence, developing novel drugs that ameliorate these pathological events is an immediate priority. The study was designed to analyze the possible role of Stevioside, a characteristic sugar from leaves of Stevia rebaudiana (Bertoni) on insulin signaling molecules in gastrocnemius muscle of obesity and hyperglycemia-induced T2DM rats. Adult male Wistar rats rendered diabetic by administration of high fat diet (HFD) and sucrose for 60 days were orally administered with SIT (20 mg/kg/day) for 45 days. Various parameters were estimated including fasting blood glucose (FBG), serum lipid profile, oxidative stress markers, antioxidant enzymes and expression of insulin signaling molecules in diabetic gastrocnemius muscle. Stevioside treatment improved glucose and insulin tolerances in diabetic rats and restored their elevated levels of FBG, serum insulin and lipid profile to normalcy. In diabetic gastrocnemius muscles, Setvioside normalized the altered levels of lipid peroxidase (LPO), hydrogen peroxide (H2O2) and hydroxyl radical (OH*), antioxidant enzymes (CAT, SOD, GPx and GSH) and molecules of insulin signaling including insulin receptor (IR), insulin receptor substrate-1 (IRS-1) and Akt mRNA levels. Furthermore, Stevioside enhanced glucose uptake (GU) and oxidation in diabetic muscles by augmenting glucose transporter 4 (GLUT 4) synthesis very effectively in a similar way to metformin. Results of molecular docking analysis evidenced the higher binding affinity with IRS-1 and GLUT 4. Stevioside effectively inhibits oxidative stress and promotes glucose uptake in diabetic gastrocnemius muscles by activating IR/IRS-1/Akt/GLUT 4 pathway. The results of the in silico investigation matched those of the in vivo study. Hence, Stevioside could be considered as a promising phytomedicine to treat T2DM.
Insights
Stevioside, a natural compound, effectively combats oxidative stress and enhances glucose uptake in type-2 diabetes by activating key insulin signaling pathways in muscles, similar to metformin.
Area of Science:
- Biochemistry
- Pharmacology
- Metabolic Disorders
Background:
- Type-2 diabetes mellitus (T2DM) is a significant global health issue, often linked to obesity and oxidative stress in skeletal muscles.
- Developing novel therapeutic agents to mitigate these pathological processes is a critical medical priority.
Purpose of the Study:
- To investigate the potential of Stevioside, a compound from *Stevia rebaudiana*, in managing T2DM.
- To analyze its effects on insulin signaling molecules within the gastrocnemius muscle of rats with diet-induced obesity and hyperglycemia.
Main Methods:
- Rats were induced with T2DM using a high-fat diet and sucrose, then treated with Stevioside (20 mg/kg/day) for 45 days.
- Evaluated parameters included blood glucose, lipid profile, oxidative stress markers, antioxidant enzymes, and insulin signaling proteins (IR, IRS-1, Akt, GLUT 4).
- In silico molecular docking was performed to assess binding affinities with IRS-1 and GLUT 4.
Main Results:
- Stevioside treatment improved glucose and insulin tolerance, normalizing fasting blood glucose and serum lipid profiles.
- It reduced oxidative stress markers (LPO, H2O2, OH*) and enhanced antioxidant enzyme activity (CAT, SOD, GPx, GSH) in diabetic muscles.
- Stevioside upregulated insulin signaling molecules (IR, IRS-1, Akt mRNA) and augmented glucose transporter 4 (GLUT 4) synthesis, promoting glucose uptake and oxidation.
Conclusions:
- Stevioside effectively inhibits oxidative stress and promotes glucose uptake in T2DM skeletal muscles via the IR/IRS-1/Akt/GLUT 4 pathway.
- Its efficacy in vivo and in silico suggests Stevioside is a promising phytomedicine for T2DM treatment.
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