In silico and in vivo analysis to identify the antidiabetic activity of beta sitosterol in adipose tissue of high fat diet and sucrose induced type-2 diabetic experimental rats

Abstract

Adipose tissue is the primary site of storage for excess energy as triglyceride and it helps in synthesizing a number of biologically active compounds that regulate metabolic homeostasis. Consumption of high dietary fat increases stored fat mass and is considered as a main risk factor for metabolic diseases. Beta-sitosterol (β-sitosterol) is a plant sterol. It has the similar chemical structure like cholesterol. Clinical and experimental studies have shown that β-sitosterol has anti-diabetic, hypolipidemic, anti-cancer, anti-arthritic, and hepatoprotective role. However, effect of β-sitosterol on insulin signaling molecules and glucose oxidation has not been explored. Hence in the present study we aimed to discover the protective role of β-sitosterol on the expression of insulin signaling molecules in the adipose tissue of high-fat diet and sucrose-induced type-2 diabetic experimental rats. Effect dose of β-sitosterol (20 mg/kg b.wt, orally for 30 days) was given to high fat diet and sucrose-induced type-2 diabetic rats to study its anti-diabetic activity. Results of the study showed that the treatment with β-sitosterol to diabetes-induced rats normalized the altered levels of blood glucose, serum insulin and testosterone, lipid profile, oxidative stress markers, antioxidant enzymes, insulin receptor (IR), and glucose transporter 4 (GLUT4) proteins. Our present findings indicate that β-sitosterol improves glycemic control through activation of IR and GLUT4 in the adipose tissue of high fat and sucrose-induced type-2 diabetic rats. Insilico analysis also coincides with invivo results. Hence it is very clear that β-sitosterol can act as potent antidiabetic agent.

Keywords:

• β-sitosterol
• insulin signaling
• glucose uptake and oxidation
• adipose tissue
• high-fat diet and sucrose
• type-2 diabetes
• homology modeling
• molecular docking
• molecular dynamics

Acknowledgment

The authors would like to thank, the Professor and Head, Department of Endocrinology, University of Madras, Dr. A.L.M Post Graduate Institute of Basic Medical Sciences, Chennai-600113, India for providing radioisotope laboratory facility for the assessment of ¹⁴C-2-deoxyglucose uptake and ¹⁴C-glucose oxidation assays and for providing Chemidoc instrument facility (Bio-Rad Laboratories) for protein expression analysis.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Science and Engineering Research Board (SERB) - Early Career Research Award (ECRA),Government of India [Grant No: ECR/2016/000415 dated 21/09/2016].