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.

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 (ß-sitosterol) is a plant sterol. It has the similar chemical structure like cholesterol. Clinical and experimental studies have shown that ß-sitosterol has anti-diabetic, hypolipidemic, anti-cancer, anti-arthritic, and hepatoprotective role. However, effect of ß-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 ß-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 ß-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 ß-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 ß-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 ß-sitosterol can act as potent antidiabetic agent.

Molecular approach to identify antidiabetic potential of Azadirachta indica.

BACKGROUND: Azadirachta indica (Neem) is a medicinal plant, used in Ayurveda for treating various diseases, one of which is diabetes mellitus. It is known to possess antiinflammatory, antipyretic, antimicrobial, antidiabetic and diverse pharmacological properties. However, the molecular mechanism underlying the effect of A. indica on insulin signal transduction and glucose homeostasis is obscure. OBJECTIVE: The aim was to study the effects of A. indica aqueous leaf extract on the expression of insulin signaling molecules and glucose oxidation in target tissue of high-fat and fructose-induced type-2 diabetic male rat. MATERIALS AND METHODS: The oral effective dose of A. indica leaf extract (400 mg/kg body weight [b.wt]) was given once daily for 30 days to high-fat diet-induced diabetic rats. At the end of the experimental period, fasting blood glucose, oral glucose tolerance, serum lipid profile, and the levels of insulin signaling molecules, glycogen, glucose oxidation in gastrocnemius muscle were assessed. RESULTS: Diabetic rats showed impaired glucose tolerance and impairment in insulin signaling molecules (insulin receptor, insulin receptor substrate-1, phospho-IRS-1(Tyr632), phospho-IRS-1(Ser636), phospho-Akt(Ser473), and glucose transporter 4 [GLUT4] proteins), glycogen concentration and glucose oxidation. The treatment with A. indica leaf extract normalized the altered levels of blood glucose, serum insulin, lipid profile and insulin signaling molecules as well as GLUT4 proteins at 400 mg/kg b.wt dose. CONCLUSION: It is concluded from the present study that A. indica may play a significant role in the management of type-2 diabetes mellitus, by improving the insulin signaling molecules and glucose utilization in the skeletal muscle.