Potential mechanism of Jatropha gossypifolia phenolic derivatives in enhancing insulin-signalling cascades GLUT 4, IRβ and GSK-3β in streptozotocin nicotinamide induced type II diabetic in wistar rat model

Abstract

Objective: Diabetes mellitus is a metabolic syndrome that alters the composition of carbohydrates, proteins and fat content in the body due to decreased insulin secretion. This disrupts the insulin-signaling cascade, resulting in failure in the targeted tissues, such as insulin-stimulated glucose absorption muscle and fat. Natural products such as plants, which are rich in nutrient, offer a wide range of treatments for a number of diseases and infections including diabetes mellitus. Hence, this study investigates the anti-hyperglycemic efficacy of the methanolic leaves extract of Jatropha gossypifolia in experimental diabetic rats. Methods: Phytochemical constitution of J. gossypifolia showed tannin content to be significantly increased in methanolic extract and HPLC analysis also revealed phenolic derivative tannic acid to be main constitution. An intraperitoneal administration of 110 mg/kg body weight (b.w) nicotinamide and 45 mg/kg b.w. streptozotocin was provided to male Wistar albino rats, thus inducing diabetic. Diabetic induced rats treated with methanolic leaves extract of J. gossypifolia at the concentration between 100 and 50 mg/kg for 35 days. Periodic blood glucose level and body weight were measured. Methanolic extract influence was evaluated with q-PCR and western blot analysis on the cellular targets of insulin signaling cascades. Results: The results showed the decrease in blood glucose levels and increased serum insulin level in treated groups was significant (P < 0.05) in oral administration of methanol extract. Methanolic extract exhibited a profound increase in the gene expression of the cellular targets of insulin signaling cascade including IRTK, IRS1, PI3K, GS, GLUT 4 and a basal level expression of GSK-3β. In addition, methanolic extract increased protein expression of IRβ (2.7-fold), GSK-3β (2.5-fold) and GLUT 4 (2.4-fold) translocation as evidenced from western blot analysis with the plasma membrane fractions. Conclusion: Conclusively, methanolic leaves extract of J. gossypifolia exhibited a profound anti-hyperglycemic activity by modulating the expression of the key targets of insulin signaling pathway.

Keywords

• Jatropha gossypifolia
• Wistar albino rats
• Streptozotocin–nicotinamide induction
• Gene and protein expression
• Anti-hyperglycemic activity