Beta Sitosterol Mitigates Diabetic Nephropathy By Facilitating The Expression Of Insulin Signalling And Modulating The Pro-Inflammatory Molecules In Experimental Diabetic Rats

Abstract

Background: One of most abundant antioxidative component of vegetable oil and other plants, β-sitosterol (SIT), is a highly effective anti-diabetic drug. Our previous studies have shown that β-sitosterol significantly improved glycaemic control in skeletal muscle and adipose tissue by facilitating insulin metabolic signalling molecules but its effects on the kidney is not known.Aim:The current study sought to determine whether SIT could also exert anti-diabetic effects by regulating insulin signalling and preventing inflammation the kidney, which is a major contributor to insulin resistance and diabetic nephropathy.To achieve this, adult male albino rats weredivided in to four groups. Group-1: control; Group 2; high fat diet-induced type-2 diabetic rats; Group 3: Diabetic rats treated with β-sitosterol (20mg/kg b.wt, orally for 30 days) and group-4: Type-2 diabetic rats treated with metformin (50mg/kg.b.wt, orally for 30 days).Methods:Insulin receptor (IR), insulin receptor substrate-2 (IRS-2), Akt and interleukin -6 (IL-6), and kidney injury molecules mRNA (KIM-1) were analysed by Real Time-PCR analysis using gene specific primers. Results:mRNA expression of insulin signalling molecules (IR/IRS-1/Akt) were significantly improved in diabetic animals treated with 20mg dose of β-sitosterol (p<0.05). Conversely, it reduced the mRNA levels of pro inflammatory signalling (IL-6) and gene involved in tissue remodelling (KIM-1) effectively (p<0.05). Conclusion:Our present findings for the first time clearly indicate that β-sitosterol attenuates insulin resistance in the kidney by modulating the expression of proinflamamtion and KIM-1. Therefore, β-sitosterol could be considered as a potential therapeutic natural drug candidate for the treatment of diabetic nephropathy and associated complications.