Ameliorative effect of resveratrol against type 2 diabetes in rats through triggering of autophagy and inhibition of mTOR pathway.

Abstract

Background: Type 2 diabetes mellitus (T2DM), which affects millions of individuals, has become a serious health problem. The mammalian target of rapamycin (mTOR) hyperactivation is a negatively involved autophagy that may in fact aid in the loss of β-cell function. Resveratrol (RSV) is a naturally occurring phytoalexin, mostly found in cereals, fruits, and vegetables that have antioxidant effects.Aim: In the current work, Wistar rats exposed to high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM were evaluated for resveratrol's protective effects on pancreatic functions, and mTOR-mediated autophagy.Materials and Methods: Four equal groups of forty male Wistar rats were created at random. Group 1 (G1) was maintained in typical control circumstances and given a balanced diet; G2, G3, and G4 were fed HFD for 10 weeks continuously; at the end of the 6th week injected I/P STZ as a single dose to induce T2DM. Three days after diabetic induction, G3 was received RSV daily for continuously 4 weeks. G4 was received RSV in addition to Chloroquine (CQ) as autophagy inhibitor.Results: The findings shown that RSV reduces the pancreatic dysfunctions brought on by HFD-STZ by inhibiting the mTOR pathway through decreasing the level of mTOR, Cas-3, and p62 and increasing the level of LC3. RSV activate autophagy and inhibit apoptotic-mediated cell death confirmed by transmission electron micrograph findings.Conclusion: RSV is thought to protect pancreatic cells by inhibiting the mTOR pathway, which regulates the transition between autophagy and apoptotic machinery in diabetic circumstances.