The Role Of Dexmedetomidine To Insulin Resistance In Hepatocytes

PURPOSEDexmedetomidine(DEX)stabilizes intraoperative blood glucose levels and reduces insulin resistance(IR),a common perioperative complication.However,the molecular mechanisms underlying these effects remain unclear.Since endoplasmic reticulum stress(ERS)is a mechanism of IR,this study sought to examine whether DEX can effectively alleviate IR by reducing ERS.METHODSHepG2 and LO2 cells were treated with different concentrations of insulin.The glucose content assay and Cell Counting Kit-8(CCK-8)were then employed to determine the optimal insulin concentration capable of inducing IR without affecting cell viability.Insulin-resistant hepatocytes were cultured with different concentrations of DEX for 24 h,and the glucose concentration in the supernatant was measured.ERS was assessed by q PCR and western blotting.The latter was also used to quantify the expression of phosphorylated protein kinase B(p Akt),phosphoenolpyruvate carboxykinase(PEPCK),and glucose 6 phosphatase(G6Pase),which are key proteins involved in the action of insulin.RESULTSAfter 48-h of culturing with 10 ?g/ml insulin,glucose consumption in hepatocytes was found to be reduced.IR hepatocytes cultured with 10,100,or 1000 ng/ml DEX for 24 h showed a concentration-dependent increase in glucose consumption.Elevated m RNA and protein levels of ERS markers binding immunoglobulin protein(BIP)and ER protein 29(ERp29),were reversed by DEX treatment.Moreover,reduced p Akt and increased PEPCK and G6 Pase protein levels in IR hepatocytes were also restored following DEX treatment.CONCLUSIONDEX may alleviate IR in hepatocytes by reducing ERS serving to restore the activity of Akt and reduce gluconeogenesis and glycogenolysis.