Study On The Mechanism In Tertiary Butylhydroquinone Improves Liver Steatosis In Type 2 Diabetes Mellitus

BackgroundType 2 diabetes mellitus?T2DM?is a kind of metabolic disease characterized by insulin resistance.The long-term existence of hyperglycemia in diabetes leads to liver steatosis.Therefore,ameliorated insulin resistance may play a central role in treating liver steatosis in T2DM.Tertiary butylhydroquinone?TBHQ?is the most commonly used synthetic antioxidant and can enhance the effect of insulin in vivo.TBHQ could also remarkably increase phosphorylation of Protein kinase B?AKT?,which could reflect insulin sensitivity in hepatocytes and nerve cells.However,the underlying mechanism of TBHQ increasing phosphorylation of AKT thus enhancing insulin effect is unclear.ObjectiveThis study was to evaluate the effects of TBHQ on type 2 diabetes mellitus liver steatosis and explore the underlying mechanisms.MethodsWe conducted streptozocin?STZ?injection and a high-sugar-high-fat diet on Apolipoprotein e knock out mice(ApoE^-/-)to form an animal model of high-fat-high-sugar.The following indicators were tested during the experiment,?1?Body weight,blood-glucose levels,postprandial blood glucose levels were detected on all the mice.?2?oral glucose tolerance test?OGTT?and insulin tolerance test?ITT?were detected on all the mice.?3?Serum insulin level was determined by elisa in mice.?4?The liver tissues were observed by hematoxylin-eosin staining?HE?.?5?p-phosphatidylinositol 3-kinase?p-PI3K?,p-AKT,glucose transporters 4?GLUT4?,glycogen synthase kinase 3??GSK3??protein levels of liver were measured by western blot.HepG2 cells were induced by HClO and insulin to develop insulin resistance.?6?cell apoptosis was detected by Hoechst staining.?7?p-PI3K,p-AKT,GLUT4,GSK3?protein levels of HepG2 cell were measured by western blot.?8?The PI3K/AKT signaling pathway and Adenosine 5‘-monophosphate-activated protein kinase?2?AMPK?2?factor and?-arrestin-2 factor were evaluated by western blot and transfection technique.Results?1?TBHQ reduced the blood glucose lever and insulin content,increase body weight,improved glucose tolerance and insulin tolerance,there were significant differences?P<0.05?.?2?TBHQ effectively alleviated liver steatosis of the diabetic mice.?3?TBHQ significantly up-regulated the expression of p-PI3K,p-AKT,GLUT4,GSK3?,AMPK?2 and?-arrestin-2 in the liver of diabetic mice,there were significant differences?P<0.05?.?4?TBHQ can alleviate the apoptosis of insulin resistance model cells.?5?TBHQ improved the expression levels of p-PI3K,p-AKT,GLUT4,GSK3?by activating AMPK?2 or?-arrestin-2 in HepG2 cells,there were significant differences?P<0.05?.ConclusionTBHQ alleviated liver steatosis in type 2 diabetes mellitus and the mechanism is due in part to activation AMPK?2 and?-arrestin-2 to upregulate phosphorylation of PI3K and AKT.