The Regulatory Effect And Mechanism Of SelT Gene Knockout On Glucose And Lipid Metabolism In Female Mice

Selenoprotein T is a thioredoxin-like enzyme located in the endoplasmic reticulum with redox activity.It is not only related to glucose homeostasis,but also to the integrity of endocrine pancreatic tissue.Previous studies have found that conditional SelT knockout in the brain of mice can lead to increased oxidative stress levels in tissues,aggravating Parkinson’s disease.In addition,pancreatic conditional SelT knockout can lead to islet injury and decreased glucose tolerance.Therefore,SelT is closely related to diabetes,but the regulatory effect of SelT on insulin sensitivity and liver lipid metabolism is still unclear.Based on this,we constructed whole body SelT knockout mice to explore the relationship between SelT and insulin signaling pathway and oxidative stress.It is of great significance to reveal the role of SelT in a series of metabolic diseases such as diabetes.selenium,selenoprotein,selenoprotein T,insulin resistance,liver glucose and lipid metabolism and oxidative stress were described.On this basis,we investigated the effects of systemic SelT gene knockout on glucose and lipid metabolism in female mice in normal state and type 2 diabetes.The main results are as follows:（1）Under normal physiological state,compared with the wild type,the SelT knockout mice had significantly reduced fasting body weight and fasting blood glucose level.SelT knockout mice showed enhanced glucose clearance,improved insulin sensitivity,significantly reduced pyruvate tolerance,and decreased gluconeogenesis.The expression level of PEPCK gene was significantly reduced,and the expression level of GCK gene was significantly increased.The phosphorylation levels of IR,Akt and Fox O1 in the liver of SelT knockout mice were significantly increased,the insulin signaling pathway was enhanced,and insulin sensitivity was increased.The fat accumulation in the liver of systemic SelT knockout mice was significantly reduced,and the fat cell size was not significantly changed.These results suggest that,under normal physiological conditions,systemic SelT knockout can enhance the insulin signaling pathway and improve lipid accumulation in the liver of female mice.（2）Under the condition of type 2 diabetes induced by high fat diet,compared with the wild type,the fasting body weight and fasting blood glucose of SelT knockout mice were significantly reduced,glucose tolerance was improved,insulin sensitivity was enhanced,and insulin resistance index was not significantly changed.After SelT gene knockout,the weight of liver and white fat in the mice was significantly reduced,the liver index was significantly reduced,and the white fat index was decreased.The phosphorylation of IR and Akt in the liver of the knockout group was significantly increased,and the phosphorylation of GSK-3βwas in a certain trend.The contents of serum TC in the knockout group were significantly reduced,the contents of LDL-C and HDL-C/TC were not significantly changed,and the contents of TG and TC in the liver were significantly reduced.As can be seen from the section staining diagram,the hollow vacuoles in the liver of the knockout group were significantly reduced,the red lipid droplets in the oil red O staining were significantly reduced,and the fat cells were slightly smaller.HE staining of the pancreas showed that the islet cells of the knockout group were significantly smaller.The immunofluorescence staining of the pancreas showed that the insulin secretion of the knockout group was significantly reduced.After the SelT gene knockout,the GSH/GSSG value in the liver of the mice significantly decreased,and the MDA content significantly increased,while the MDA content and H₂O₂content in the muscles showed no significant changes.These results suggest that systemic SelT knockout improve liver fat accumulation and enhance insulin sensitivity in T2D mice.