Effects Of Artemisinin On Glucose And Lipid Metabolism In Db/db Mice And Its Mechanism

Objective:This study was designed to explore the effects of artemisinin(artemether)on glucose and lipid metabolism in type 2 diabetes model-db/db mice and its potential mechanism.Methods:Eight-week-old male C57BL/KsJ-db/db mice were divided into 4 groups(n=6):blank control group(NC group)(db/+ mice,1% methylcellulose gavage),diabetes group(DM group)(db/db mice,1% methylcellulose gavage),artemether 100 group(db/db mice,1% methylcellulose + artemether 100mg/kg gavage),Artemether 200group(db/db mice,1% methylcellulose + artemether 200mg/kg gavage)each group of6 each,a total of 4 weeks of intervention.The body weight of the mice was measured every 2 days,and the food intake of each group of mice was weighed every 3 days and the average daily food intake and body weight change were evaluated.The amount of water in the mice was measured every 2 days using a graduated water bottle,and the urine volume of the mice was measured every 3 days.Fasting blood glucose in mice was measured every 7 days.After 8 hours of fasting,blood was collected from the tail vein,and the fasting blood glucose of the mice was measured by Roche blood glucose meter and supporting test paper.The glucose tolerance test(IPGTT)and insulin tolerance test(IPITT)were used to evaluate the tolerance of glucose to insulin and the sensitivity to insulin.The serum total cholesterol(TC)and triglyceride were determined by biochemical kit.(TG),free fatty acid(FFA)levels.The mice were weighed and weighed.Morphological changes of mouse pancreas and liver were observed by HE staining.The expression of AMP-activated protein kinase(AMPK),glucose transporter 4(GLUT-4)and insulin receptor(IR ?)protein in mouse liver was analyzed by Western-blog method.Bioprotein chips were used to detect the expression of inflammatory factors in the liver.Results:1.Compared with the blank control group,the weight gain rate,food intake and water consumption of the diabetic group were significantly increased,while the food intake,drinking water and body weight growth rate of the two groups of artemether groups were significantly lower(P<0.05);2.The fasting blood glucose of the two groups was significantly decreased in the dose of artemether.Compared with the blank control group,the area under the IPGTT curve(AUC)was significantly increased in the diabetic group(P<0.05).The area under the IPGTT curve(AUC)of the artemether 200 group was significantly lower(P<0.05);3.Compared with the blank control group,the area under the IPITT curve(AUC)of the diabetic group was significantly increased(P<0.05),and the area under the IPITT curve(AUC)of the artemether 100 group and the artemether 200 group was significantly lower(P<0.05);4.Compared with the blank control group,the levels of cholesterol(TC),triglyceride(TG)and free fatty acid(FFA)in the diabetic group were significantly increased.Under the intervention of artemether,the TC and TG in the serum of the mice were significantly decreased.And FFA levels were dose-dependent(P<0.05);5.Artemether significantly ameliorated islet vacuolar degeneration in db/db mice;6.Artemether improved the size of liver and lipid deposition in mice,and improved hepatic steatosis in db/db mice;7.Artemether significantly increased the expression of AMPK,GLUT-4 and IR ?protein in mouse liver;8.Artemether can significantly increase the expression of CD27 L and CD30 in T cells,reduce the inflammatory mediators IL-2,IL-6 and liver inflammation-associated macrophage-derived chemokine(MDC),macrophage inflammatory protein(Expression of MIP-2)and macrophage inflammatory protein-1g and(MIP-1g)factors.Conclusion:1.Artemether can significantly reduce the body weight and blood glucose levels of db/db mice;2.Artemether is expected to improve glycolipid metabolism in db/db mice by activating the AMPK pathway;3.Artemether can prevent liver inflammation and fatty liver formation in db/db mice by improving the immune microenvironment.