Diabetes, Metabolic Syndrome and Obesity (May 2020)
Artemether Regulates Metaflammation to Improve Glycolipid Metabolism in db/db Mice
Abstract
Wei Fu,1– 3 Yujin Ma,1– 3 Liping Li,1– 3 Jie Liu,1– 3 Liujun Fu,1– 3 Yu Guo,1– 3 Zhiyin Zhang,1– 3 Jiaxi Li,1– 3 Hongwei Jiang1– 3 1Department of Endocrinology, The First Affiliated Hospital and Clinical Medicine College, Henan University of Science and Technology, Luoyang 471003, People’s Republic of China; 2National Center for Clinical Research of Metabolic Diseases, Luoyang Center for Endocrinology and Metabolism, Luoyang 471003, People’s Republic of China; 3Diabetic Nephropathy Academician Workstation of Henan Province, Luoyang 471003, People’s Republic of ChinaCorrespondence: Hongwei JiangEndocrinology Department, The First Affiliated Hospital and Clinical Medicine College, Henan University of Science and Technology, Luoyang 471003, People’s Republic of ChinaTel +86 13653880139Email [email protected]: Artemether, a commonly used artemisinin derivative, has been shown to possess potential antidiabetic activities. However, only limited information is available on the mechanisms of artemether in type 2 diabetes. Therefore, in this study, we examined some of the possible mechanisms of artemether (ATM) upon glycolipid metabolism in the db/db mouse model of diabetes.Materials and Methods: Male C57BL/KsJ-db/db and C57BL/KsJ-db/+ mice at 4 weeks of age were divided into four groups (N=6/group): (1) NC (normal control – db/+ mice, 1% methylcellulose, intragastric administration), (2) DM (diabetic model – db/db mice, 1% methylcellulose, intragastric administration), (3) ATM 100 (DM + 100 mg/kg of artemether) and (4) ATM 200 (DM + 200 mg/kg of artemether). A number of assays related to diabetes were then performed following a 4-week period of these treatments.Results: Artemether at both doses significantly reduced rates of weight gain and fasting blood glucose levels, improved islet function and insulin resistance and reduced serum lipid levels to varying degrees in db/db mice. Artemether exerted a positive effect on islet vacuolar degeneration and hepatic steatosis, and increased expressions of AMP-activated protein kinase, glucose transporter 4 and Insulin receptor β protein in the liver of these db/db mice. With the use of liver protein chip detection, we found that artemether significantly improved the immune microenvironment, down-regulated the expression of inflammatory factors and activated the cytokine-mediated signaling pathway through cytokine–cytokine receptor interactions.Conclusion: Artemether may regulate glycolipid metabolism in db/db mice by improving the immune microenvironment. The results of this study provide important new information that can serve as the foundation for future research into the use of artemether as a means to improve glycolipid metabolism.Keywords: artemether, glycolipid metabolism, immune microenvironment, AMPK, type 2 diabetes
