The Protective Effect of Dihydroartemisinin on Type 2 Diabetic Mice via Regulating Hepatic Glucose Output

There was an investigation into the hypoglycemic effects and potential mechanisms of dihydroartemisinin (DHA) on hepatic glycometabolism of type 2 diabetes mellitus (T2DM). The db/db mice and ApoE−/− mice induced by streptozotocin (STZ) were selected as diabetes models. The levels of FBG, body weight, glucose tolerance, insulin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were observed to evaluate the drug’s efficacy. The glycogen content, glucose-6-phosphate (G6P), hexokinase (HK) and glucose-6-phosphatase (G6pase) were detected in the livers. Histopathological studies were conducted on the pancreas and liver. Targeting proteins and signaling pathways of DHA were identified by quantitative proteomic. Western blotting examined the protein expression of forkhead box protein O1 (FOXO1) and calcium/calmodulin-dependent-protein kinase 2 (CAMK2) in the liver. This study demonstrated that DHA reduced FBG, improved insulin sensitivity, ameliorated glucose tolerance in two diabetes models while decreasing the ALT and AST levels in db/db mice. DHA promoted hepatic glucose metabolism and inhibited gluconeogenesis via CAMK2/FOXO1-mediated HK upregulation and G6pase downregulation. In conclusion, DHA exerts protective effects against T2DM related to maintain the blance of hepatic glucose.