Abstract:Objective To investigate the effect of electroacupuncture on insulin resistance (IR) and the protein kinase B (AKT)/forkhead box transcription factor O1 (FoxO1) signaling pathway in rats with diabetes mellitus (DM) and nonalcoholic fatty liver disease (NAFLD). Methods Seven male SpragueDawley rats were randomly selected as control group and were fed with normal diet; 14 male SpragueDawley rats were selected and were given highsugar and highfat feed and intraperitoneal injection of streptozotocin citrate buffer to establish a model of DM with NAFLD. After successful modeling, the rats were randomly divided into model group and electroacupuncture group, with 7 rats in each group. The rats in the electroacupuncture group were given electroacupuncture at bilateral Zusanli, Pishu, Sanyinjiao, and Weiwanxiashu points once a day, 6 times a week for 4 consecutive weeks; the rats in the control group and the model group were not given any treatment. The levels of fasting blood glucose (FBG), insulin (INS), homeostasis model assessment of insulin resistance (HOMAIR), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured for all groups; HE staining was used to observe liver histomorphology; Western blot was used to measure the protein expression levels of AKT, FoxO1, and phosphoenolpyruvate carboxykinase (PEPCK) in the liver. Results Compared with the control group, the model group had significant increases in FBG, INS, HOMAIR, ALT, and AST (P<0.05), as well as a significant reduction in the protein expression level of AKT and significant increases in the protein expression levels of FoxO1 and PEPCK in liver tissue (P<0.05); compared with the model group, the electroacupuncture group had significant reductions in FBG, INS, HOMAIR, ALT, and AST (P<0.05), as well as a significant increase in the protein expression level of AKT and significant reductions in the protein expression levels of FoxO1 and PEPCK in liver tissue (P<0.05). HE staining showed that the model group had an unclear lobular structure, swelling of most cells with unclear boundaries, and the presence of lipid droplets with varying sizes in the cytoplasm of hepatocytes, and the electroacupuncture group had a slightly disordered structure of hepatic lobules, swelling of some hepatocytes, and a small number of lipid droplets in the cytoplasm of hepatocytes. Conclusion Electroacupuncture can significantly downregulate FBG, INS, and HOMAIR, improve IR, and promote the repair of damaged liver tissue, possibly by regulating the AKT/FoxO1 signaling pathway.