[Electroacupuncture improves glucose and lipid metabolism disorders in diabetic obese rats via PI3K/Akt/GLUT4 pathway].

Objectives: To observe the effect of electroacupuncture (EA) on glycolipid metabolism disorders and chronic inflammatory responses in insulin-resistant (IR) rats, so as to explore the mechanism of EA in the intervention of IR.

Methods: The successfully modeled ZDF (Lepr^fa/fa) rats were randomly divided into the model, EA, and medication groups, with 8 rats in each group. Eight homologous control Zucker lean rats (Lepr^+/fa) were taken as the control group. Rats in the EA group received EA treatment at bilateral "Sanyinjiao"(SP6) and "Zusanli"(ST36), continuous wave applied with a frequency of 15 Hz and a current intensity of 1 mA, 20 minutes per session, once a day. Rats of the medication group were given pioglitazone solution by gavage at a dose of 10 mg/kg, while rats in the control and model groups were given the same dose of 0.9% sodium chloride solution by gavage. The above treatments were all carried out continuously for 5 days a week and rested for 2 days, for a total of 8 weeks. During the experiment, the fasting body weight (FBW) was measured weekly, and the fasting blood glucose (FBG) was detected 1 day before sample collection. After sample collection, the contents of fasting insulin (FINS), free fatty acids (FFA), low-density lipoprotein (LDL), total cholesterol (TC), triglyceride (TG), tumor necrosis factor - α (TNF-α), interleukin (IL)-6, IL-1β, and monocyte chemoattractant protein-1 (MCP-1) in the serum of rats were detected by ELISA, and the insulin resistance index (HOMA-IR) was calculated. The pathological changes of skeletal muscle were observed after oil red O staining. The ultrastructure of rat skeletal muscle was observed by transmission electron microscopy. The protein expression levels of phosphatidylinositol 3-kinase (PI3K), glucose transporter 4 (GLUT4), and the phosphorylation level of protein kinase B (Akt) in the skeletal muscle tissue of rats were detected by Western blot.

Results: Compared with the control group, the FBW, FBG, serum contents of FINS, FFA, LDL, TG, TC, IL-1β, IL-6, TNF-α, MCP-1, and HOMA-IR in the model group were increased (P<0.05, P<0.01), the protein expressions of PI3K and GLUT4 in skeletal muscle and the phosphorylation level of Akt protein were decreased (P<0.01). Oil red O staining showed severe lipid accumulation in skeletal muscle, and transmission electron microscopy showed a large amount of ectopic lipid accumulation in skeletal muscle tissue, swelling and deformation of mitochondria, and fragmentation of some muscle fibers. Compared with the model group, the FBW of the EA group decreased after 6 weeks of treatment, while the FBW of the medication group increased after 2 weeks of treatment (P<0.05, P<0.01);the other indicators in the EA group and the medication group were all reversed (P<0.05, P<0.01);oil red O staining showed that the lipid droplets in skeletal muscle cells were significantly reduced, and the degree of lipid accumulation was alleviated;transmission electron microscopy showed that the ectopic lipid accumulation in skeletal muscle tissue was reduced, and the muscle fiber fracture was alleviated.

Conclusions: EA can improve the glucose and lipid metabolism disorders in IR rats, reduce the ectopic lipid accumulation in skeletal muscle, and relieve the inflammatory response. This effect may be related to the activation of the PI3K/Akt/GLUT4 signaling pathway.