Abstract
OBJECTIVE: This study aimed to investigate whether electroacupuncture (EA) can regulate skeletal muscle glucose metabolism through the AMPK/PGC-1α/TFAM signaling pathway in a rat model of type 2 diabetes mellitus (T2DM). METHODS: T2DM was induced by feeding rats a high-fat, high-sugar diet followed by intraperitoneal streptozotocin (35 mg/kg). Rats were randomly assigned to five groups: model, EA, EA plus AMPK inhibitor (Compound C, 20 mg/kg, three times weekly), sham acupuncture (tail non-acupoint stimulation), and control. EA was applied at Zusanli, Sanyinjiao, and Weiwanxiashu for 20 min daily, six days per week, for four weeks. Random blood glucose (RBG) and body weight were monitored weekly. After intervention, fasting blood glucose (FBG), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), fasting insulin (FINS), and C-peptide (C-P) were measured, and HOMA-IR and ISI were calculated based on FBG and FINS. Skeletal muscle morphology was assessed by H&E staining; ATP levels were measured; and AMPK/PGC-1α/TFAM pathway related protein and gene expression were analyzed by Western blotting and RT-PCR. RESULTS: EA reduced RBG, body weight, FBG, TG, LDL-C, FINS, C-P levels, and HOMA-IR, while improving ISI. Moreover, EA enhances the expression of AMPK, PGC-1α, TFAM, and GLUT 4 at both the protein and mRNA levels, alleviates skeletal muscle cell injury, and increases ATP content in skeletal muscle. These beneficial effects are abolished by co-administration of an AMPK inhibitor. CONCLUSION: EA improves glycolipid metabolism and alleviates insulin resistance in T2DM rats, potentially via activation of the AMPK/PGC-1α/TFAM pathway. These effects may be linked to improved skeletal muscle function and glucose utilization. EA shows promise as a therapeutic strategy for T2DM, warranting further investigation into its mechanisms and clinical relevance.