Electroacupuncture alleviates insulin resistance and impacts the hypothalamic IRS-1/PI3K/AKT pathway and miRNA-29a-3p in a rat model of type 2 diabetes

OBJECTIVE: This study aimed to explore the effects of electroacupuncture (EA) in a rat model of type 2 diabetes mellitus (T2DM) by examining the hypothalamic miRNA-29a-3p, insulin receptor substrate (IRS)-1 / phosphatidylinositol 3-kinase (PI3K) / protein kinase B (AKT) / signal transducer and activator of transcription (STAT)3 pathway, as well as metabolic molecules including proopiomelanocortin (POMC), neuropeptide Y (NPY) and agouti-related protein (AgRP), with the goal of revealing the molecular mechanisms by which EA mitigates T2DM. METHODS: = 12 each). An additional 12 rats formed a healthy control group. Food intake, body weight and serum levels of fasting blood glucose (FBG), insulin, total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) were measured. Hypothalamic micro (mi)RNA-29a-3p expression was detected by quantitative polymerase chain reaction (qPCR), while insulin receptor signaling pathway intermediates and metabolic molecules were analyzed using Western blotting, qPCR and immunohistochemistry. RESULTS: After the EA intervention, T2DM rats showed a significant decrease in both food intake and body weight. In addition, there were reductions in serum concentrations of FBG, insulin, TC, TG and LDL. The homeostatic model assessment of insulin resistance (HOMA-IR) index also significantly declined. EA significantly decreased hypothalamic miRNA-29a-3p expression and enhanced IRS-1/PI3K/AKT/STAT3 pathway activity, while regulating POMC, NPY and AgRP expression. These effects of EA were at least partially reversed by LY294002 administration, which supports our hypothesis that EA mitigates T2DM via the hypothalamic IRS-1/PI3K/AKT pathway. CONCLUSION: EA may improve hypothalamic IR by activating the IRS-1/PI3K/AKT/STAT3 pathway and regulating POMC, NPY and AgRP, thereby reducing food intake, correcting metabolic imbalance and mitigating T2DM. The effect of EA on the IRS-1/PI3K/AKT pathway may involve miRNA-29a-3p downregulation.