Aucubin improves glucolipid metabolic disorder in T2DM mice via the miR-505- 5p/IGF1/FIT1/IRS1/PI3K signaling pathway

Diabetes is characterized by impaired glucolipid metabolism and chronic inflammation. Aucubin, a natural compound, has shown potential for improving metabolic disorders, but its mechanisms remain unclear. To investigate the effects of aucubin on glucolipid metabolism and the underlying mechanisms in diabetic mice. Diabetic mice were induced by a high-fat diet and streptozotocin. Aucubin was administered, and its effects on metabolic parameters, tissue injury, and molecular profiles were assessed. Fasting blood glucose, insulin, lipid levels, and inflammatory markers were measured. Liver and pancreatic tissues were examined for histological changes. MiRNA and mRNA expression profiles were analyzed using sequencing, and miRNA-mRNA regulatory pairs were identified. Cell transfection and western blotting were performed to validate the regulatory mechanisms. Aucubin significantly reduced fasting blood glucose, triglycerides, total cholesterol, and inflammatory factors, while increasing fasting insulin, pancreatic β-cell function, and high-density lipoprotein cholesterol. It also alleviated liver and pancreatic tissue injury. Transcriptomic analysis identified 143 differentially expressed miRNAs and 2835 differentially expressed mRNAs, with 69 mRNAs enriched in the PI3K/AKT and insulin resistance pathways. Aucubin downregulated miR-505-5p, which negatively regulated IGF1 expression, thereby affecting the FIT1/IRS1/PI3K signaling pathway. Aucubin exerts anti-diabetic effects by mediating miR-505-5p targeting IGF1 to regulate the FIT1/IRS1/PI3K signaling pathway, offering a potential therapeutic strategy for diabetes.