Mechanism of Astragali Radix–Puerariae Lobatae Radix Compatibility Regulating Mitochondrial Autophagy through the PINK1/Parkin Pathway to Improve Insulin Resistance in T2DM Rats
Shuang Wei, Feng Hao, Wenchun Zhang, Huan XingBackground
Type 2 diabetes mellitus with insulin resistance (T2DM IR) is closely linked to mitochondrial dysfunction and ectopic lipid accumulation in liver tissue. Purpose: To explore the therapeutic effect and underlying mechanism of Astragali Radix-Puerariae Lobatae Radix compatibility (GQ) on mitochondrial autophagy in hepatocytes of T2DM IR rats via the PINK1/Parkin signaling pathway.
Materials and Methods
Male Sprague-Dawley rats were fed a high-fat diet and injected with streptozotocin to induce the T2DM IR model, followed by treatment with GQ, CCCP (inducer), or 3-MA (inhibitor) for 4 weeks. Glycolipid parameters, oxidative stress markers, hepatic histology, and mitochondrial ultrastructure were evaluated. Western blot was performed to measure the expression of LC3-II/I, PINK1, Parkin, TOM20, TIM23, and P62.
Results
T2DM IR model rats exhibited marked insulin resistance, lipid metabolic disorder, elevated ROS/MDA levels, damaged mitochondrial ultrastructure, and impaired autophagic flux. GQ treatment significantly reduced fasting blood glucose, HOMA-IR, FFA, ROS, and MDA levels, while restoring HDL-C, GSH, SOD, ATP, and RCR (
Conclusion
Astragali Radix-Puerariae Lobatae Radix compatibility significantly improves insulin resistance in T2DM rats by promoting liver mitochondrial autophagy and restoring autophagic flux via activation of the PINK1/Parkin signaling pathway.