Fuzhu jiangtang granules combined with metformin reduces insulin resistance in skeletal muscle of diabetic rats via PI3K/Akt signaling

Context: Fuzhu Jiangtang Granules (FJG) are a traditional Chinese used in the treatment of diabetes mellitus. However, the antidiabetic mechanism of FJG is not clear. Objective: This study evaluates and determines the antidiabetic mechanism of FJG using a Zucker diabetic fatty (ZDF) rat model. Materials and methods: ZDF (fa/fa) rats were divided into four groups (n = 6): diabetes mellitus (DM), metformin (Met, 0.134 g/kg b.w./day), FJG (0.64 g/kg b.w./day), and combination (Com, 0.134 g/kg b.w./day of Met and 0.64 g/kg b.w./day of FJG). Six ZDF (fa/+) rats served as a normal control. After 6 weeks, biochemical parameters gene and protein expression were detected. Results: The FBG, bodyweight, triglyceride (TG), total cholesterol (TC), free fatty acid (FFA), insulin levels, and HOMA-IR were lower in the FJG than in the DM group (p < 0.05, p < 0.01). In an oral glucose tolerance test, the AUC in the FJG group was significantly lower (p < 0.01). The levels of superoxide dismutase and catalase were higher in the FJG than in the DM group (p < 0.01); the malondialdehyde content and TNF-α were significantly decreased in the FJG group (p < 0.01). FJG increased the mRNA expression of IR and GLUT4 significantly (p < 0.05, p < 0.01). The protein levels of IR, p-IRS1 tyr989, m-PI3Kp85, p-Akt and GLUT4 were increased in the FJG (p < 0.05, p < 0.01), but the protein levels of p-IRS1 ser1101/612/307 were significantly decreased in the JG group (p < 0.01). Discussion and conclusions: The antidiabetic mechanism of FJG may be related to regulation of the insulin-signaling pathway in skeletal muscle. These aspects require further research.