Astragalus polysaccharides attenuates TNF-α-induced insulin resistance via suppression of miR-721 and activation of PPAR-γ and PI3K/AKT in 3T3-L1 adipocytes.

Insulin resistance is associated with obesity and type 2 diabetes. The aim of this study was to explore the mechanism of how Astragalus Polysaccharides (APS) improves insulin resistance in 3T3-L1 adipocytes. A cell culture model of insulin resistance was established in mature 3T3-L1 adipocytes by treating them with TNF-α, high glucose and insulin. Glucose uptake levels were detected in each group. To determine the mechanism by which APS improves insulin resistance in 3T3-L1 adipocytes, qRT-PCR was used to detect the expression of miR-721, and Western blots were used to detect the expression or activity of PPAR-γ, PAKT, PI3K, AKT, and GLUT4. Immunostaining was used to detect the expression of GLUT4. We successfully madea model of insulin resistance in mature 3T3-L1 adipocytes. APS increased glucose uptake levels in insulin-resistant adipocytes in a dose- and time-dependent manner, and also increased insulin sensitivity. APS suppressed miR-721 with its target gene PPAR-γ in a dose-dependent manner. miR-721 or PPAR inhibitor T0070907 inhibited the expressions of PPAR-γ, pAKT, and GLUT4 and also reduced glucose accumulation. APS attenuated these miR-721- and PPAR-γ-induced changes. APS increased insulin sensitivity by attenuating the effects of miR-721. The PI3K inhibitor wortmannin reduced the APS-increased pAKT, glucose uptake, and GLUT4 levels, and also reduced those levels in the presence of insulin with or without APS. Taken together, our findings suggest that APS promotes glucose uptake and increases insulin sensitivity in 3T3-L1 adipocytes and may involve the miR-721-PPAR-γ-PI3K/AKT-GLUT4 signaling pathway. These might be new therapeutic targets for treating insulin resistance in obesity and diabetes.