Astragaloside IV Regulates Insulin Resistance and Inflammatory Response of Adipocytes via Modulating MIR-21/PTEN/PI3K/AKT Signaling

Abstract

Background: The progression of Type 2 Diabetes Mellitus (T2DM) can lead to various complications. Compounds derived from natural products have been found to be effective in com-batting T2DM. This study aimed to investigate the effects of Astragaloside IV (AS-IV) on insulin resistance and the inflammatory response of adipocytes. The study also aimed to determine the downstream signaling pathways involved. Materials and Methods: The glucose consumption of adipocytes was assessed using a glucose assay kit. qRT-PCR, Western blot, and ELISA assays were used to measure mRNA and protein levels. The interaction between miR-21 and PTEN was assessed using a Dual-luciferase reporter assay. Results: The results showed that AS-IV increased glucose consumption and the expression of GLUT-4 in adipocytes with insulin resistance in a concentration-dependent manner. However, AS-IV decreased the protein levels of TNF-α and IL-6 in these cells. Additionally, AS-IV up-regulated miR-21 expression in adipocytes with insulin resistance in a concentration-dependent manner. Fur-thermore, miR-21 overexpression increased glucose consumption and GLUT-4 expression but de-creased TNF-α and IL-6 protein levels in adipocytes. Conversely, miR-21 inhibition attenuated the AS-IV-induced increase in glucose consumption and GLUT-4 expression and the decrease in TNF-α and IL-6 protein levels in adipocytes. MiR-21 also inversely regulated PTEN in adipocytes, and PTEN overexpression had effects similar to miR-21 inhibition in AS-IV-treated adipocytes. Fi-nally, AS-IV up-regulated p-PI3K and p-AKT protein expression in adipocytes, which was atten-uated by miR-21 inhibition. Conclusion: The study concluded that AS-IV attenuated insulin resistance and the inflammatory response in adipocytes. The mechanistic studies indicated that AS-IV modulated the miR-21/PTEN/PI3K/AKT signaling in adipocytes to exert these effects.