Scopoletin increases glucose uptake through activation of PI3K and AMPK signaling pathway and improves insulin sensitivity in 3T3-L1 cells

Abstract

Coumarins have been shown to reduce blood glucose levels and improve insulin sensitivity in other studies. The purpose of this study was to investigate the effects of scopoletin, which is a type of coumarin family, on glucose uptake in 3T3-L1 cells to test the hypothesis that scopoletin exerts an antidiabetic function on adipocytes. Scopoletin significantly increased glucose uptake, which was associated with increased expression of the plasma membrane glucose transporter type 4 (PM-GLUT4) in 3T3-L1 adipocytes. This increase in PM-GLUT4 expression was promoted by phosphorylation of protein kinase B, activation of phosphatidylinositol-3-kinase (PI3K), and enhanced intracellular glucose uptake. Scopoletin also promoted phosphorylation of adenosine monophosphate–activated protein kinase (AMPK) and enhanced PM-GLUT4 expression. Scopoletin-induced glucose uptake in 3T3-L1 adipocytes was inhibited by treatment with the PI3K inhibitor wortmannin and the AMPK inhibitor compound C. These results suggest that scopoletin has an antidiabetic effect by stimulating GLUT4 translocation to the PM through activation of the PI3K and AMPK pathways in 3T3-L1 adipocytes, thereby upregulating glucose uptake.