Caffeic acid methyl and ethyl esters induce the translocation of glucose transporter GLUT4 in cultured skeletal muscle cells

Abstract

Derivatives of caffeic acid (CA) are widely distributed in the plant kingdom. In a previous study, CA methyl ester (CAME) and CA ethyl ester (CAEE) were reported to potently stimulate glucose uptake in cultured C2C12 skeletal muscle cells. In the present study, we investigated the effect of these compounds on the translocation of insulin-sensitive glucose transporter GLUT4 in cultured L6-GLUT4myc cells. Levels of GLUT4myc at the cell surface were measured by O-phenylenediamine dihydrochloride (OPD) assay. The effects of CAME and CAEE on insulin and AMPK signaling pathways as well as on GLUT4 content were also assessed by western immunoblot. Both compounds significantly increased glucose uptake and GLUT4 translocation to the cell membrane of L6-GLUT4myc cells. Moreover, the two compounds increased phosphorylation of AMPK and increased GLUT4 content. CAME and CAEE may hence improve glucose uptake in L6 cells by promoting GLUT4 expression and translocation through an insulin-independent mechanism involving AMPK. The results of the present study suggest that CAME and CAEE may have therapeutic potential to counter the hyperglycemia of diabetes.