Ellagic Acid Stimulates Glucose Transport in Adipocytes and Muscles through AMPK Mediated Pathway

Glucose transporter 4 (GLUT4) plays a pivotal role in maintaining whole body glucose homeostasis by mediating insulin responsive glucose transport into adipocytes and skeletal muscles. This is achieved through translocation of GLUT4 from an intracellular pool to the cell surface and certain compounds may enhance this process. In the present study we have shown that ellagic acid, a plant polyphenol, can stimulate glucose uptake activity in both 3T3-L1 adipocytes and C2C12 myotubes by inducing GLUT4 translocation. Unlike insulin, ellagic acid did not stimulate the Ser473 phosphorylation and activation of Akt. However, it was found to induce AMP-activated protein kinase (AMPK) activation in both cell lines. Analyzing the downstream mechanism suggested an absence of involvement of Rab GAP AS160 in ellagic acid induced GLUT4 translocation. Further studies revealed that ellagic acid stimulated glucose transport occurs though a mechanism involving extracellular signal-regulated kinase (ERK1/2) and atypical PKC zeta/lambda (aPKC zeta/lambda) activation.