Ellagic acid stimulates glucose transport in 3T3‐L1 adipocytes and C2C12 myotubes by AMP activated protein kinase mediated pathway

Abstract

Glucose Transporter 4 (GLUT4) is an insulin sensitive glucose transporter isoform predominantly expressed in adipocytes and skeletal muscle. It is largely confined to intracellular compartments in an unstimulated state and undergoes translocation to the cell surface in insulin dependent and independent manner to facilitate the bulk uptake of glucose. The present work aims at finding novel modulators of GLUT4 translocation and glucose transport from natural products. Our results show that ellagic acid, a plant polyphenol, can stimulate glucose uptake in 3T3‐L1 adipocytes and C2C12 myotubes in a dose dependent manner. GLUT4 translocation assay in 3T3‐L1 cells stably transfected with myc‐GLUT4‐GFP chimera has shown a corresponding increase in GLUT4 translocation upon ellagic acid treatment. Unlike insulin, ellagic acid did not stimulate the Ser‐473 phosphorylation and activation of Akt. However, the compound was found to significantly activate AMP activated protein kinase (AMPK) which is another major pathway involved in GLUT4 translocation. Ellagic acid stimulated glucose transport was inhibited by pretreatment with Compound C, an AMPK inhibitor. These findings suggest that ellagic acid mediated GLUT4 translocation occurs though a mechanism distinct from that of insulin and involves AMPK activation. This work was supported by a grant from Council of Scientific and Industrial Research, Govt. of India.