dc.description.abstract | This study investigated the possible mechanism involved in EGCG modulation of ET-1-stimulated glucose uptake in 3T3-L1 adipocytes. We found that pretreatment with the PI3K inhibitors, such as LY294002 and wortmannin, inhibited EGCG-induced decreases on the acutely ET-1 stimulated glucose uptake in adipocytes. However, none of the ERK/MAPK inhibitors, such as PD98059 and U0126, significantly blocked the anti-ET-1 effects of EGCG on adipocyte glucose uptake. These data suggest that PI3K activation is necessary for the effects of EGCG on the acutely ET-1-stimulated glucose uptake in adipocytes. Interestingly, we observed that pretreatment with the JAK2/STAT3 inhibitors, such as AG490(50 µM ), increased the basal glucose uptake and the ET-1-dependent glucose uptake, suggesting the JAK2/STAT3-dependent effect of EGCG. The EGCG receptor [also known as the 67-kDa laminin receptor (67LR)] was identified in fat cells. Pretreatment of adipocytes with 67LR antibody, but not normal rabbit immunoglobulin, prevented the effects of EGCG on ET-1-induced glucose uptake in adipocytes. These data suggest that EGCG exerts its anti-ET-1 actions on adipocyte glucose uptake via the 67LR. However, NAC(an antioxidant) acutely increased the basal glucose uptake and ET-1 stimulated glucose uptake, indicating that NAC possibly affected glucose uptake by suppressing not only the ET-1-dependent ROS production but also the ET-1-independent ROS production. Pretreatment with the AMPK inhibitor, such as compound C, blocked the anti-ET-1 effects of EGCG on adipocyte glucose uptake, and prevented the effects of EGCG on the chronically ET-1-stimulated GLUT-1 protein expression. This suggests that EGCG inhibits the chronically ET-1 action on adipocyte glucose uptake through the activation of AMPK pathway that results in alterations of GLUT-1 protein expression. Results of this study may help understand the mechanism of how green tea EGCG modulates hormone-mediated obesity. | en_US |