| dc.description.abstract | Insulin, resistin, endothelin-1 (ET-1), and (-)-epigallocatechin gallate (EGCG) have been reported to regulate obesity and fat accumulation, respectively. This study investigated the pathways involved in EGCG modulation of insulin- and/or ET-1-stimulated glucose uptake in 3T3-L1 and C3H10T1/2 adipocytes. EGCG inhibited insulin and/or ET-1 stimulation of adipocyte glucose uptake in a dose- and time-dependent manner. The concentration of EGCG that decreased the insulin- or ET-1-stimulated glucose uptake by 50%-80% was approximately 5-10 μM for a range of 2 h. The dose-dependent effect of EGCG in suppressing the insulin and ET-1 stimulation of glucose uptake was also observed in 3T3-L1 and C3H10T1/2 preadipocytes, C2C12 myoblast, and H4IIEC3 hepatoma cells. At 10 μM EGCG was more effective than (-)-epicatechin, (-)-epigallocatechin, and (-)-epicatechin-3-gallate. This suggests a catechin type-dependent effect. A putative EGCG receptor [also known as the 67-kilodalton laminin receptor (67LR)] was discovered in lung cancer cells and then identified in fat cells. Pretreatment of adipocytes with 67LR antibody, but not normal rabbit immunoglobulin, prevented the effects of EGCG on insulin- or ET-1-increased glucose uptake in adipocytes. Moreover, pretreatment with the AMP-activated protein kinase (AMPK) inhibitor, such as compound C, but not with the GSH activator, such as N-acetyl-L-cysteine, blocked the anti-insulin and anti-ET-1 effects of EGCG on adipocyte glucose uptake. These data suggest that EGCG exerts its anti-insulin and anti-ET-1 actions on adipocyte glucose uptake via the 67LR and AMPK, but not GSH, pathways. Interestingly, EGCG was found to enhance the anti-insulin effect of resistin on adipocyte glucose uptake, and it reduced the synergistic effects of insulin and ET-1 on adipocyte glucose uptake. As glucose serves as the metabolite to produce one of the precursors of triglycerides, results of this study may possibly support that EGCG modulates hormone-mediated fat content.
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