Green tea (−)‐epigallocatechin gallate inhibits IGF‐I and IGF‐II stimulation of glucose uptake in 3T3‐L1 adipocytes

Abstract

ObjectiveThis study investigated the pathways involved in EGCG modulation of IGF‐stimulated glucose uptake in 3T3‐L1 adipocytes.MethodsGlucose uptake was assayed to measure the uptake of 3H‐2‐deoxyglucose. Western blot analysis was performed to measure levels of Glucose transporters (GLUTs) and IGF signaling molecules.ResultsEGCG inhibited IGF‐I and IGF‐II stimulation of adipocyte glucose uptake in dose‐ and time‐dependent manners. Treatment with 20 μM EGCG for 2 h significantly decreased IGF‐I‐ and IGF‐II‐stimulated glucose uptake by 59% and 64%, respectively. The EGCG receptor [also known as the 67‐kDa laminin receptor (67LR)] was discovered in fat cells. Pretreatment of adipocytes with a 67LR antibody, but not normal rabbit immunoglobulin, prevented the effects of EGCG on IGF‐increased glucose uptake. Moreover, pretreatment with an AMP‐activated protein kinase (AMPK) inhibitor, such as compound C, but not with a glutathione activator, such as N‐acetyl‐L‐cysteine, blocked the anti‐IGF effect of EGCG on adipocyte glucose uptake. Further analysis for subcellular fractions indicated that EGCG decreased the IGF‐induced increases in the GLUT4 translocation from the cytosol to the plasma membrane and that EGCG had no effects on the level of GLUT1 translocation and total amounts of GLUT‐1 and GLUT‐4 proteins. In addition, EGCG suppressed the IGF‐stimulated phosphorylation of PKCζ/λ, but not Akt or ERK, proteins.ConclusionsThese results suggest that EGCG inhibits IGF‐I and IGF‐II stimulation of 3T3‐L1 adipocyte glucose uptake through downregulated GLUT‐4 translocation and IGF signaling and through 67LR‐ and AMPK‐dependent pathways.