title: Green tea epigallocatechin gallate inhibits insulin stimulation of adipocyte glucose uptake via the 67-kilodalton laminin receptor and AMP-activated protein kinase pathways.
abstract: Insulin and (-)-epigallocatechin gallate (EGCG) are reported to regulate obesity and fat accumulation, respectively. This study investigated the pathways involved in EGCG modulation of insulin-stimulated glucose uptake in 3T3-L1 and C3H10T1/2 adipocytes. EGCG inhibited insulin stimulation of adipocyte glucose uptake in a dose- and time-dependent manner. The concentration of EGCG that decreased insulin-stimulated glucose uptake by 50-60% was approximately 5-10 µM for a period of 2 h. At 10 µM, EGCG and gallic acid were more effective than (-)-epicatechin, (-)-epigallocatechin, and (-)-epicatechin 3-gallate. We identified the EGCG receptor [also known as the 67-kDa laminin receptor (67LR)] in fat cells and extended the findings for this study to clarify whether EGCG-induced changes in insulin-stimulated glucose uptake in adipocytes could be mediated through the 67LR. Pretreatment of adipocytes with a 67LR antibody, but not normal rabbit immunoglobulin, prevented the effects of EGCG on insulin-increased glucose uptake. This suggests that the 67LR mediates the effect of EGCG on insulin-stimulated glucose uptake in adipocytes. Moreover, pretreatment with an AMP-activated protein kinase (AMPK) inhibitor, such as compound C, but not with a glutathione (GSH) activator, such as N-acetyl-L-cysteine (NAC), blocked the antiinsulin effect of EGCG on adipocyte glucose uptake. These data suggest that EGCG exerts its anti-insulin action on adipocyte glucose uptake via the AMPK, but not the GSH, pathway. The results of this study possibly support that EGCG mediates fat content.
authors.affiliation: Department of Life Sciences, National Central University, Jhongli, Taiwan.
authors.forename: Chi-Fen
authors.initials: CF
authors.lastname: Hsieh
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Tsuei
authors.forename: Chi-Wei
authors.initials: CW
authors.lastname: Liu
authors.forename: Chung-Cheng
authors.initials: CC
authors.lastname: Kao
authors.forename: Li-Jane
authors.initials: LJ
authors.lastname: Shih
authors.forename: Low-Tone
authors.initials: LT
authors.lastname: Ho
authors.forename: Liang-Yi
authors.initials: LY
authors.lastname: Wu
authors.forename: Chi-Peng
authors.initials: CP
authors.lastname: Wu
authors.forename: Pei-Hua
authors.initials: PH
authors.lastname: Tsai
authors.forename: Hsin-Huei
authors.initials: HH
authors.lastname: Chang
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Ku
authors.forename: Yung-Hsi
authors.initials: YH
authors.lastname: Kao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D041681:NIH 3T3 Cells; D017474:Receptors, Laminin / Q000502:physiology*; D013662:Tea / Q000737:chemistry*
chemical_list: D007328:Insulin; D017474:Receptors, Laminin; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D055372:AMP-Activated Protein Kinases; D005947:Glucose