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.

Kinsenoside-mediated lipolysis through an AMPK-dependent pathway in C3H10T1/2 adipocytes

“…Several studies have investigated whether natural products inhibit adipogenesis or enhance lipolysis to reduce the amount of adipose tissue. A major component of flavonoids in green tea, (−)-epigallocatechin gallate (EGCG), was shown to significantly reduce insulin-stimulated glucose uptake through the 67LR, known as the EGCG receptor, and AMPK pathways at 5-10 μM in 3T3-L1 and C3H10T1/2 adipocytes (Hsieh et al 2010). Other natural compounds, such as genistein in soy, xanthohumol in beer hops, resveratrol in grapes, and curcumin in turmeric, were reported to exhibit adipogenesis inhibition activities by reducing peroxisome proliferator-activated receptor gamma (PPARγ ) expression and/or activating AMPK in adipocytes (Andersen et al 2010).…”

Epigallocatechin-3-gallate prevents TNF-α-induced NF-κB activation thereby upregulating ABCA1 via the Nrf2/Keap1 pathway in macrophage foam cells

“…It is reported that a 67-kDa laminin receptor (67LR), as the cell surface EGCG receptor, may be involved in mediating these actions of EGCG (22)(23)(24)(25). Moreover, EGCG is also believed to exert an Epigallocatechin-3-gallate prevents TNF-α-induced NF-κB activation thereby upregulating ABCA1 via the Nrf2/Keap1 pathway in macrophage foam cells anti-atherosclerotic effect via anti-inflammatory and metabolic regulation activities (26,27).…”

Investigation into the mechanism of (−)-epigallocatechin-3-gallate-induced precipitation of insulin

“…Though the interactions between EGCG and insulin have been extensively studied in vivo [22][23][24][25], the molecular interactions between EGCG and insulin are still unclear. In this work, we have found that EGCG at concentrations of 1-5 mM induces insulin to aggregate into reversible globular precipitate.…”