A new chromanone isolated from Portulaca oleracea L. increases glucose uptake by stimulating GLUT4 translocation to the plasma membrane in 3T3-L1 adipocytes

Abstract

Three homoisoflavonoids and one dimethoxychalcone from Portulaca oleracea L. were isolated using bioassay-guided fractionation and HPLC. Among the compounds 1-4, (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone (compound 3) had the most effect on glucose uptake in the adipocytes. We investigated how (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone contributed to increase glucose uptake in 3T3-L1 adipocytes. Levels of the glucose transporters GLUT-4, as well as glucose uptake, and key proteins of the insulin pathway, namely PI3K/AKT and AMPK pathway are analyzed using glucose uptake assay and western blot analysis. Our results show that (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone significantly increased glucose uptake by stimulating translocation of GLUT4 to the plasma membrane in 3T3-L1 adipocytes. High levels of expression of GLUT4 in the plasma membrane resulted from IRS-1 phosphorylation, PI3K activation, Akt phosphorylation and phosphorylation of AMPK, resulting in increased glucose uptake by the cells. The increase in glucose uptake due to (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone was significantly inhibited by the PI3K inhibitor and the AMPK inhibitor in 3T3-L1 adipocytes. These findings suggest that (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone may increase glucose uptake by stimulating GLUT4 translocation to the plasma membrane via activating the PI3K/Akt and AMPK pathways in 3T3-L1 adipocytes.

Keywords: 3T3-L1 adipocytes; AMPK; Diabetes; Glucose uptake; Homoisoflavonoid; PI3K/Akt.