2'-benzyloxychalcone derivatives stimulate glucose uptake in 3T3-L1 adipocytes.
By a cell-based glucose uptake screening assay, a chalcone derivative, 3-nitro-2'-benzyloxychalcone (compound 1) was identified. Compound 1 stimulated glucose uptake and potentiated insulin-stimulated glucose uptake in a concentration-dependent manner in 3T3-L1 adipocytes. When cells were treated with various concentrations of insulin in the presence of compound 1, marked enhancement of insulin-stimulated glucose uptake was observed at each concentration, suggesting that the compound might function as an insulin sensitizer. Preliminary study on the structure-activity relationships revealed that two aromatic benzene rings tolerated several substituents, but substitution by acidic or highly polar groups abolished the activity. Among several chalcone derivatives, 4-chloro-2'-benzyloxychalcone (compound 8) showed the highest level of activity. Compound 8-stimulated glucose uptake was almost completely inhibited by wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). These results suggest that the action of chalcone derivatives is mediated via a pathway involving PI3K.
Kamei
Reiko
R
Daiichi Suntory Biomedical Research Co. LTD, 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, 618-8513 Osaka, Japan.
Kadokura
Michinori
M
Kitagawa
Yoshinori
Y
Hazeki
Osamu
O
Oikawa
Shinzo
S
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002599:Chalcone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D047188:Chalcones; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D013329:Structure-Activity Relationship
C476699:3-nitro-2'-benzyloxychalcone; D047188:Chalcones; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495693:Slc2a4 protein, mouse; D002599:Chalcone; D005947:Glucose