Prenylated chalcones 4-hydroxyderricin and xanthoangelol stimulate glucose uptake in skeletal muscle cells by inducing GLUT4 translocation

Scope: Glucose uptake in skeletal muscle is crucial for glucose homeostasis. Methods and results: Insulin and muscle contraction increase glucose uptake accompanied by the translocation of glucose transporter (GLUT) 4. In a search for promising foods, which can increase glucose uptake in skeletal muscle, we screened for active polyphenols by assaying for uptake of 2-deoxyglucose (2DG) in rat L6 muscle cells. Among 37 compounds, 4-hydroxyderricin and xanthoangelol, prenylated chalcones abundant in Ashitaba (Angelica keiskei Koidzumi, family Apiaceae), significantly increased 2DG uptake in L6 cells by 1.9-fold at 10 mu M, compared with the level in DMSO-treated control cells. Next, we investigated the effect of these chalcones on the translocation of GLUT4 and its underlying mechanisms. The chalcones increased the GLUT4 level in the plasma membrane of L6 cells, but activated neither protein kinase C zeta/lambda, Akt, nor adenosine monophosphate-activated protein kinase, all of which regulate the GLUT4 translocation. Interestingly, the oral administration of a titrated chalcone-enriched Ashitaba extract containing 150.6 mg/g (dry base) of 4-hydroxyderricin and 146.0 mg/g (dry base) of xanthoangelol suppressed acute hyperglycemia in oral glucose tolerance tests of mice. Conclusions: Ashitaba is a promising functional food for the maintenance of the blood glucose level by inducing skeletal muscle-associated glucose uptake.