Stimulatory effect of caffeic acid on α1A-adrenoceptors to increase glucose uptake into cultured C2C12 cells

In an attempt to understand the antihyperglycemic action of caffeic acid, the myoblast C2C12 cells were employed to investigate the glucose uptake in the present study. Caffeic acid enhanced the uptake of radioactive glucose into C2C12 cells in a concentration-dependent manner. Similar effect of phenylephrine on the uptake of radioactive glucose was also observed in C2C12 cells. Prazosin attenuated the action of caffeic acid in a way parallel to the blockade of phenylephrine. Effect of caffeic acid on al-adrenoceptors was further supported by the displacement of [H-3]prazosin binding in C2C12 cells. Moreover, the glucose uptake-increasing action of phenylephrine in C2C12 cells was inhibited by the antagonists of alpha(1A)-adrenoceptors, both tamsulosin and WB 4101, but not by the antagonist of alpha(1B)-adrenoceptors, chlorethylclonidine (CEC). The presence of alpha(1A)-adrenoceptors in C2C12 cells can thus be considered. Similar inhibition of the action of caffeic acid was also obtained in C2C12 cells co-incubating these antagonists. An activation of alpha(1A)-adrenoceptors seems responsible for the action of caffeic acid in C2C12 cells. In the presence of U73312, the specific inhibitor of phospholipase C, caffeic acid-stimulated uptake of radioactive glucose into C2C12 cells was reduced in a concentration-dependent manner and it was not affected by U73343, the negative control of U73312. Moreover, chelerythrine and GF 109203X diminished the action of caffeic acid at concentrations sufficient to inhibit protein kinase C. Therefore, the obtained data suggest that an activation of alpha(1A)-adrenoceptors in C2C12 cells by caffeic acid may increase the glucose uptake via phospholipase C-protein kinase C pathway.