Stimulatory effect of caffeic acid on α_1A-adrenoceptors to increase glucose uptake into cultured C₂C₁₂ cells

Abstract.

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 α₁-adrenoceptors was further supported by the displacement of [³H]prazosin binding in C₂C₁₂ cells. Moreover, the glucose uptake-increasing action of phenylephrine in C₂C₁₂ cells was inhibited by the antagonists of α_1A-adrenoceptors, both tamsulosin and WB 4101, but not by the antagonist of α_1B-adrenoceptors, chlorethylclonidine (CEC). The presence of α_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 α_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 α_1A-adrenoceptors in C₂C₁₂ cells by caffeic acid may increase the glucose uptake via phospholipase C-protein kinase C pathway.