Activation of imidazoline I2B receptors is linked with AMP kinase pathway to increase glucose uptake in cultured C2C12 cells

Guanidine, the active ingredient extracted from Galega officinalis, is introduced as a ligand for imidazoline I2 receptor (I2R) because guanidine decreased plasma glucose via an activation of I2BR to increase glucose uptake into skeletal muscle isolated from Wistar rats. However, the signals for this action of guanidine remained obscure. In the present study, we used the cultured skeletal muscle fibroblast named C2C12 cell line to investigate this point. We found that guanidine increased the phosphorylation of AMP-activated protein kinase (AMPK) in addition to the higher of glucose transporter GLUT4 expression and glucose uptake. These effects of guanidine were blocked by the pretreatment with I2R antagonist BU224 but not by the blockade of I2AR amiloride. Moreover, compound C at concentrations sufficient to inhibit AMPK blocked the guanidine-induced glucose uptake and GLUT4 protein level. These results suggested that guanidine increases glucose uptake via an activation of I2BR through AMPK activation in skeletal muscle cell; this view has not been mentioned before.