RESUMEN
Allantoin, an active principle of the yam, belongs to the group of guanidinium derivatives and has been reported to lower plasma glucose in diabetic animals. Recent evidence indicates that activation of the imidazoline I(2B) receptor (I(2B)R) by guanidinium derivatives also increases glucose uptake; however, the effect of allantoin on I(2B)R is still unknown. Glucose uptake into cultured C2C12 cells was determined using 2-[¹4C]-deoxy-D-glucose as a tracer. The changes in 5'-AMP-activated protein kinase (AMPK) expression were also identified by Western blotting analysis. The allantoin-induced glucose uptake action was dose-dependently blocked by BU224, a specific I2R antagonist, in C2C12 cells. Moreover, AMPK phosphorylation by allantoin was found to be dose-dependently increased in C2C12 cells using AICAR treatment as a reference. In addition, both actions of allantoin, the increases in glucose uptake and AMPK phosphorylation, were dose-dependently attenuated by amiloride in C2C12 cells. Moreover, compound C at concentrations sufficient to inhibit AMPK blocked the allantoin-induced glucose uptake and AMPK phosphorylation. Thus, we suggest that allantoin can activate I(2B)R to increase glucose uptake into cells, and propose I(2B)R as a new target for diabetic therapy.