Activation of Imidazoline I-2B Receptors by Allantoin to Increase Glucose Uptake into C2C12 Cells

Abstract

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_2BR) by guanidinium derivatives also increases glucose uptake; however, the effect of allantoin on I_2BR 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_2BR to increase glucose uptake into cells, and propose I_2BR as a new target for diabetic therapy.

Key words

allantoin - 5′-AMP-activated protein kinase - BU224 - glucose uptake - imidazoline receptor

• References

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