Mediation of AMP Kinase in the Increase of Glucose Uptake in L6 Cells Induced by Activation of Imidazoline I-2 Receptors

Abstract

Recent work using radioactive tracer indicates that activation of imidazoline I₂ receptor (I₂R) by guanidinium derivatives may increase the glucose uptake in the skeletal muscle. However, the effect of I₂R activation on nonradioactive glucose uptake is still unknown. The ability of glucose uptake in cultured L6 cells is then determined using 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) as a fluorescence indicator. The changes in 5′-AMP-activated protein kinase (AMPK) expression were also identified by Western blot analysis. In the present study, 2-(2-benzofuranyl)-2-imidazoline (2-BFI) is used to stimulate I₂R while 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) is applied to activate AMPK directly. Both compounds can increase 2-NBDG in L6 cells in a concentration-dependent manner. Meanwhile, compound C at concentrations sufficient to inhibit AMPK blocked this increase of glucose uptake by 2-BFI or AICAR. However, only 2-BFI-induced glucose uptake action was dose-dependently blocked by BU224, a specific I₂R antagonist, in L6 cells. Moreover, AMPK phosphorylation was markedly increased by 2-BFI or AICAR in L6 cells. Similarly, only the effect of 2-BFI was attenuated by BU224 in L6 cells. Thus, we suggest that AMPK is mediated in I₂R activation for increase of glucose uptake in the skeletal muscle cell and I₂R will be a new target for diabetic therapy.

Key words

2-BFI - 5′-AMP-activated protein kinase - BU224 - glucose uptake - L6 cell

• References

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