AMP-Activated Protein Kinase Activation by Adrenoceptors in L6 Skeletal Muscle Cells

Abstract

AMP-activated protein kinase (AMPK), which functions as a sensor of cellular energy homeostasis, was phosphorylated after norepinephrine stimulation in L6 skeletal muscle cells. This effect was mediated by α₁-adrenoceptors, with no stimulatory effects due to interactions at α₂- or β-adrenoceptors. α₁-Adrenoceptors are Gq-coupled receptors, and calcium but not phorbol esters could mimic the effect of α₁-adrenergic stimulation; and we show that protein kinase C is not involved as an upstream signal to AMPK by α₁-adrenergic stimulation and that the AMP-to-ATP ratio is unaltered after α₁-adrenergic stimulation. We further show that glucose uptake mediated by α₁- but not by β-adrenoceptors can be inhibited by AMPK inhibition. Acetyl-CoA carboxylase (ACC) is phosphorylated at Ser218 by AMPK, and α₁- but not β-adrenoceptor stimulation results in phosphorylation of ACC at this residue. These results suggest a novel pathway where α₁-adrenoceptor activation, independent of protein kinase C, leads to activation of AMPK in skeletal muscle, which contributes to α₁-adrenoceptor–mediated increases in glucose uptake.