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.