AMP-Activated protein kinase activation by adrenoceptors in L6 skeletal muscle cells: mediation by adrenoceptors causing glucose uptake

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 1-adrenoceptors, with no stimulatory effects due to interactions at 2- or f-adrenoceptors. 1-Adrenoceptors are Gq-coupled receptors, and calcium but not phorbol esters could mimic the effect of 1-adrenergic stimulation; and we show that protein kinase C is not involved as an upstream signal to AMPK by 1-adrenergic stimulation and that the AMP-to-ATP ratio is unaltered after 1-adrenergic stimulation. We further show that glucose uptake mediated by 1- but not by f-adrenoceptors can be inhibited by AMPK inhibition. Acetyl-CoA carboxylase (ACC) is phosphorylated at Ser218 by AMPK, and 1- but not f-adrenoceptor stimulation results in phosphorylation of ACC at this residue. These results suggest a novel pathway where 1-adrenoceptor activation, independent of protein kinase C, leads to activation of AMPK in skeletal muscle, which contributes to 1-adrenoceptor\u96mediated increases in glucose uptake