Hutchinson Dana S, Bengtsson Tore
Department of Physiology, The Wenner-Gren Institute, Stockholm University, SE 10691 Stockholm, Sweden.
Diabetes. 2006 Mar;55(3):682-90. doi: 10.2337/diabetes.55.03.06.db05-0901.
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 alpha1-adrenoceptors, with no stimulatory effects due to interactions at alpha2- or beta-adrenoceptors. Alpha1-adrenoceptors are Gq-coupled receptors, and calcium but not phorbol esters could mimic the effect of alpha1-adrenergic stimulation; and we show that protein kinase C is not involved as an upstream signal to AMPK by alpha1-adrenergic stimulation and that the AMP-to-ATP ratio is unaltered after alpha1-adrenergic stimulation. We further show that glucose uptake mediated by alpha1- but not by beta-adrenoceptors can be inhibited by AMPK inhibition. Acetyl-CoA carboxylase (ACC) is phosphorylated at Ser218 by AMPK, and alpha1- but not beta-adrenoceptor stimulation results in phosphorylation of ACC at this residue. These results suggest a novel pathway where alpha1-adrenoceptor activation, independent of protein kinase C, leads to activation of AMPK in skeletal muscle, which contributes to alpha1-adrenoceptor-mediated increases in glucose uptake.
AMP激活的蛋白激酶（AMPK）作为细胞能量稳态的传感器，在L6骨骼肌细胞中去甲肾上腺素刺激后被磷酸化。这种作用由α1肾上腺素能受体介导，α2或β肾上腺素能受体相互作用无刺激作用。α1肾上腺素能受体是Gq偶联受体，钙而非佛波酯可模拟α1肾上腺素能刺激的作用；并且我们表明蛋白激酶C不参与α1肾上腺素能刺激作为AMPK的上游信号，且α1肾上腺素能刺激后AMP与ATP的比值未改变。我们进一步表明，α1而非β肾上腺素能受体介导的葡萄糖摄取可被AMPK抑制所抑制。乙酰辅酶A羧化酶（ACC）在Ser218位点被AMPK磷酸化，α1而非β肾上腺素能受体刺激导致该残基处的ACC磷酸化。这些结果提示了一条新途径，即α1肾上腺素能受体激活，不依赖蛋白激酶C，导致骨骼肌中AMPK激活，这有助于α1肾上腺素能受体介导的葡萄糖摄取增加。
