AMP-activated protein kinase activation by adrenoceptors in L6 skeletal muscle cells: mediation by alpha1-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 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.
Hutchinson
Dana S
DS
Department of Physiology, The Wenner-Gren Institute, Stockholm University, SE 10691 Stockholm, Sweden.
Bengtsson
Tore
T
D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000502:physiology; D006224:Cricetinae; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*; D012265:Ribonucleotides / Q000494:pharmacology
D007328:Insulin; D009097:Multienzyme Complexes; D018342:Receptors, Adrenergic, beta-1; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; C526181:PRKAA2 protein, human; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human; D000103:Acetyl-CoA Carboxylase; C031143:AICA ribonucleotide; D005947:Glucose; D002118:Calcium