ArticleDiabetologia2007
Beta(2)-Adrenergic activation increases glycogen synthesis in L6 skeletal muscle cells through a signalling pathway independent of cyclic AMP.
Article in Diabetologia, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 36 citations in OpenAlex.
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- Gαi2 regulates the adult myogenesis of masticatory muscle satellite cells.Journal of cellular and molecular medicine · 2023Article
- Inhibition of signaling downstream of beta-2 adrenoceptor by propranolol in prostate cancer cells.The Prostate · 2023Article
- Alpha-ketoglutarate partially alleviates effects of high-fat high-fructose diet in mouse muscle.EXCLI journal · 2023Article
- Beta 2 adrenergic receptor and mu opioid receptor interact to potentiate the aggressiveness of human breast cancer cell by activating the glycogen synthase kinase 3 signaling.Breast cancer research : BCR · 2022Article
- Adrenergic and Glucocorticoid Receptors in the Pulmonary Health Effects of Air Pollution.Toxics · 2021Review
- Insulin/IGF1 signalling mediates the effects of βJournal of cachexia, sarcopenia and muscle · 2019Article
- β2-adrenoceptor agonists can both stimulate and inhibit glucose uptake in mouse soleus muscle through ligand-directed signalling.Naunyn-Schmiedeberg's archives of pharmacology · 2013Article
- Nr4a1 is required for fasting-induced down-regulation of Pparγ2 in white adipose tissue.Molecular endocrinology (Baltimore, Md.) · 2013Article
- β(2)-Adrenoceptors increase translocation of GLUT4 via GPCR kinase sites in the receptor C-terminal tail.British journal of pharmacology · 2012Article
- Article
- Metabolic responses to BRL37344 and clenbuterol in soleus muscle and C2C12 cells via different atypical pharmacologies and beta2-adrenoceptor mechanisms.British journal of pharmacology · 2008Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisIn skeletal muscle, the storage of glycogen by insulin is regulated by glycogen synthase, which is regulated by glycogen synthase kinase 3 (GSK3). Here we examined whether adrenergic receptor activation, which can increase glucose uptake, regulates glycogen synthesis in L6 skeletal muscle cells.
methodsWe used L6 cells and measured glycogen synthesis (as incorporation of D: -[U-(14)C]glucose into glycogen) and GSK3 phosphorylation following adrenergic activation.
resultsInsulin (negative logarithm of median effective concentration [pEC(50)] 8.2 +/- 0.3) and the beta-adrenergic agonist isoprenaline (pEC(50) 7.5 +/- 0.3) induced a twofold increase in glycogen synthesis in a concentration-dependent manner. The alpha(1)-adrenergic agonist cirazoline and alpha(2)-adrenergic agonist clonidine had no effect. Both insulin and isoprenaline phosphorylated GSK3. The beta-adrenergic effect on glycogen synthesis is mediated by beta(2)-adrenoceptors and not beta(1)-/beta(3)-adrenoceptors, and was not mimicked by 8-bromo-cyclic AMP or cholera toxin, and also was insensitive to pertussis toxin, indicating no involvement of cyclic AMP or inhibitory G-protein (G(i)) signalling in the beta(2)-adrenergic effect on glycogen synthesis. 12-O-tetra-decanoylphorbol-13-acetate (TPA) increased glycogen synthesis 2.5-fold and phosphorylated GSK3 fourfold. Inhibition of protein kinase C (PKC) isoforms with 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrollo(3,4-c)-carbazole (Gö6976; inhibits conventional and novel PKCs) or 2-[1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl)maleimide (Gö6983; inhibits conventional, novel and atypical PKCs) inhibited the stimulatory TPA effect, but did not significantly inhibit glycogen synthesis mediated by insulin or isoprenaline. Inhibition of phosphatidylinositol 3-kinase (PI3K) with wortmannin inhibited the effects of insulin and isoprenaline on glycogen synthesis. CONCLUSIONS/
interpretationThese results demonstrate that in L6 skeletal muscle cells adrenergic stimulation through beta(2)-adrenoceptors, but not involving cyclic AMP or G(i), activates a PI3K pathway that stimulates glycogen synthesis through GSK3.
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