β2-Adrenergic activation increases glycogen synthesis in L6 skeletal muscle cells through a signalling pathway independent of cyclic AMP
| Autor: | Dana S. Hutchinson, Tore Bengtsson, Daniel L. Yamamoto |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism AMP-Activated Protein Kinases Protein Serine-Threonine Kinases Cell Line Glycogen debranching enzyme Glycogen Synthase Kinase 3 Phosphatidylinositol 3-Kinases chemistry.chemical_compound Glycogen phosphorylase Multienzyme Complexes Internal medicine Cyclic AMP Internal Medicine Glycogen branching enzyme medicine Animals Insulin Phosphorylation Muscle Skeletal Phosphorylase kinase Glycogen synthase Protein Kinase Inhibitors GSK3B Phosphoinositide-3 Kinase Inhibitors biology Glycogen Chemistry Isoproterenol Adrenergic beta-Agonists Rats Androstadienes Glucose Endocrinology Glycogenesis biology.protein Receptors Adrenergic beta-2 Wortmannin Signal Transduction |
| Zdroj: | Diabetologia. 50:158-167 |
| ISSN: | 1432-0428 0012-186X |
| Popis: | In 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.We used L6 cells and measured glycogen synthesis (as incorporation of D: -[U-(14)C]glucose into glycogen) and GSK3 phosphorylation following adrenergic activation.Insulin (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.These 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. |
| Databáze: | OpenAIRE |
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