α1A-Adrenoceptors Activate Glucose Uptake in L6 Muscle Cells through a Phospholipase C-, Phosphatidylinositol-3 Kinase-, and Atypical Protein Kinase C-Dependent Pathway
| Autor: | Dana S. Hutchinson, Tore Bengtsson |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Agonist
medicine.medical_specialty medicine.drug_class medicine.medical_treatment Glucose uptake Adrenergic beta-Antagonists Muscle Fibers Skeletal Protein Serine-Threonine Kinases Biology p38 Mitogen-Activated Protein Kinases Cell Line Phenylephrine Phosphatidylinositol 3-Kinases chemistry.chemical_compound Endocrinology Proto-Oncogene Proteins Receptors Adrenergic alpha-1 Internal medicine medicine Animals Hypoglycemic Agents Insulin RNA Messenger Kinase activity Extracellular Signal-Regulated MAP Kinases Protein kinase B Adrenergic alpha-Antagonists Protein Kinase C Protein kinase C Phospholipase C Imidazoles Isoproterenol Prazosin Adrenergic beta-Agonists Propranolol Cirazoline Rats Glucose chemistry Type C Phospholipases Carcinogens Tetradecanoylphorbol Acetate Adrenergic alpha-Agonists Proto-Oncogene Proteins c-akt |
| Zdroj: | Endocrinology. 146:901-912 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | The role of α1-adrenoceptor activation on glucose uptake in L6 cells was investigated. The α1-adrenoceptor agonist phenylephrine [pEC50 (−log10 EC50), 5.27 ± 0.30] or cirazoline (pEC50, 5.00 ± 0.23) increased glucose uptake in a concentration-dependent manner, as did insulin (pEC50, 7.16 ± 0.21). The α2-adrenoceptor agonist clonidine was without any stimulatory effect on glucose uptake. The stimulatory effect of cirazoline was inhibited by the α1-adrenoceptor antagonist prazosin, but not by the β-adrenoceptor antagonist propranolol. RT-PCR showed that the α1A-adrenoceptor was the sole α1-adrenoceptor subtype expressed in L6 cells. Cirazoline- or insulin-mediated glucose uptake was inhibited by the phosphatidylinositol-3 kinase inhibitor LY294002, suggesting a possible interaction between the α1-adrenoceptor and insulin pathways. Cirazoline or insulin stimulated phosphatidylinositol-3 kinase activity, but α1-adrenoceptor activation did not phosphorylate Akt. Both cirazoline- and insulin-mediated glucose uptake were inhibited by protein kinase C (PKC), phospholipase C, and p38 kinase inhibitors, but not by Erk1/2 inhibitors (despite both treatments being able to phosphorylate Erk1/2). Insulin and cirazoline were able to activate and phosphorylate p38 kinase. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate and the calcium ionophore A23187 produced significant increases in glucose uptake, indicating roles for PKC and calcium in glucose uptake. Down-regulation of conventional PKC isoforms inhibited glucose uptake mediated by 12-O-tetradecanoylphorbol-13-acetate, but not by insulin or cirazoline. This study demonstrates that α1-adrenoceptors mediate increases in glucose uptake in L6 muscle cells. This effect appears to be related to activation of phospholipase C, phosphatidylinositol-3 kinase, p38 kinase, and PKC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|