title: Dexamethasone rapidly inhibits glucose uptake via non-genomic mechanisms in contracting myotubes.
abstract: Glucocorticoids (GCs) are a class of steroid hormones that regulate multiple aspects of glucose homeostasis. In skeletal muscle, it is well established that prolonged GC excess inhibits glucose uptake and utilization through glucocorticoid receptor (GR)-mediated transcriptional changes. However, it remains obscure that whether the rapid non-genomic effects of GC on glucose uptake are involved in acute exercise stress. Therefore, we used electric pulse stimulation (EPS)-evoked contracting myotubes to determine whether the non-genomic actions of GC were involved and its underlying mechanism(s). Pretreatment with dexamethasone (Dex, 10 μM) significantly prevented contraction-stimulated glucose uptake and glucose transporter 4 (Glut4) translocation within 20 min in C2C12 myotubes. Neither GC nuclear receptor antagonist (RU486) nor protein synthesis inhibitor (cycloheximide, Chx) affected the rapid inhibition effects of Dex. AMPK and CaMKII-dependent signaling pathways were associated with the non-genomic effects of Dex. These results provide evidence that GC rapidly suppresses glucose uptake in contracting myotubes via GR-independent non-genomic mechanisms. AMPK and CaMKII-mediated Glut4 translocation may play a critical role in GC-induced rapid inhibition of glucose uptake.
authors.affiliation: Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Gong
authors.affiliation: Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, People's Republics of China.
authors.forename: Chen-Xu
authors.initials: CX
authors.lastname: Ni
authors.affiliation: Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Su
authors.affiliation: Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Lian
authors.affiliation: Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.affiliation: Department of Pharmacy, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Zhang
authors.affiliation: Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, People's Republic of China. Electronic address: cljiang@vip.163.com.
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Jiang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003513:Cycloheximide / Q000737:chemistry; D003907:Dexamethasone / Q000737:chemistry*; D023281:Genomics; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D051379:Mice; D015735:Mifepristone / Q000737:chemistry; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D021381:Protein Transport; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D015398:Signal Transduction; D013256:Steroids / Q000737:chemistry; D014158:Transcription, Genetic
chemical_list: D000893:Anti-Inflammatory Agents; D051275:Glucose Transporter Type 4; D011965:Receptors, Glucocorticoid; C495693:Slc2a4 protein, mouse; D013256:Steroids; D015735:Mifepristone; D003907:Dexamethasone; D000255:Adenosine Triphosphate; D003513:Cycloheximide; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D005947:Glucose; D002118:Calcium
keywords: C2C12 myotube; Contraction; Glucocorticoid; Glucose uptake; Glut4 translocation; Non-genomic effect