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Clozapine activates AMP-activated protein kinase (AMPK) in C2C12 myotube cells and stimulates glucose uptake.
- Source :
-
Life sciences [Life Sci] 2010 Jul 03; Vol. 87 (1-2), pp. 42-8. Date of Electronic Publication: 2010 May 31. - Publication Year :
- 2010
-
Abstract
- Aims: Clozapine has previously been implicated in the dysregulation of energy balance and glucose metabolism in the central nervous system, but its effects in the periphery have yet to be thoroughly elucidated. The objective of this study was to characterize the effects of clozapine on AMP-activated protein kinase (AMPK) activity in the skeletal muscles.<br />Main Methods: Myotube C2C12 cells were incubated under control conditions, or with clozapine. Expression levels of phosphorylation status of AMPK and its direct downstream Acetyl-CoA carboxylase (ACC) were analyzed by Western blot. Intracellular calcium concentration was measured with calcium indicator dye, fluo-3AM. 2-deoxyglucose uptake was assessed via the scintillation count.<br />Key Findings: We reported that clozapine activated AMPK in mouse C2C12 myotubes and also stimulated glucose uptake. Clozapine also increased intracellular calcium concentrations of C2C12 cells, and pretreatment with either ethylenediaminetetraacetic acid (EDTA), an extracellular calcium chelator, or 1.8-naphthoylene benzimidazole-3-carboxylic acid (STO-609), a Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK) inhibitor, blocked clozapine-induced AMPK activation.<br />Significance: These results demonstrate that clozapine increases glucose uptake through CaMKK-AMPK pathway in myotube C2C12 cells.<br /> (Copyright (c) 2010 Elsevier Inc. All rights reserved.)
- Subjects :
- AMP-Activated Protein Kinases metabolism
Acetyl-CoA Carboxylase drug effects
Acetyl-CoA Carboxylase metabolism
Animals
Blotting, Western
Calcium metabolism
Calcium-Calmodulin-Dependent Protein Kinase Kinase drug effects
Calcium-Calmodulin-Dependent Protein Kinase Kinase metabolism
Cell Line
Mice
Muscle Fibers, Skeletal cytology
Muscle Fibers, Skeletal drug effects
Phosphorylation drug effects
Scintillation Counting
AMP-Activated Protein Kinases drug effects
Antipsychotic Agents pharmacology
Clozapine pharmacology
Glucose metabolism
Muscle Fibers, Skeletal metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0631
- Volume :
- 87
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 20515698
- Full Text :
- https://doi.org/10.1016/j.lfs.2010.05.017