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. 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. 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. SIGNIFICANCE: These results demonstrate that clozapine increases glucose uptake through CaMKK-AMPK pathway in myotube C2C12 cells.
Subject(s)
AMP-Activated Protein Kinases/drug effects , Antipsychotic Agents/pharmacology , Clozapine/pharmacology , Glucose/metabolism , Muscle Fibers, Skeletal/metabolism , 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 CountingABSTRACT
The prevalence of neurodegenerative disorders is not well documented in Korea. We assessed the prevalence of Parkinson's disease in an elderly population in a newly industrialized city in a rural region. Subjects for this study were randomly selected from a community-based cohort study. The sample in the cohort represented approximately 1.3% (4700) of 362 625 adults (age>18 years) listed in the city register in 1998. Among this group, 4218 subjects (1086 subjects aged>60 years) agreed to be interviewed and underwent a physical examination and neuropsychological tests administered by a neurologist and neuropsychologist. All participants were examined. Participants who had bradykinesia and at least one other possible cardinal sign of parkinsonism at the neurologic screening, and those who reported that they had Parkinson's disease, or were taking antiparkinsonian drugs were identified. In our study, 16 subjects showed evidence of Parkinson's disease. The prevalence in this population was 0.37%. Prevalence increased with age, and prevalence was 1.47% for those aged older than 60 years. Postural instability and gait disturbance were more common in the older age group. The results of neuropsychological tests were as follows: (1) only two subjects had low scores (<20) in the Korea-version mini-mental status examination; (2) seven subjects scored 0.5, one subject scored 2 and the other eight subjects scored 0 in the clinical dementia rating. The results of our prevalence study are similar to those of studies carried out in Western countries. Age is a risk factor for Parkinson's disease in Korea.
