ABSTRACT
Obesity is consistently increasing in prevalence and can trigger insulin resistance and type 2 diabetes. Many lines of evidence have shown that macrophages play a major role in inflammation associated with obesity. This study was conducted to determine metformin, a widely prescribed drug for type 2 diabetes, would regulate inflammation through down-regulation of scavenger receptors in macrophages from obesity-induced type 2 diabetes. RAW 264.7 cells and peritoneal macrophages were stimulated with LPS to induce inflammation, and C57BL/6N mice were fed a high-fat diet to generate obesity-induced type 2 diabetes mice. Metformin reduced the production of NO, PGE2 and pro-inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) through down-regulation of NF-kappaB translocation in macrophages in a dose-dependent manner. On the other hand, the protein expressions of anti-inflammatory cytokines, IL-4 and IL-10, were enhanced or maintained by metformin. Also, metformin suppressed secretion of TNF-alpha and reduced the protein and mRNA expression of TNF-alpha in obese mice as well as in macrophages. The expression of scavenger receptors, CD36 and SR-A, were attenuated by metformin in macrophages and obese mice. These results suggest that metformin may attenuate inflammatory responses by suppressing the production of TNF-alpha and the expressions of scavenger receptors.
Subject(s)
Animals , Mice , Cytokines , Diet, High-Fat , Dinoprostone , Down-Regulation , Hand , Inflammation , Insulin Resistance , Interleukin-10 , Interleukin-4 , Interleukin-6 , Macrophages , Macrophages, Peritoneal , Metformin , Mice, Obese , NF-kappa B , Obesity , Prevalence , Receptors, Scavenger , RNA, Messenger , Tumor Necrosis Factor-alphaABSTRACT
OBJECTIVE: Elderly Dementia and depression are major neuropsychiatric disorders. Epidemiologic study considered essential part to evaluate and treatment guideline for community mental health. METHOD: The cross-sectional study evaluates the dementia and depression of community- living elderly, over 65 older in a Korean rural community. Mini-Mental State Examination- Korean (MMSE-K) and Geriatric Depression Scale (GDS) was conducted. RESULTS: The prevalence of dementia is 14.0% below the 17 of MMSE-K score. Cognitive function decline is increasing with age. The prevalence of dementia in female elderly is higher than that in male with statistical significance (p<.001). The prevalence of depression is 10% among elderly population. Female elderly have higher frequency than male with statistical significance. CONCLUSION: Elderly dementia and depression is very important neuropsychiatric disorders. MMSE-K and GDS-K is useful instruments for evaluation of elderly dementia and depression. Age and sex are important factors for dementia and depression. More developed instruments for accurate detection and differentiation of dementia and depression are need for mental health program to manage effectively them.
Subject(s)
Aged , Female , Humans , Male , Cross-Sectional Studies , Dementia , Depression , Epidemiologic Studies , Epidemiology , Mental Health , Prevalence , Rural PopulationABSTRACT
In excitable and endocrine organs, calcium influxes through the voltage-dependent calcium channel (VDCC), composed of four (alpha 1, alpha 2, beta, and gamma) subunits. Four isoforms of beta subunits (beta 1, beta 2, beta 3, beta 4) are known to exist, The cytoplasmic beta subunits regulate the channel activity by accelerating the kinetics of activation and inactivation through phosphorylation. Regulation of calcium channel activities are also provided by alternative splicing of the beta subunits. To elucidate the genomic organization of the VDCC beta 3 subunit gene, two genomic clones were isolated from human genomic liabrary using the whole rat cDNA for beta 3 subunit as a probe. The beta 3 subunit gene in lamda phage DNA was analyzed by Southern hybridization and sequencing. A 19.1 kb clone (2BHG13) contained the whole beta 3 cDNA sequence, consisting at least 14 exons. The deduced amino acid sequence from the exons shows 97% similarity with that of rat gene. Two alternatively spliced forms of beta 3 subunit at 5'-end were found. The beta 3 subunit had many possible phosphorylation sites. Alternative splicing of beta 3 subunit mRNA at 5'-end and phosphorylation of the beta 3 subunit protein may play a regulatory role in calcium influxes.