Effects of Sulfonylureas on Peroxisome Proliferator-Activated Receptor gamma Activity and on Glucose Uptake by Thiazolidinediones

BACKGROUND: Sulfonylurea primarily stimulates insulin secretion by binding to its receptor on the pancreatic beta-cells. Recent studies have suggested that sulfonylureas induce insulin sensitivity through peroxisome proliferator-activated receptor gamma (PPARgamma), one of the nuclear receptors. In this study, we investigated the effects of sulfonylurea on PPARgamma transcriptional activity and on the glucose uptake via PPARgamma. METHODS: Transcription reporter assays using Cos7 cells were performed to determine if specific sulfonylureas stimulate PPARgamma transactivation. Glimepiride, gliquidone, and glipizide (1 to 500 microM) were used as treatment, and rosiglitazone at 1 and 10 microM was used as a control. The effects of sulfonylurea and rosiglitazone treatments on the transcriptional activity of endogenous PPARgamma were observed. In addition, 3T3-L1 adipocytes were treated with rosiglitazone (10 microM), glimepiride (100 microM) or both to verify the effect of glimepiride on rosiglitazone-induced glucose uptake. RESULTS: Sulfonylureas, including glimepiride, gliquidone and glipizide, increased PPARgamma transcriptional activity, gliquidone being the most potent PPARgamma agonist. However, no additive effects were observed in the presence of rosiglitazone. When rosiglitazone was co-treated with glimepiride, PPARgamma transcriptional activity and glucose uptake were reduced compared to those after treatment with rosiglitazone alone. This competitive effect of glimepiride was observed only at high concentrations that are not achieved with clinical doses. CONCLUSION: Sulfonylureas like glimepiride, gliquidone and glipizide increased the transcriptional activity of PPARgamma. Also, glimepiride was able to reduce the effect of rosiglitazone on PPARgamma agonistic activity and glucose uptake. However, the competitive effect does not seem to occur at clinically feasible concentrations.

Silica Induced Apoptosis In Vitro and In Vivo / 대한산업의학회지

Silica exposure results in acute inflammatory response followed by chronic fibrotic change. The mechanism for the maintenance of silica-induced inflammation has not been understood yet. Apoptosis is a morphologically distinct form of programed cell death that plays major role during homeostasis and in many diseases including cancer, acquired immune deficiency syndrome and neurodegenerative disorders. Apoptosis is characterized by cell shrinkage, membrane blebbing and nuclear condensation. To demonstrate the involvement of apoptosis in underlying mechanism for the development of silica-induced pathological changes, this study was designed in vitro and in vivo models. In in vitro study, alveolar epithelial cell line (A549) was stimulated with silica and performed flow cytometry and DNA electrophoresis. In in vivo study, bronchoalveolar lavage (BAL) was done to count the total and apoptotic cells from silica-instilled rats. The results were as follows: 1. Apoptotic cell fraction of silica-treated groups (10 and 50 microgram/cm2) was significantly higher than that of control group. 2. Genomic DNA from silica-treated groups (10 and 50 microgram/cm2 ) showed DNA ladder in agarose gel electrophoresis, while group of 1 microgram/cm2 didn't. 3. Total cell number and apoptotic cell number of BAL fluid from silica-instilled rats (10, 20 and 40 mg/kg) were significantly higher than those of control. 4. Silica induced apoptosis of cells in BAL fluid was confirmed by microscopic observation with nuclear fragmentation. These results suggest that apoptosis may contribute to development of silica-induced pathological changes.

The Changes of Knowledge, Attitude and Practice about Health Promotion in Workers Taking Group Occupational Health Service for 5 years / 대한산업의학회지

Before and after conducting the health promotion program by group occupational health service during 5 years, we surveyed knowledge, attitude and practice about general health(30 items) and occupational health (30 items) among 25 small and medium scale industry workers (before : 355 workers, after : 279 workers) for evaluation of effectiveness. The scores of knowledge for smoking, drinking, cholesterol, mental stress, management of hypertension, and risks in younger or women workers were significantly increased after conducting group occupational health service. The scorers of attitude for controlling of fatty food consumption and cleaning workplace and bathing for health and that of practice for taking the periodic health examination and choking blood pressure were significantly increased but most of items in attitude and practice didn't be changed after services. According to sex, the scorers of men were significantly increased in knowledge of general health, but there were not significant differences in age, job status and work duration group. In conclusion, through the group occupational health service during 5 years, only the scores of knowledge in general health were increased. It suggested that the effective program which can change workers' attitude and practice for health promotion, should be developed and conducted in small and medium scale industry workers.