Effects of Sulfonylureas on Peroxisome Proliferator-Activated Receptor γ Activity and on Glucose Uptake by Thiazolidinediones
BackgroundSulfonylurea primarily stimulates insulin secretion by binding to its receptor on the pancreatic β-cells. Recent studies have suggested that sulfonylureas induce insulin sensitivity through peroxisome proliferator-activated receptor γ (PPARγ), one of the nuclear receptors. In this study, w...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Korean Diabetes Association
2011-08-01
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| Series: | Diabetes & Metabolism Journal |
| Subjects: | |
| Online Access: | http://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-35-340.pdf |
| _version_ | 1818683627492343808 |
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| author | Kyeong Won Lee Yun Hyi Ku Min Kim Byung Yong Ahn Sung Soo Chung Kyong Soo Park |
| author_facet | Kyeong Won Lee Yun Hyi Ku Min Kim Byung Yong Ahn Sung Soo Chung Kyong Soo Park |
| author_sort | Kyeong Won Lee |
| collection | DOAJ |
| description | BackgroundSulfonylurea primarily stimulates insulin secretion by binding to its receptor on the pancreatic β-cells. Recent studies have suggested that sulfonylureas induce insulin sensitivity through peroxisome proliferator-activated receptor γ (PPARγ), one of the nuclear receptors. In this study, we investigated the effects of sulfonylurea on PPARγ transcriptional activity and on the glucose uptake via PPARγ.MethodsTranscription reporter assays using Cos7 cells were performed to determine if specific sulfonylureas stimulate PPARγ transactivation. Glimepiride, gliquidone, and glipizide (1 to 500 µM) were used as treatment, and rosiglitazone at 1 and 10 µM was used as a control. The effects of sulfonylurea and rosiglitazone treatments on the transcriptional activity of endogenous PPARγ were observed. In addition, 3T3-L1 adipocytes were treated with rosiglitazone (10 µM), glimepiride (100 µM) or both to verify the effect of glimepiride on rosiglitazone-induced glucose uptake.ResultsSulfonylureas, including glimepiride, gliquidone and glipizide, increased PPARγ transcriptional activity, gliquidone being the most potent PPARγ agonist. However, no additive effects were observed in the presence of rosiglitazone. When rosiglitazone was co-treated with glimepiride, PPARγ 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.ConclusionSulfonylureas like glimepiride, gliquidone and glipizide increased the transcriptional activity of PPARγ. Also, glimepiride was able to reduce the effect of rosiglitazone on PPARγ agonistic activity and glucose uptake. However, the competitive effect does not seem to occur at clinically feasible concentrations. |
| first_indexed | 2024-12-17T10:37:45Z |
| format | Article |
| id | doaj.art-57f65d2de31a49059448650e1add4849 |
| institution | Directory Open Access Journal |
| issn | 2233-6079 2233-6087 |
| language | English |
| last_indexed | 2024-12-17T10:37:45Z |
| publishDate | 2011-08-01 |
| publisher | Korean Diabetes Association |
| record_format | Article |
| series | Diabetes & Metabolism Journal |
| spelling | doaj.art-57f65d2de31a49059448650e1add48492022-12-21T21:52:19ZengKorean Diabetes AssociationDiabetes & Metabolism Journal2233-60792233-60872011-08-0135434034710.4093/dmj.2011.35.4.3402649Effects of Sulfonylureas on Peroxisome Proliferator-Activated Receptor γ Activity and on Glucose Uptake by ThiazolidinedionesKyeong Won LeeYun Hyi KuMin KimByung Yong AhnSung Soo ChungKyong Soo ParkBackgroundSulfonylurea primarily stimulates insulin secretion by binding to its receptor on the pancreatic β-cells. Recent studies have suggested that sulfonylureas induce insulin sensitivity through peroxisome proliferator-activated receptor γ (PPARγ), one of the nuclear receptors. In this study, we investigated the effects of sulfonylurea on PPARγ transcriptional activity and on the glucose uptake via PPARγ.MethodsTranscription reporter assays using Cos7 cells were performed to determine if specific sulfonylureas stimulate PPARγ transactivation. Glimepiride, gliquidone, and glipizide (1 to 500 µM) were used as treatment, and rosiglitazone at 1 and 10 µM was used as a control. The effects of sulfonylurea and rosiglitazone treatments on the transcriptional activity of endogenous PPARγ were observed. In addition, 3T3-L1 adipocytes were treated with rosiglitazone (10 µM), glimepiride (100 µM) or both to verify the effect of glimepiride on rosiglitazone-induced glucose uptake.ResultsSulfonylureas, including glimepiride, gliquidone and glipizide, increased PPARγ transcriptional activity, gliquidone being the most potent PPARγ agonist. However, no additive effects were observed in the presence of rosiglitazone. When rosiglitazone was co-treated with glimepiride, PPARγ 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.ConclusionSulfonylureas like glimepiride, gliquidone and glipizide increased the transcriptional activity of PPARγ. Also, glimepiride was able to reduce the effect of rosiglitazone on PPARγ agonistic activity and glucose uptake. However, the competitive effect does not seem to occur at clinically feasible concentrations.http://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-35-340.pdfDiabetes mellitus, type 2Peroxisome proliferator-activated receptorsPPAR gammaSulfonylurea compoundsThiazolidinediones |
| spellingShingle | Kyeong Won Lee Yun Hyi Ku Min Kim Byung Yong Ahn Sung Soo Chung Kyong Soo Park Effects of Sulfonylureas on Peroxisome Proliferator-Activated Receptor γ Activity and on Glucose Uptake by Thiazolidinediones Diabetes & Metabolism Journal Diabetes mellitus, type 2 Peroxisome proliferator-activated receptors PPAR gamma Sulfonylurea compounds Thiazolidinediones |
| title | Effects of Sulfonylureas on Peroxisome Proliferator-Activated Receptor γ Activity and on Glucose Uptake by Thiazolidinediones |
| title_full | Effects of Sulfonylureas on Peroxisome Proliferator-Activated Receptor γ Activity and on Glucose Uptake by Thiazolidinediones |
| title_fullStr | Effects of Sulfonylureas on Peroxisome Proliferator-Activated Receptor γ Activity and on Glucose Uptake by Thiazolidinediones |
| title_full_unstemmed | Effects of Sulfonylureas on Peroxisome Proliferator-Activated Receptor γ Activity and on Glucose Uptake by Thiazolidinediones |
| title_short | Effects of Sulfonylureas on Peroxisome Proliferator-Activated Receptor γ Activity and on Glucose Uptake by Thiazolidinediones |
| title_sort | effects of sulfonylureas on peroxisome proliferator activated receptor γ activity and on glucose uptake by thiazolidinediones |
| topic | Diabetes mellitus, type 2 Peroxisome proliferator-activated receptors PPAR gamma Sulfonylurea compounds Thiazolidinediones |
| url | http://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-35-340.pdf |
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