FXR Mediates Adenylyl Cyclase 8 Expression in Pancreatic β-Cells
Adenylyl cyclase 8 (ADCY8) and Farnesoid X Receptor (FXR) have been identified in pancreatic β-cells and play important roles in insulin secretion. But the mechanisms underlying with respect to the regulation of ADCY8 expression in β-cells, particularly whether FXR is involved, remain unexplored. We...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2019/8915818 |
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| author | Xiangchen Kong Bingfeng Li Yushen Deng Xiaosong Ma |
| author_facet | Xiangchen Kong Bingfeng Li Yushen Deng Xiaosong Ma |
| author_sort | Xiangchen Kong |
| collection | DOAJ |
| description | Adenylyl cyclase 8 (ADCY8) and Farnesoid X Receptor (FXR) have been identified in pancreatic β-cells and play important roles in insulin secretion. But the mechanisms underlying with respect to the regulation of ADCY8 expression in β-cells, particularly whether FXR is involved, remain unexplored. We now show that ADCY8 expression is decreased in Goto-Kakizaki (GK) rat islets compared with healthy Wistar controls. We also found that reduced ADCY8 is associated with decreased expression of FXR. Consistently, ADCY8 expression was suppressed by the knockdown of FXR in INS-1 832/13 cells, as well as the islets from FXR knockout mice. On the contrary, ADCY8 expression was increased in FXR-overexpressed INS-1 832/13 cells or in the case of FXR activation. Mechanistically, FXR directly binds to Adcy8 promoter and recruits the histone acetyltransferase Steroid Receptor Coactivator 1 (SRC1), thereby resulting in the increased acetylation of histone H3 in Adcy8 locus, promoting Adcy8 gene transcription in β-cells. Thus, this study indicates that FXR is a critical transcription factor that mediates ADCY8 expression in pancreatic β-cells and has characterized the chromatin modification associated with Adcy8 transcription. |
| format | Article |
| id | doaj-art-d33489ddb6f740ca92be5273b8179a8b |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-d33489ddb6f740ca92be5273b8179a8b2025-02-03T05:51:54ZengWileyJournal of Diabetes Research2314-67452314-67532019-01-01201910.1155/2019/89158188915818FXR Mediates Adenylyl Cyclase 8 Expression in Pancreatic β-CellsXiangchen Kong0Bingfeng Li1Yushen Deng2Xiaosong Ma3Shenzhen University Diabetes Institute, School of Medicine, Shenzhen University, Shenzhen 518060, ChinaShenzhen University Diabetes Institute, School of Medicine, Shenzhen University, Shenzhen 518060, ChinaCollege of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, ChinaShenzhen University Diabetes Institute, School of Medicine, Shenzhen University, Shenzhen 518060, ChinaAdenylyl cyclase 8 (ADCY8) and Farnesoid X Receptor (FXR) have been identified in pancreatic β-cells and play important roles in insulin secretion. But the mechanisms underlying with respect to the regulation of ADCY8 expression in β-cells, particularly whether FXR is involved, remain unexplored. We now show that ADCY8 expression is decreased in Goto-Kakizaki (GK) rat islets compared with healthy Wistar controls. We also found that reduced ADCY8 is associated with decreased expression of FXR. Consistently, ADCY8 expression was suppressed by the knockdown of FXR in INS-1 832/13 cells, as well as the islets from FXR knockout mice. On the contrary, ADCY8 expression was increased in FXR-overexpressed INS-1 832/13 cells or in the case of FXR activation. Mechanistically, FXR directly binds to Adcy8 promoter and recruits the histone acetyltransferase Steroid Receptor Coactivator 1 (SRC1), thereby resulting in the increased acetylation of histone H3 in Adcy8 locus, promoting Adcy8 gene transcription in β-cells. Thus, this study indicates that FXR is a critical transcription factor that mediates ADCY8 expression in pancreatic β-cells and has characterized the chromatin modification associated with Adcy8 transcription.http://dx.doi.org/10.1155/2019/8915818 |
| spellingShingle | Xiangchen Kong Bingfeng Li Yushen Deng Xiaosong Ma FXR Mediates Adenylyl Cyclase 8 Expression in Pancreatic β-Cells Journal of Diabetes Research |
| title | FXR Mediates Adenylyl Cyclase 8 Expression in Pancreatic β-Cells |
| title_full | FXR Mediates Adenylyl Cyclase 8 Expression in Pancreatic β-Cells |
| title_fullStr | FXR Mediates Adenylyl Cyclase 8 Expression in Pancreatic β-Cells |
| title_full_unstemmed | FXR Mediates Adenylyl Cyclase 8 Expression in Pancreatic β-Cells |
| title_short | FXR Mediates Adenylyl Cyclase 8 Expression in Pancreatic β-Cells |
| title_sort | fxr mediates adenylyl cyclase 8 expression in pancreatic β cells |
| url | http://dx.doi.org/10.1155/2019/8915818 |
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