FXR-mediated epigenetic regulation of GLP-1R expression contributes to enhanced incretin effect in diabetes after RYGB
© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd..
In this study, we investigated how Roux-en-Y gastric bypass (RYGB) enhances glucagon-like peptide 1 (GLP-1) response in GK rats and explored the potential link between RYGB-stimulated BAs/FXR signalling and GLP-1R-linked signalling in β-cells, a key pathway that regulates glucose-stimulated insulin secretion (GSIS). Here we show that RYGB restores GLP-1R expression in GK rat islets. This involves increased total BAs as well as chenodeoxycholic acid (CDCA), leading to FXR activation, increasing FXR binding to the promoter of Glp-1r and enhancing occupancy of histone acetyltransferase steroid receptor coactivator-1 (SRC1), thus increasing histone H3 acetylation at the promoter. These coordinated events bring about increased GLP-1R expression, resulting in greater GLP-1 response in β-cells. Moreover, ablation of FXR suppressed the stimulatory effects of GLP-1. Thus, this study unravels the crucial role of the BAs/FXR/SRC1 axis-controlled GLP-1R expression in β-cells, which results in enhanced incretin effect and normalized blood glucose of GK rats after RYGB.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
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| Enthalten in: |
Journal of cellular and molecular medicine - 28(2024), 6 vom: 31. März, Seite e16339 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kong, Xiangchen [VerfasserIn] |
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| Links: |
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| Themen: |
0C5V0MRU6P |
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| Anmerkungen: |
Date Completed 18.03.2024 Date Revised 18.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/jcmm.16339 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM321704401 |
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| 520 | |a © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. | ||
| 520 | |a In this study, we investigated how Roux-en-Y gastric bypass (RYGB) enhances glucagon-like peptide 1 (GLP-1) response in GK rats and explored the potential link between RYGB-stimulated BAs/FXR signalling and GLP-1R-linked signalling in β-cells, a key pathway that regulates glucose-stimulated insulin secretion (GSIS). Here we show that RYGB restores GLP-1R expression in GK rat islets. This involves increased total BAs as well as chenodeoxycholic acid (CDCA), leading to FXR activation, increasing FXR binding to the promoter of Glp-1r and enhancing occupancy of histone acetyltransferase steroid receptor coactivator-1 (SRC1), thus increasing histone H3 acetylation at the promoter. These coordinated events bring about increased GLP-1R expression, resulting in greater GLP-1 response in β-cells. Moreover, ablation of FXR suppressed the stimulatory effects of GLP-1. Thus, this study unravels the crucial role of the BAs/FXR/SRC1 axis-controlled GLP-1R expression in β-cells, which results in enhanced incretin effect and normalized blood glucose of GK rats after RYGB | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Li, Bingfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yanhui |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Xiaosong |e verfasserin |4 aut | |
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