PMID- 33611845
OWN - NLM
STAT- MEDLINE
DCOM- 20240318
LR  - 20240318
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 28
IP  - 6
DP  - 2024 Mar
TI  - FXR-mediated epigenetic regulation of GLP-1R expression contributes to enhanced 
      incretin effect in diabetes after RYGB.
PG  - e16339
LID - 10.1111/jcmm.16339 [doi]
LID - e16339
AB  - 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 
      beta-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 
      beta-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 beta-cells, which results in enhanced incretin effect and 
      normalized blood glucose of GK rats after RYGB.
CI  - (c) 2021 The Authors. Journal of Cellular and Molecular Medicine published by 
      Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
FAU - Kong, Xiangchen
AU  - Kong X
AUID- ORCID: 0000-0001-5149-1987
AD  - Shenzhen University Diabetes Institute, School of Medicine, Shenzhen University, 
      Shenzhen, China.
FAU - Feng, Linxian
AU  - Feng L
AD  - Shenzhen University Diabetes Institute, School of Medicine, Shenzhen University, 
      Shenzhen, China.
FAU - Yan, Dan
AU  - Yan D
AD  - Shenzhen University Diabetes Institute, School of Medicine, Shenzhen University, 
      Shenzhen, China.
FAU - Li, Bingfeng
AU  - Li B
AD  - Shenzhen University Diabetes Institute, School of Medicine, Shenzhen University, 
      Shenzhen, China.
FAU - Yang, Yanhui
AU  - Yang Y
AD  - Shenzhen University Diabetes Institute, School of Medicine, Shenzhen University, 
      Shenzhen, China.
FAU - Ma, Xiaosong
AU  - Ma X
AD  - Shenzhen University Diabetes Institute, School of Medicine, Shenzhen University, 
      Shenzhen, China.
LA  - eng
GR  - A2020530/Medical Scientific Research Foundation of Guangdong Province of China/
GR  - 81370914, 81670708, 82070845, 82070806, 81400801/National Natural Science 
      Foundation of China/
GR  - ZDSYS20190902092903237/Shenzhen Key Laboratory of Metabolism and Cardiovascular 
      Homeostasis/
PT  - Journal Article
DEP - 20210221
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Blood Glucose)
RN  - 0 (Glp1r protein, rat)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 0 (Incretins)
RN  - 0 (Insulin)
RN  - 0C5V0MRU6P (farnesoid X-activated receptor)
SB  - IM
MH  - Animals
MH  - Rats
MH  - Blood Glucose/metabolism
MH  - *Diabetes Mellitus, Type 2/genetics/surgery
MH  - Epigenesis, Genetic
MH  - *Gastric Bypass
MH  - Glucagon-Like Peptide 1/genetics/metabolism
MH  - Incretins/metabolism
MH  - Insulin/metabolism
PMC - PMC10941525
OTO - NOTNLM
OT  - FXR
OT  - GLP-1 receptor
OT  - RYGB
OT  - diabetes
OT  - epigenetic regulation
COIS- The authors confirm that there are no conflicts of interest.
EDAT- 2021/02/22 06:00
MHDA- 2024/03/18 06:42
PMCR- 2021/02/21
CRDT- 2021/02/21 20:45
PHST- 2021/01/02 00:00 [revised]
PHST- 2020/10/05 00:00 [received]
PHST- 2021/01/06 00:00 [accepted]
PHST- 2024/03/18 06:42 [medline]
PHST- 2021/02/22 06:00 [pubmed]
PHST- 2021/02/21 20:45 [entrez]
PHST- 2021/02/21 00:00 [pmc-release]
AID - JCMM16339 [pii]
AID - 10.1111/jcmm.16339 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2024 Mar;28(6):e16339. doi: 10.1111/jcmm.16339. Epub 2021 Feb 21.