PMID- 31669915
OWN - NLM
STAT- MEDLINE
DCOM- 20200331
LR  - 20200331
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 120
DP  - 2019 Dec
TI  - Glucagon-like peptide-1 receptor expression and its functions are regulated by 
      androgen.
PG  - 109555
LID - S0753-3322(19)33465-1 [pii]
LID - 10.1016/j.biopha.2019.109555 [doi]
AB  - Glucagon-like peptide-1 receptor (GLP-1R) is an important pharmacological target 
      for type 2 diabetes mellitus because it maintains glucose homeostasis and 
      promotes beta cell proliferation. Androgen is suggested not only to regulate 
      hypothalamic-pituitary-gonadal axis but also to affect metabolism. In this study, 
      Glp1r mRNA was found widely expressed in normal male mice and its levels were 
      positively correlated with the serum testosterone (T) concentrations. Using mouse 
      insulinoma 6 (MIN6) cells, which highly express GLP-1R, we observed GLP-1R was 
      upregulated both at transcriptional and protein levels induced by 
      dihydrotestosterone (DHT) and was downregulated by androgen receptor inhibitor 
      ARN-509 or small interfering RNA (siRNA) targeting Glp1r mRNA. In normal C57BL/6 
      mice and db/db mice, Glp1r mRNA levels in the pancreases increased in the DHT 
      treatment group and decreased in the ARN-509 treatment group. And the increased 
      GLP-1R expression had insulinotropic function both in vitro and in vivo. Further 
      analysis showed that the androgen receptor (Ar) located in the cytosol of MIN6 
      cells and translocated to the nucleus after DHT treatment. In addition, we found 
      that there was an Ar motif in the promoter region of the Glp1r gene. Further 
      studies revealed that the translocated DHT/Ar complex from the cytosol to the 
      nucleus bound to the Ar motif of the Glp1r gene and upregulated gene 
      transcription. Taken together, the widely expressed GLP-1R was positively 
      regulated by androgen under physiological condition and in diabetic models at the 
      transcriptional level.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Masson SAS.. All rights 
      reserved.
FAU - Zhu, Liying
AU  - Zhu L
AD  - Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University 
      School of Medicine, No. 197, Ruijin 2nd Road, Shanghai 200025, China. Electronic 
      address: tianshi_baba@163.com.
FAU - Zhou, Jinxing
AU  - Zhou J
AD  - Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University 
      School of Medicine, No. 197, Ruijin 2nd Road, Shanghai 200025, China. Electronic 
      address: happyzhoujx@126.com.
FAU - Pan, Yu
AU  - Pan Y
AD  - Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University 
      School of Medicine, No. 197, Ruijin 2nd Road, Shanghai 200025, China. Electronic 
      address: dimi_luki@163.com.
FAU - Lv, Jing
AU  - Lv J
AD  - Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University 
      School of Medicine, No. 197, Ruijin 2nd Road, Shanghai 200025, China. Electronic 
      address: ljmighty@163.com.
FAU - Liu, Yang
AU  - Liu Y
AD  - Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University 
      School of Medicine, No. 197, Ruijin 2nd Road, Shanghai 200025, China. Electronic 
      address: liuyang_950922@163.com.
FAU - Yu, Shanhe
AU  - Yu S
AD  - State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology and 
      Collaborative Innovation Center of Hematology, Ruijin Hospital, Shanghai Jiao 
      Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai 200025, 
      China. Electronic address: yushanhe5460@163.com.
FAU - Zhang, Yifan
AU  - Zhang Y
AD  - Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University 
      School of Medicine, No. 197, Ruijin 2nd Road, Shanghai 200025, China. Electronic 
      address: zhang_yifan@126.com.
LA  - eng
PT  - Journal Article
DEP - 20191024
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (Androgens)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Receptors, Androgen)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 3XMK78S47O (Testosterone)
SB  - IM
MH  - Androgens/*pharmacology
MH  - Animals
MH  - Cell Line
MH  - Cell Membrane/metabolism
MH  - Cell Nucleus/drug effects/metabolism
MH  - Cell Proliferation/drug effects
MH  - Dihydrotestosterone/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Glucagon-Like Peptide-1 Receptor/genetics/*metabolism
MH  - Insulin Secretion/drug effects
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Models, Biological
MH  - Organ Specificity
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Transport/drug effects
MH  - Receptors, Androgen/metabolism
MH  - Sexual Maturation
MH  - Testosterone/blood
MH  - Transcription, Genetic/drug effects
OTO - NOTNLM
OT  - DHT/Ar
OT  - GLP-1R
OT  - Insulin
OT  - Type 2 diabetes mellitus
EDAT- 2019/11/02 06:00
MHDA- 2020/04/01 06:00
CRDT- 2019/11/01 06:00
PHST- 2019/07/18 00:00 [received]
PHST- 2019/10/11 00:00 [revised]
PHST- 2019/10/11 00:00 [accepted]
PHST- 2019/11/02 06:00 [pubmed]
PHST- 2020/04/01 06:00 [medline]
PHST- 2019/11/01 06:00 [entrez]
AID - S0753-3322(19)33465-1 [pii]
AID - 10.1016/j.biopha.2019.109555 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2019 Dec;120:109555. doi: 10.1016/j.biopha.2019.109555. Epub 
      2019 Oct 24.