PMID- 29118086
OWN - NLM
STAT- MEDLINE
DCOM- 20181106
LR  - 20220409
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 32
IP  - 3
DP  - 2018 Mar
TI  - CREB/CRTC2 controls GLP-1-dependent regulation of glucose homeostasis.
PG  - 1566-1578
LID - 10.1096/fj.201700845R [doi]
AB  - Glucagon-like peptide 1 (GLP-1) is a major incretin that controls glucose 
      homeostasis. The secretion of mature GLP-1 is regulated via GPCRs, including bile 
      acid receptor G protein-coupled bile acid receptor 1, which uses cAMP signaling 
      to enhance the exocytosis of GLP-1-containing vesicles. However, the role of 
      cAMP-mediated transcription has not been clearly demonstrated to date. In this 
      study, we explored the role of cAMP response element-binding 
      protein/CREB-regulated transcription coactivator 2 (CREB/CRTC2)-dependent 
      transcription on GLP-1 secretion in the L cells. We found that the reduced 
      CREB/CRTC2 activity impaired the cAMP-dependent increase in GLP-1 secretion, 
      whereas expression of constitutively active CRTC2 increased GLP-1 exocytosis from 
      the L cells. Close investigation revealed that expression of not only proglucagon 
      but also PC1/3, an endopeptidase for GLP-1 maturation, is transcriptionally 
      regulated by CREB/CRTC2. Furthermore, expression of peroxisome 
      proliferator-activating receptor coactivator 1 alpha is also reduced upon depletion 
      of CRTC2, leading to the decreased expression of oxidative phosphorylation 
      (OxPhos) genes, reduced ATP levels, and calcium concentrations in the L cells. 
      Finally, we observed that intestine-specific CRTC2 knockout mice displayed 
      reduced GLP-1 expression, leading to the lower plasma GLP-1 levels, impaired 
      glucose tolerance, and decreased insulin-containing beta cells in pancreatic islets. 
      Our data show that the CREB/CRTC2-dependent transcriptional pathway is critical 
      for regulating glucose homeostasis by controlling production of GLP-1 from the L 
      cells at the level of transcription, maturation, and exocytosis.-Lee, J.-H., Wen, 
      X., Cho, H., Koo, S.-H. CREB/CRTC2 controls GLP-1-dependent regulation of glucose 
      homeostasis.
FAU - Lee, Ji-Hyun
AU  - Lee JH
AD  - Division of Life Sciences, Korea University, Seoul, Korea.
FAU - Wen, Xianlan
AU  - Wen X
AD  - Department of Physiology, Samsung Biomedical Research Institute, Sungkyunkwan 
      University School of Medicine, Suwon, Korea.
FAU - Cho, Hana
AU  - Cho H
AD  - Department of Physiology, Samsung Biomedical Research Institute, Sungkyunkwan 
      University School of Medicine, Suwon, Korea.
FAU - Koo, Seung-Hoi
AU  - Koo SH
AD  - Division of Life Sciences, Korea University, Seoul, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180103
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Crtc2 protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - IY9XDZ35W2 (Glucose)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Calcium Signaling/physiology
MH  - Cell Line
MH  - Enteroendocrine Cells/*metabolism
MH  - Glucagon-Like Peptide 1/genetics/*metabolism
MH  - Glucose/genetics/*metabolism
MH  - Homeostasis/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Oxidative Phosphorylation
MH  - Transcription Factors/genetics/*metabolism
MH  - Transcription, Genetic/physiology
OTO - NOTNLM
OT  - cAMP signaling
OT  - glucose metabolism
OT  - intestinal L cells
OT  - transcriptional activator
EDAT- 2017/11/10 06:00
MHDA- 2018/11/07 06:00
CRDT- 2017/11/10 06:00
PHST- 2017/11/10 06:00 [pubmed]
PHST- 2018/11/07 06:00 [medline]
PHST- 2017/11/10 06:00 [entrez]
AID - fj.201700845R [pii]
AID - 10.1096/fj.201700845R [doi]
PST - ppublish
SO  - FASEB J. 2018 Mar;32(3):1566-1578. doi: 10.1096/fj.201700845R. Epub 2018 Jan 3.