PMID- 20798333
OWN - NLM
STAT- MEDLINE
DCOM- 20101116
LR  - 20211020
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 59
IP  - 11
DP  - 2010 Nov
TI  - Nuclear hormone retinoid X receptor (RXR) negatively regulates the 
      glucose-stimulated insulin secretion of pancreatic ss-cells.
PG  - 2854-61
LID - 10.2337/db09-1897 [doi]
AB  - OBJECTIVE: Retinoid X receptors (RXRs) are members of the nuclear hormone 
      receptor superfamily and are thought to be key regulators in differentiation, 
      cellular growth, and gene expression. Although several experiments using 
      pancreatic beta-cell lines have shown that the ligands of nuclear hormone receptors 
      modulate insulin secretion, it is not clear whether RXRs have any role in insulin 
      secretion. RESEARCH DESIGN AND METHODS: To elucidate the function of RXRs in 
      pancreatic beta-cells, we generated a double-transgenic mouse in which a 
      dominant-negative form of RXRbeta was inducibly expressed in pancreatic beta-cells 
      using the Tet-On system. We also established a pancreatic beta-cell line from an 
      insulinoma caused by the beta-cell-specific expression of simian virus 40 T antigen 
      in the above transgenic mouse. RESULTS: In the transgenic mouse, expression of 
      the dominant-negative RXR enhanced the insulin secretion with high glucose 
      stimulation. In the pancreatic beta-cell line, the suppression of RXRs also enhanced 
      glucose-stimulated insulin secretion at a high glucose concentration, while 
      9-cis-retinoic acid, an RXR agonist, repressed it. High-density oligonucleotide 
      microarray analysis showed that expression of the dominant-negative RXR affected 
      the expression levels of a number of genes, some of which have been implicated in 
      the function and/or differentiation of beta-cells. CONCLUSIONS: These results 
      suggest that endogenous RXR negatively regulates the glucose-stimulated insulin 
      secretion. Given these findings, we propose that the modulation of endogenous RXR 
      in beta-cells may be a new therapeutic approach for improving impaired insulin 
      secretion in type 2 diabetes.
FAU - Miyazaki, Satsuki
AU  - Miyazaki S
AD  - Division of Stem Cell Regulation Research, Osaka University Graduate School of 
      Medicine, Osaka, Japan.
FAU - Taniguchi, Hidenori
AU  - Taniguchi H
FAU - Moritoh, Yusuke
AU  - Moritoh Y
FAU - Tashiro, Fumi
AU  - Tashiro F
FAU - Yamamoto, Tsunehiko
AU  - Yamamoto T
FAU - Yamato, Eiji
AU  - Yamato E
FAU - Ikegami, Hiroshi
AU  - Ikegami H
FAU - Ozato, Keiko
AU  - Ozato K
FAU - Miyazaki, Jun-ichi
AU  - Miyazaki J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100826
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Complementary)
RN  - 0 (Insulin)
RN  - 0 (Retinoid X Receptor alpha)
RN  - 0 (Retinoid X Receptor beta)
RN  - 0 (Retinoid X Receptors)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Conserved Sequence
MH  - Crosses, Genetic
MH  - DNA Primers
MH  - DNA, Complementary/genetics
MH  - Female
MH  - Glucose/*pharmacology
MH  - Humans
MH  - Insulin/genetics/*metabolism
MH  - Insulin Secretion
MH  - Insulin-Secreting Cells/drug effects/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Promoter Regions, Genetic
MH  - Retinoid X Receptor alpha/genetics/physiology
MH  - Retinoid X Receptor beta/genetics/physiology
MH  - Retinoid X Receptors/genetics/*physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC2963544
EDAT- 2010/08/28 06:00
MHDA- 2010/11/17 06:00
PMCR- 2011/11/01
CRDT- 2010/08/28 06:00
PHST- 2010/08/28 06:00 [entrez]
PHST- 2010/08/28 06:00 [pubmed]
PHST- 2010/11/17 06:00 [medline]
PHST- 2011/11/01 00:00 [pmc-release]
AID - db09-1897 [pii]
AID - 1897 [pii]
AID - 10.2337/db09-1897 [doi]
PST - ppublish
SO  - Diabetes. 2010 Nov;59(11):2854-61. doi: 10.2337/db09-1897. Epub 2010 Aug 26.