PMID- 17194744
OWN - NLM
STAT- MEDLINE
DCOM- 20070424
LR  - 20220208
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 148
IP  - 4
DP  - 2007 Apr
TI  - Activation of liver X receptors and retinoid X receptors induces growth arrest 
      and apoptosis in insulin-secreting cells.
PG  - 1843-9
AB  - Liver X receptors (LXRs) form functional heterodimers with the retinoid X 
      receptors (RXRs) and regulate cholesterol, lipid, and glucose metabolism. We 
      demonstrated previously that activation of LXR modulates insulin secretion in 
      MIN6 cells and pancreatic islets. In this study we investigated the effects of 
      the LXR agonist T0901317 and the RXR agonist 9-cis-retinoic acid (9cRA) on cell 
      proliferation and apoptosis in MIN6 cells. Whereas T0901317 showed no effect on 
      proliferation of MIN6 cells, combination of T0901317 with 9cRA inhibited cell 
      proliferation. Flow cytometry analysis of cell cycle demonstrated that activation 
      of LXR/RXR prevented MIN6 cells from G1 to G2 phase progression. Combination of 
      T0901317 and 9cRA increased apoptosis rate and caspase-3/7 activity in MIN6 
      cells. Moreover, T0901317 or its combination with 9cRA significantly increased 
      the cell susceptibility to free fatty acid- and cytokine-induced apoptosis. 
      Treatment of MIN6 cells with LXR and RXR agonists produced a strong increase in 
      expression of mothers against decapentaplegic homolog 3, a protein known to 
      inhibit cell cycle G1/S phase progression and induce apoptosis. In isolated rat 
      islets, the effect of palmitic acid on caspase-3/7 activity was increased with 
      T0901317 alone and even more with the combination of T0901317 and 9cRA. Thus, 
      activation of LXR/RXR signaling inhibits cell proliferation and induces apoptosis 
      in pancreatic beta-cells.
FAU - Wente, Wolf
AU  - Wente W
AD  - Lilly Research Laboratories, Essener Bogen 7, D-22419 Hamburg, Germany.
FAU - Brenner, Martin B
AU  - Brenner MB
FAU - Zitzer, Heike
AU  - Zitzer H
FAU - Gromada, Jesper
AU  - Gromada J
FAU - Efanov, Alexander M
AU  - Efanov AM
LA  - eng
PT  - Journal Article
DEP - 20061228
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hydrocarbons, Fluorinated)
RN  - 0 (Liver X Receptors)
RN  - 0 (Orphan Nuclear Receptors)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Sulfonamides)
RN  - 0 (T0901317)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Caspases/metabolism
MH  - *Cell Proliferation
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/agonists/*metabolism
MH  - Hydrocarbons, Fluorinated
MH  - Insulin-Secreting Cells/drug effects/*metabolism
MH  - Liver X Receptors
MH  - Male
MH  - Mice
MH  - Orphan Nuclear Receptors
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Cytoplasmic and Nuclear/agonists/*metabolism
MH  - Retinoid X Receptors/agonists/*metabolism
MH  - Sulfonamides/pharmacology
MH  - Transcriptional Activation
EDAT- 2006/12/30 09:00
MHDA- 2007/04/25 09:00
CRDT- 2006/12/30 09:00
PHST- 2006/12/30 09:00 [pubmed]
PHST- 2007/04/25 09:00 [medline]
PHST- 2006/12/30 09:00 [entrez]
AID - en.2006-1247 [pii]
AID - 10.1210/en.2006-1247 [doi]
PST - ppublish
SO  - Endocrinology. 2007 Apr;148(4):1843-9. doi: 10.1210/en.2006-1247. Epub 2006 Dec 
      28.