Ignet

Gene Information

Gene symbol: RXRA

Gene name: retinoid X receptor, alpha

HGNC ID: 10477

Synonyms: NR2B1

Related Genes

#	Gene Symbol	Number of hits
1	ABCA1	1 hits
2	ADIPOQ	1 hits
3	AHR	1 hits
4	AKT1	1 hits
5	ARNT	1 hits
6	CAP1	1 hits
7	CAT	1 hits
8	CBL	1 hits
9	CCL2	1 hits
10	CD46	1 hits
11	CEBPA	1 hits
12	CETP	1 hits
13	CRABP1	1 hits
14	CYP2B6	1 hits
15	DR1	1 hits
16	FABP2	1 hits
17	GRIP1	1 hits
18	GTF3A	1 hits
19	GZMB	1 hits
20	HNF4A	1 hits
21	HNRNPC	1 hits
22	IGFALS	1 hits
23	IGFBP1	1 hits
24	IGFBP3	1 hits
25	INS	1 hits
26	INSIG2	1 hits
27	LEP	1 hits
28	LIPE	1 hits
29	MAPK1	1 hits
30	MED1	1 hits
31	MMP9	1 hits
32	NCOA1	1 hits
33	NCOA2	1 hits
34	NCOR2	1 hits
35	NPHS1	1 hits
36	NPPA	1 hits
37	NR1H3	1 hits
38	NR1H4	1 hits
39	PCK2	1 hits
40	PI3	1 hits
41	PIK3CG	1 hits
42	PPARA	1 hits
43	PPARG	1 hits
44	PPARGC1A	1 hits
45	PTPN1	1 hits
46	RARA	1 hits
47	RBP1	1 hits
48	RPS27A	1 hits
49	RXRB	1 hits
50	SCP2	1 hits
51	SLC2A2	1 hits
52	SLC2A4	1 hits
53	TBXAS1	1 hits
54	THRB	1 hits
55	TIMP1	1 hits
56	TNF	1 hits
57	TXNRD2	1 hits
58	UCHL1	1 hits
59	VDR	1 hits

Related Sentences

#	PMID	Sentence
1	8981016	Periodically hyperthyroid phenotype in thyroid hormone resistance is associated with mutation D322N in the thyroid hormone receptor beta gene: transcriptional properties of the mutant and the role of retinoid X receptor.
2	8981016	TR beta-CN could not be activated by retinoid X receptor (RXR) beta in the presence of T3, whereas addition of 9cis-retinoic acid (9c-RA) resulted in the transactivation of TRE-PAL through RXR beta independently of the presence of TR beta-CN.
3	8981016	Periodically hyperthyroid phenotype in thyroid hormone resistance is associated with mutation D322N in the thyroid hormone receptor beta gene: transcriptional properties of the mutant and the role of retinoid X receptor.
4	8981016	TR beta-CN could not be activated by retinoid X receptor (RXR) beta in the presence of T3, whereas addition of 9cis-retinoic acid (9c-RA) resulted in the transactivation of TRE-PAL through RXR beta independently of the presence of TR beta-CN.
5	9065481	Identification, characterization, and tissue distribution of human peroxisome proliferator-activated receptor (PPAR) isoforms PPARgamma2 versus PPARgamma1 and activation with retinoid X receptor agonists and antagonists.
6	9065481	Human PPARgamma binds to DNA as a heterodimer with the retinoid X receptor (RXR).
7	9065481	Identification, characterization, and tissue distribution of human peroxisome proliferator-activated receptor (PPAR) isoforms PPARgamma2 versus PPARgamma1 and activation with retinoid X receptor agonists and antagonists.
8	9065481	Human PPARgamma binds to DNA as a heterodimer with the retinoid X receptor (RXR).
9	9121558	Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists.
10	9121558	Retinoic acid receptors (RAR), thyroid hormone receptors (TR), peroxisome proliferator activated receptors (PPARs) and the orphan receptor, LXR, bind preferentially to DNA as heterodimers with a common partner, retinoid X receptor (RXR), to regulate transcription.
11	9121558	We demonstrate here that RXR-selective ligands (referred to as rexinoids) function as RXR heterodimer-selective agonists, activating RXR: PPARgamma and RXR:LXR dimers but not RXR:RAR or RXR:TR heterodimers.
12	9121558	Because PPARgamma is a target for antidiabetic agents, we investigated whether RXR ligands could alter insulin and glucose signalling.
13	9121558	These data suggest that the RXR:PPARgamma heterodimer is a single-function complex serving as a molecular target for treatment of insulin resistance.
14	9121558	Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists.
15	9121558	Retinoic acid receptors (RAR), thyroid hormone receptors (TR), peroxisome proliferator activated receptors (PPARs) and the orphan receptor, LXR, bind preferentially to DNA as heterodimers with a common partner, retinoid X receptor (RXR), to regulate transcription.
16	9121558	We demonstrate here that RXR-selective ligands (referred to as rexinoids) function as RXR heterodimer-selective agonists, activating RXR: PPARgamma and RXR:LXR dimers but not RXR:RAR or RXR:TR heterodimers.
17	9121558	Because PPARgamma is a target for antidiabetic agents, we investigated whether RXR ligands could alter insulin and glucose signalling.
18	9121558	These data suggest that the RXR:PPARgamma heterodimer is a single-function complex serving as a molecular target for treatment of insulin resistance.
19	9492033	Regulation of leptin promoter function by Sp1, C/EBP, and a novel factor.
20	9492033	No effect on the transient expression of leptin was noted upon treatment with a thiazolidinedione, BRL49653, or upon cotransfection with peroxisome proliferator-activated receptor-gamma/retinoid X receptor-alpha or sterol response element-binding protein-1.
21	9492033	Mutations of the Sp1, LP1, and C/EBP sites in pairwise combinations diminished promoter activity to the extent predicted assuming these motifs contribute independently to leptin promoter function.
22	9652687	The catalytic region of HIV-1 protease, to which protease inhibitors bind, has approximately 60% homology to regions within two proteins that regulate lipid metabolism: cytoplasmic retinoic-acid binding protein type 1 (CRABP-1) and low density lipoprotein-receptor-related protein (LRP).
23	9652687	We hypothesise that protease inhibitors inhibit CRABP-1-modified, and cytochrome P450 3A-mediated synthesis of cis-9-retinoic acid, a key activator of the retinoid X receptor; and peroxisome proliferator activated receptor type gamma (PPAR-gamma) heterodimer, an adipocyte receptor that regulates peripheral adipocyte differentiation and apoptosis.
24	9652687	Protease-inhibitor binding to LRP would impair hepatic chylomicron uptake and triglyceride clearance by the endothelial LRP-lipoprotein lipase complex.
25	9671776	Expression of peroxisome proliferator-activated receptor alpha (PPARalpha) and enzymes of fatty acid (FA) oxidation is markedly reduced in the fat-laden, dysfunctional islets of obese, prediabetic Zucker diabetic fatty (fa/fa) rats with mutated leptin receptors (OB-R).
26	9671776	Leptin, PPARalpha/retinoid x receptor ligands, and FA all up-regulate PPARalpha and enzymes of FA oxidation and stimulate [3H]-palmitate oxidation in normal islets but not in islets from fa/fa rats.
27	9751766	Overexpression of leptin receptors in pancreatic islets of Zucker diabetic fatty rats restores GLUT-2, glucokinase, and glucose-stimulated insulin secretion.
28	9751766	The high-Km glucose transporter, GLUT-2, and the high-Km hexokinase of beta cells, glucokinase (GK), are required for glucose-stimulated insulin secretion (GSIS).
29	9751766	Leptin induced a rise in phosphorylated STAT3, indicating that the transferred wild-type OB-R was functional.
30	9751766	GLUT-2 protein rose 17-fold in AdCMV-OB-Rb-treated ZDF islets without leptin, and leptin caused no further rise.
31	9751766	Clofibrate and 9-cis-retinoic acid, the partner ligands for binding to peroxisome proliferator-activator receptor alpha (PPARalpha) and retinoid X receptor, up-regulated GLUT-2 expression in islets of normal rats, but not in ZDF rats, in which PPARalpha is very low.
32	9751766	Because the fat content of islets of diabetic ZDF rats remains high unless they are treated with leptin, it appears that restoration of GSIS requires normalization of intracellular nutrient homeostasis, whereas up-regulation of GLUT-2 and GK is leptin-independent, requiring only high expression of OB-Rb.
33	9830040	PPARalpha/retinoid X receptor alpha formed specific complexes with oligonucleotides containing the FARE, and anti-PPARalpha antibody shifted nuclear protein-DNA complexes, confirming the role of this factor in regulating the expression of this critical metabolic enzyme gene.
34	10076998	A novel method for analysis of nuclear receptor function at natural promoters: peroxisome proliferator-activated receptor gamma agonist actions on aP2 gene expression detected using branched DNA messenger RNA quantitation.
35	10076998	PPARgamma activates many target genes involved in lipid anabolism including the adipocyte fatty acid binding protein (aP2).
36	10076998	In this study, induction of aP2 gene expression by PPARgamma agonists was examined in both cultured cells and diabetic mice using branched DNA (bDNA)-mediated mRNA quantitation. bDNA technology allows for the direct measurement of a particular mRNA directly within cellular lysate using a 96-well plate format in a time frame comparable to a reporter gene assay.
37	10076998	A natural PPARgamma ligand, 15-deoxy-delta12,14-PGJ2, was also active in this assay with a maximal induction of aP2 mRNA of approximately 5-fold when tested at 1 microM.
38	10076998	Since the PPARgamma:retinoid X receptor (RXR) heterodimer has been characterized as a permissive heterodimer with respect to RXR ligands, the ability of 9-cis-retinoic acid (9-cis-RA) to induce aP2 mRNA was examined.
39	10487716	The CGL1 critical region harbors a plausible candidate gene encoding the retinoid X receptor alpha (RXRA) that plays a central role in adipocyte differentiation.
40	10487716	Identification of the CGL gene(s) will contribute to our understanding of the adipocyte differentiation and elucidation of the mechanisms of insulin resistance in disorders of adipose tissue.
41	10882139	Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors.
42	10882139	The nuclear receptor PPARgamma/RXRalpha heterodimer regulates glucose and lipid homeostasis and is the target for the antidiabetic drugs GI262570 and the thiazolidinediones (TZDs).
43	10882139	We report the crystal structures of the PPARgamma and RXRalpha LBDs complexed to the RXR ligand 9-cis-retinoic acid (9cRA), the PPARgamma agonist rosiglitazone or GI262570, and coactivator peptides.
44	10882139	The PPARgamma/RXRalpha heterodimer is asymmetric, with each LBD deviated approximately 10 degrees from the C2 symmetry, allowing the PPARgamma AF-2 helix to interact with helices 7 and 10 of RXRalpha.
45	10882139	The heterodimer interface is composed of conserved motifs in PPARgamma and RXRalpha that form a coiled coil along helix 10 with additional charge interactions from helices 7 and 9.
46	10882139	The structures provide a molecular understanding of the ability of RXR to heterodimerize with many nuclear receptors and of the permissive activation of the PPARgamma/RXRbeta heterodimer by 9cRA.
47	10882139	Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors.
48	10882139	The nuclear receptor PPARgamma/RXRalpha heterodimer regulates glucose and lipid homeostasis and is the target for the antidiabetic drugs GI262570 and the thiazolidinediones (TZDs).
49	10882139	We report the crystal structures of the PPARgamma and RXRalpha LBDs complexed to the RXR ligand 9-cis-retinoic acid (9cRA), the PPARgamma agonist rosiglitazone or GI262570, and coactivator peptides.
50	10882139	The PPARgamma/RXRalpha heterodimer is asymmetric, with each LBD deviated approximately 10 degrees from the C2 symmetry, allowing the PPARgamma AF-2 helix to interact with helices 7 and 10 of RXRalpha.
51	10882139	The heterodimer interface is composed of conserved motifs in PPARgamma and RXRalpha that form a coiled coil along helix 10 with additional charge interactions from helices 7 and 9.
52	10882139	The structures provide a molecular understanding of the ability of RXR to heterodimerize with many nuclear receptors and of the permissive activation of the PPARgamma/RXRbeta heterodimer by 9cRA.
53	10882139	Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors.
54	10882139	The nuclear receptor PPARgamma/RXRalpha heterodimer regulates glucose and lipid homeostasis and is the target for the antidiabetic drugs GI262570 and the thiazolidinediones (TZDs).
55	10882139	We report the crystal structures of the PPARgamma and RXRalpha LBDs complexed to the RXR ligand 9-cis-retinoic acid (9cRA), the PPARgamma agonist rosiglitazone or GI262570, and coactivator peptides.
56	10882139	The PPARgamma/RXRalpha heterodimer is asymmetric, with each LBD deviated approximately 10 degrees from the C2 symmetry, allowing the PPARgamma AF-2 helix to interact with helices 7 and 10 of RXRalpha.
57	10882139	The heterodimer interface is composed of conserved motifs in PPARgamma and RXRalpha that form a coiled coil along helix 10 with additional charge interactions from helices 7 and 9.
58	10882139	The structures provide a molecular understanding of the ability of RXR to heterodimerize with many nuclear receptors and of the permissive activation of the PPARgamma/RXRbeta heterodimer by 9cRA.
59	10882139	Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors.
60	10882139	The nuclear receptor PPARgamma/RXRalpha heterodimer regulates glucose and lipid homeostasis and is the target for the antidiabetic drugs GI262570 and the thiazolidinediones (TZDs).
61	10882139	We report the crystal structures of the PPARgamma and RXRalpha LBDs complexed to the RXR ligand 9-cis-retinoic acid (9cRA), the PPARgamma agonist rosiglitazone or GI262570, and coactivator peptides.
62	10882139	The PPARgamma/RXRalpha heterodimer is asymmetric, with each LBD deviated approximately 10 degrees from the C2 symmetry, allowing the PPARgamma AF-2 helix to interact with helices 7 and 10 of RXRalpha.
63	10882139	The heterodimer interface is composed of conserved motifs in PPARgamma and RXRalpha that form a coiled coil along helix 10 with additional charge interactions from helices 7 and 9.
64	10882139	The structures provide a molecular understanding of the ability of RXR to heterodimerize with many nuclear receptors and of the permissive activation of the PPARgamma/RXRbeta heterodimer by 9cRA.
65	10882139	Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors.
66	10882139	The nuclear receptor PPARgamma/RXRalpha heterodimer regulates glucose and lipid homeostasis and is the target for the antidiabetic drugs GI262570 and the thiazolidinediones (TZDs).
67	10882139	We report the crystal structures of the PPARgamma and RXRalpha LBDs complexed to the RXR ligand 9-cis-retinoic acid (9cRA), the PPARgamma agonist rosiglitazone or GI262570, and coactivator peptides.
68	10882139	The PPARgamma/RXRalpha heterodimer is asymmetric, with each LBD deviated approximately 10 degrees from the C2 symmetry, allowing the PPARgamma AF-2 helix to interact with helices 7 and 10 of RXRalpha.
69	10882139	The heterodimer interface is composed of conserved motifs in PPARgamma and RXRalpha that form a coiled coil along helix 10 with additional charge interactions from helices 7 and 9.
70	10882139	The structures provide a molecular understanding of the ability of RXR to heterodimerize with many nuclear receptors and of the permissive activation of the PPARgamma/RXRbeta heterodimer by 9cRA.
71	10935544	RXR-PPARgamma (retinoid X receptor-peroxisome proliferator-activated receptor-gamma) heterodimers play important roles in adipocyte and macrophage differentiation and have been implicated as therapeutic targets in diabetes, atherosclerosis, and cancer.
72	10936484	Peroxisome proliferator-activated receptor and retinoid X receptor ligands inhibit monocyte chemotactic protein-1-directed migration of monocytes.
73	10936484	We studied the effects of peroxisome proliferator-activated receptor (PPAR) gamma, alpha, and retinoid X receptor alpha (RXRalpha) ligands on MCP-1-directed migration and matrix metalloproteinase expression of a human acute monocytic leukemia cell line (THP-1).
74	10936484	PPARgamma ligands attenuated MCP-1-induced migration, with 50% inhibition (IC(50)) at 2.8 microM for troglitazone and 4.8 microM for rosiglitazone.
75	10936484	PPARalpha ligands WY-14643 (IC(50): 0.9 microM) and 5,8,11,14-eicosatetranoic acid (IC(50): 9.9 microM), and the potent RXRalpha ligand AGN 4204 (IC(50): 3.6 nM) also blocked monocyte migration.
76	10936484	AGN 4204 increased PMA-induced tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) expression, whereas all PPAR ligands showed no effect.
77	10936484	All PPAR and RXRalpha ligands blocked chemotaxis of THP-1 monocytes in the absence of a matrix barrier.
78	10936484	This study demonstrates that activated PPARs and RXRalpha, block MCP-1-directed monocyte migration, mediated, at least in part, through their effects on matrix metalloproteinase-9 or TIMP-1 production, or chemotaxis.
79	10936484	Peroxisome proliferator-activated receptor and retinoid X receptor ligands inhibit monocyte chemotactic protein-1-directed migration of monocytes.
80	10936484	We studied the effects of peroxisome proliferator-activated receptor (PPAR) gamma, alpha, and retinoid X receptor alpha (RXRalpha) ligands on MCP-1-directed migration and matrix metalloproteinase expression of a human acute monocytic leukemia cell line (THP-1).
81	10936484	PPARgamma ligands attenuated MCP-1-induced migration, with 50% inhibition (IC(50)) at 2.8 microM for troglitazone and 4.8 microM for rosiglitazone.
82	10936484	PPARalpha ligands WY-14643 (IC(50): 0.9 microM) and 5,8,11,14-eicosatetranoic acid (IC(50): 9.9 microM), and the potent RXRalpha ligand AGN 4204 (IC(50): 3.6 nM) also blocked monocyte migration.
83	10936484	AGN 4204 increased PMA-induced tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) expression, whereas all PPAR ligands showed no effect.
84	10936484	All PPAR and RXRalpha ligands blocked chemotaxis of THP-1 monocytes in the absence of a matrix barrier.
85	10936484	This study demonstrates that activated PPARs and RXRalpha, block MCP-1-directed monocyte migration, mediated, at least in part, through their effects on matrix metalloproteinase-9 or TIMP-1 production, or chemotaxis.
86	10936484	Peroxisome proliferator-activated receptor and retinoid X receptor ligands inhibit monocyte chemotactic protein-1-directed migration of monocytes.
87	10936484	We studied the effects of peroxisome proliferator-activated receptor (PPAR) gamma, alpha, and retinoid X receptor alpha (RXRalpha) ligands on MCP-1-directed migration and matrix metalloproteinase expression of a human acute monocytic leukemia cell line (THP-1).
88	10936484	PPARgamma ligands attenuated MCP-1-induced migration, with 50% inhibition (IC(50)) at 2.8 microM for troglitazone and 4.8 microM for rosiglitazone.
89	10936484	PPARalpha ligands WY-14643 (IC(50): 0.9 microM) and 5,8,11,14-eicosatetranoic acid (IC(50): 9.9 microM), and the potent RXRalpha ligand AGN 4204 (IC(50): 3.6 nM) also blocked monocyte migration.
90	10936484	AGN 4204 increased PMA-induced tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) expression, whereas all PPAR ligands showed no effect.
91	10936484	All PPAR and RXRalpha ligands blocked chemotaxis of THP-1 monocytes in the absence of a matrix barrier.
92	10936484	This study demonstrates that activated PPARs and RXRalpha, block MCP-1-directed monocyte migration, mediated, at least in part, through their effects on matrix metalloproteinase-9 or TIMP-1 production, or chemotaxis.
93	10936484	Peroxisome proliferator-activated receptor and retinoid X receptor ligands inhibit monocyte chemotactic protein-1-directed migration of monocytes.
94	10936484	We studied the effects of peroxisome proliferator-activated receptor (PPAR) gamma, alpha, and retinoid X receptor alpha (RXRalpha) ligands on MCP-1-directed migration and matrix metalloproteinase expression of a human acute monocytic leukemia cell line (THP-1).
95	10936484	PPARgamma ligands attenuated MCP-1-induced migration, with 50% inhibition (IC(50)) at 2.8 microM for troglitazone and 4.8 microM for rosiglitazone.
96	10936484	PPARalpha ligands WY-14643 (IC(50): 0.9 microM) and 5,8,11,14-eicosatetranoic acid (IC(50): 9.9 microM), and the potent RXRalpha ligand AGN 4204 (IC(50): 3.6 nM) also blocked monocyte migration.
97	10936484	AGN 4204 increased PMA-induced tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) expression, whereas all PPAR ligands showed no effect.
98	10936484	All PPAR and RXRalpha ligands blocked chemotaxis of THP-1 monocytes in the absence of a matrix barrier.
99	10936484	This study demonstrates that activated PPARs and RXRalpha, block MCP-1-directed monocyte migration, mediated, at least in part, through their effects on matrix metalloproteinase-9 or TIMP-1 production, or chemotaxis.
100	10936484	Peroxisome proliferator-activated receptor and retinoid X receptor ligands inhibit monocyte chemotactic protein-1-directed migration of monocytes.
101	10936484	We studied the effects of peroxisome proliferator-activated receptor (PPAR) gamma, alpha, and retinoid X receptor alpha (RXRalpha) ligands on MCP-1-directed migration and matrix metalloproteinase expression of a human acute monocytic leukemia cell line (THP-1).
102	10936484	PPARgamma ligands attenuated MCP-1-induced migration, with 50% inhibition (IC(50)) at 2.8 microM for troglitazone and 4.8 microM for rosiglitazone.
103	10936484	PPARalpha ligands WY-14643 (IC(50): 0.9 microM) and 5,8,11,14-eicosatetranoic acid (IC(50): 9.9 microM), and the potent RXRalpha ligand AGN 4204 (IC(50): 3.6 nM) also blocked monocyte migration.
104	10936484	AGN 4204 increased PMA-induced tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) expression, whereas all PPAR ligands showed no effect.
105	10936484	All PPAR and RXRalpha ligands blocked chemotaxis of THP-1 monocytes in the absence of a matrix barrier.
106	10936484	This study demonstrates that activated PPARs and RXRalpha, block MCP-1-directed monocyte migration, mediated, at least in part, through their effects on matrix metalloproteinase-9 or TIMP-1 production, or chemotaxis.
107	10969836	Promoter activities were increased by coexpression of peroxisomal proliferator-activated receptor (PPAR)-gamma, retinoid X receptor (RXR)-alpha, and treatment of their ligands; troglitazone and 9-cis retinoic acid potentiated the transactivational effects.
108	10969836	Introduction of mutations in GLUT2-PPRE resulted in loss of transactivational effects of the PPAR-gamma/RXR-alpha heterodimer.
109	10969836	Electrophoretic mobility shift assay using nuclear extracts of CV-1 cells, which were transfected with various combinations of PPARs or RXR-alpha expression plasmids, revealed that heterodimers of PPAR-gamma and RXR-alpha preferentially bound to GLUT2-PPRE.
110	10969836	Promoter activities were increased by coexpression of peroxisomal proliferator-activated receptor (PPAR)-gamma, retinoid X receptor (RXR)-alpha, and treatment of their ligands; troglitazone and 9-cis retinoic acid potentiated the transactivational effects.
111	10969836	Introduction of mutations in GLUT2-PPRE resulted in loss of transactivational effects of the PPAR-gamma/RXR-alpha heterodimer.
112	10969836	Electrophoretic mobility shift assay using nuclear extracts of CV-1 cells, which were transfected with various combinations of PPARs or RXR-alpha expression plasmids, revealed that heterodimers of PPAR-gamma and RXR-alpha preferentially bound to GLUT2-PPRE.
113	10969836	Promoter activities were increased by coexpression of peroxisomal proliferator-activated receptor (PPAR)-gamma, retinoid X receptor (RXR)-alpha, and treatment of their ligands; troglitazone and 9-cis retinoic acid potentiated the transactivational effects.
114	10969836	Introduction of mutations in GLUT2-PPRE resulted in loss of transactivational effects of the PPAR-gamma/RXR-alpha heterodimer.
115	10969836	Electrophoretic mobility shift assay using nuclear extracts of CV-1 cells, which were transfected with various combinations of PPARs or RXR-alpha expression plasmids, revealed that heterodimers of PPAR-gamma and RXR-alpha preferentially bound to GLUT2-PPRE.
116	10976920	A selective peroxisome proliferator-activated receptor-gamma (PPARgamma) modulator blocks adipocyte differentiation but stimulates glucose uptake in 3T3-L1 adipocytes.
117	10976920	Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists such as the thiazolidinediones are insulin sensitizers used in the treatment of type 2 diabetes.
118	10976920	We have identified a novel PPARgamma ligand, LG100641, that does not activate PPARgamma but selectively and competitively blocks thiazolidinedione-induced PPARgamma activation and adipocyte conversion.
119	10976920	This novel PPARgamma antagonist does not block adipocyte differentiation induced by a ligand for the retinoid X receptor (RXR), the heterodimeric partner for PPARgamma, or by a differentiation cocktail containing insulin, dexamethasone, and 1-methyl-3-isobutylxanthine.
120	10976920	Such selective PPARgamma antagonists may help determine whether insulin sensitization by thiazolidinediones is mediated solely through PPARgamma activation, and whether there are PPARgamma-ligand-independent pathways for adipocyte differentiation.
121	10976920	If selective PPARgamma modulators block adipogenesis in vivo, they may prevent obesity, lower insulin resistance, and delay the onset of type 2 diabetes.
122	10993727	Hepatocyte nuclear factor 4alpha (HNF4alpha) (NR2A1), an orphan member of the nuclear receptor superfamily, binds DNA exclusively as a homodimer even though it is very similar in amino acid sequence to retinoid X receptor alpha (RXRalpha), which heterodimerizes readily with other receptors.
123	10993727	When K300 (in helix 9) and E327 (in helix 10) of HNF4alpha1 were converted to the analogous residues in RXRalpha (E390 and K417, respectively) the resulting construct did not heterodimerize with the wild-type HNF4alpha, although it was still able to form homodimers and bind DNA.
124	10993727	Furthermore, the double mutant did not heterodimerize with RXR or RAR but was still able to dimerize in solution with an HNF4alpha construct truncated at amino acid residue 268.
125	10993727	Hepatocyte nuclear factor 4alpha (HNF4alpha) (NR2A1), an orphan member of the nuclear receptor superfamily, binds DNA exclusively as a homodimer even though it is very similar in amino acid sequence to retinoid X receptor alpha (RXRalpha), which heterodimerizes readily with other receptors.
126	10993727	When K300 (in helix 9) and E327 (in helix 10) of HNF4alpha1 were converted to the analogous residues in RXRalpha (E390 and K417, respectively) the resulting construct did not heterodimerize with the wild-type HNF4alpha, although it was still able to form homodimers and bind DNA.
127	10993727	Furthermore, the double mutant did not heterodimerize with RXR or RAR but was still able to dimerize in solution with an HNF4alpha construct truncated at amino acid residue 268.
128	11259621	Both retinoid X receptor (RXR)-selective agonists (rexinoids) and thiazolidinediones (TZDs), PPAR (peroxisome proliferator-activated receptor)-gamma-specific ligands, produce insulin sensitization in diabetic rodents.
129	11259621	In adipose tissue, rosiglitazone decreased tumor necrosis factor-alpha (TNF-alpha) mRNA and induced glucose transporter 4 (GLUT4), muscle carnitine palmitoyl-transferase (MCPT), stearoyl CoA desaturase (SCD1), and fatty acid translocase (CD36).
130	11259621	In contrast, LG100268 increased TNF-alpha and had no effect or suppressed the expression of GLUT4, MCPT, SCD1, and CD36.
131	11259621	In liver, the rexinoid increased MCPT, SCD1, and CD36 mRNAs, whereas rosiglitazone induced only a small increase in CD36.
132	11259621	In skeletal muscle, rosiglitazone and LG100268 have similar effects; both increased SCD1 and CD36 mRNAs.
133	11327101	PPARgamma is the best characterized of the PPARs.
134	11327101	The heterodimer of PPARgamma with the retinoid X receptor (RXR) plays a crucial role in adipogenesis and insulin sensitization.
135	11327101	PPARgamma is activated by a number of naturally occurring fatty acid derivatives and by several synthetic compounds, including the thiazolidinediones and L-tyrosine-based insulin sensitizers.
136	11357475	Peroxisome proliferator-activated receptor (PPAR) gamma and retinoid X receptor (RXR) agonists have complementary effects on glucose and lipid metabolism in human skeletal muscle.
137	11425290	Synthetic ligands of the retinoid X receptor (RXR) have shown antidiabetic activity in mice, apparently owing to the fact that they stimulate the transcriptional activity of PPAR-gamma/RXR heterodimers, much like thiazolidinedione drugs.
138	11436190	Retinoid X receptor (RXR) is a nuclear receptor that functions as an obligate heterodimeric partner of peroxisome proliferator-activator receptor (PPAR).
139	11436190	Studies have shown that the alpha isoform of RXR and PPARgamma act synergistically to regulate gene expression and insulin action.
140	11697231	PPAR gamma/RXR as a molecular target for diabetes.
141	11697231	Novel therapies that improve insulin action include ligands that bind and activate the nuclear receptors peroxisome proliferator activating receptor gamma (PPAR gamma) and retinoid X receptor (RXR).
142	11697231	PPAR gamma/RXR form heterodimers that regulate transcription of genes involved in insulin action, adipocyte differentiation, lipid metabolism and inflammation.
143	11697231	PPAR gamma activators include prostanoids, fatty acids, thiazolidinediones and N-(2-benzoylphenyl)tyrosine analogues.
144	11697231	Although adipose tissue mediates some of the effects of PPAR gamma/RXR ligands, other tissues also regulate the effects of these receptors.
145	11697231	The activity of the PPAR gamma/RXR heterodimer is influenced by posttranslational modifications, receptor turnover, polymorphisms, splice variants, coactivators and corepressors.
146	11697231	This article reviews recent developments in research on these receptors, with particular emphasis on metabolic effects, ligand selectivity, structure and regulation of the PPAR gamma/RXR heterodimer.
147	11729635	[PPAR gamma agonist and antagonist].
148	11729635	Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a ligand-activated transcription factor and functions as a heterodimer with a retinoid X receptor (RXR).
149	11729635	Supraphysiological activation of PPAR gamma by thiazolidinediones can reduce insulin resistance and hyperglycemia in type 2 diabetes, but these drugs can also cause weight gain.
150	11729635	Quite unexpectedly, a moderate reduction of PPAR gamma activity observed in heterozygous PPAR gamma-deficient mice or the Pro 12 Ala polymorphism in human PPAR gamma has been shown to prevent insulin resistance and obesity induced by a high-fat (HF) diet.
151	11729635	We investigated whether functional antagonism toward PPAR gamma/RXR could be used to treat obesity and type 2 diabetes.
152	11729635	We show herein that moderate reduction of PPAR gamma with an RXR antagonist or a PPAR gamma antagonist decreases triglyceride (TG) content in white adipose tissue, skeletal muscle and liver.
153	11729635	These inhibitors potentiate leptin's effects and stimulated adiponectin levels, which increases fatty acid combustion and energy dissipation, thereby ameliorating HF diet-induced obesity and insulin resistance.
154	11729635	Paradoxically, severe reduction of PPAR gamma by treatment of heterozygous PPAR gamma-deficient mice with an RXR antagonist or a PPAR gamma antagonist depletes white adipose tissue and markedly decreases leptin and adiponectin levels and energy dissipation, which increases TG content in skeletal muscle and the liver, thereby leading to the re-emergence of insulin resistance.
155	11729635	Our data suggest that appropriate functional antagonism of PPAR gamma/RXR may be a logical approach to protection against obesity and related diseases such as type 2 diabetes.
156	11772294	Agents that have potent HDL cholesterol raising capacity include cholesteryl ester transfer protein (CETP) inhibitors, retinoid X receptor (RXR) selective agonists, specific peroxisome proliferator-activated receptor (PPAR) agonists and oestrogen-like compounds.
157	11772294	Another area of development involves agents that will lower both cholesterol and triglyceride levels, such as partial inhibitors of microsomal triglyceride transfer protein (MTP) and perhaps squalene synthase inhibitors and agonists of AMP kinase.
158	11809858	The pan-retinoic acid receptor antagonist AGN 193109 has been previously reported to elevate CYP1A1 levels, implicating the aryl hydrocarbon receptor (AhR) as an additional target for this retinoid.
159	11809858	AhR is a cytosolic ligand-dependent transcription factor that, in conjunction with the AhR nuclear translocator (Arnt), binds to dioxin response elements (DREs) located in the promoter region of target genes, such as CYP1A1, and induces their transcription.
160	11809858	The sum of the data demonstrates that some synthetic retinoids in addition to activating the retinoic acid receptor/retinoid X receptor pathway are capable of binding to AhR and activating the AhR/Arnt pathway.
161	11818483	The peroxisome proliferator-activated receptors (PPARs) are a group of three nuclear receptor isoforms, PPAR gamma, PPAR alpha, and PPAR delta, encoded by different genes.
162	11818483	PPARs bind as heterodimers with a retinoid X receptor and, upon binding agonist, interact with cofactors such that the rate of transcription initiation is increased.
163	11872666	Thiazolidinediones, synthetic ligands of peroxisomal proliferator-activated receptor-gamma (PPAR-gamma), improve peripheral insulin sensitivity and glucose-stimulated insulin secretion in pancreatic beta-cells.
164	11872666	To explore the role of PPAR-gamma in glucose sensing of beta-cells, we have dissected the beta-cell-specific glucokinase (betaGK) promoter, which constitutes glucose-sensing apparatus in pancreatic beta-cells, and identified a peroxisomal proliferator response element (PPRE) in the promoter.
165	11872666	PPAR-gamma/retinoid X receptor-alpha heterodimer binds to the element and activates the betaGK promoter.
166	11872672	Regional differences in the response of human pre-adipocytes to PPARgamma and RXRalpha agonists.
167	11872672	To explore these site-related differences further, we used real-time RT-PCR to quantify the specific mRNAs encoding peroxisome proliferator-activated receptor (PPAR) gamma1 and gamma2 and found that both isoforms were more highly expressed in SC than in OM preadipocytes.
168	11872672	To establish whether the refractoriness of OM preadipocytes to differentiation was unique to activators of the PPARgamma pathway, we examined the effects of the retinoid X receptor (RXR) ligand LG100268.
169	11872672	Regional differences in the response of human pre-adipocytes to PPARgamma and RXRalpha agonists.
170	11872672	To explore these site-related differences further, we used real-time RT-PCR to quantify the specific mRNAs encoding peroxisome proliferator-activated receptor (PPAR) gamma1 and gamma2 and found that both isoforms were more highly expressed in SC than in OM preadipocytes.
171	11872672	To establish whether the refractoriness of OM preadipocytes to differentiation was unique to activators of the PPARgamma pathway, we examined the effects of the retinoid X receptor (RXR) ligand LG100268.
172	11877384	Surprisingly, LG100754 has minimal intrinsic transcriptional activity, instead it enhances the potency of proliferator-activated receptor (PPAR) gamma-retinoid X receptor heterodimers for PPARgamma ligands.
173	11877384	The ability of LG100754 to both increase PPARgamma sensitivity and relieve insulin resistance implies that a deficiency in endogenous PPARgamma ligands may represent an early step in the development of insulin resistance.
174	11978627	Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB activation by TNF-alpha is obligatory.
175	11978627	Tumor necrosis factor-alpha (TNF-alpha) is a contributing cause of the insulin resistance seen in obesity and obesity-linked type 2 diabetes, but the mechanism(s) by which TNF-alpha induces insulin resistance is not understood.
176	11978627	TNF-alpha-induced genes include transcription factors implicated in preadipocyte gene expression or NF-kappaB activation, cytokines and cytokine-induced proteins, growth factors, enzymes, and signaling molecules.
177	11978627	Importantly, a number of adipocyte-abundant genes, including GLUT4, hormone sensitive lipase, long-chain fatty acyl-CoA synthase, adipocyte complement-related protein of 30 kDa, and transcription factors CCAAT/enhancer binding protein-alpha, receptor retinoid X receptor-alpha, and peroxisome profilerator-activated receptor gamma were significantly downregulated by TNF-alpha treatment.
178	11978627	Correspondingly, 24-h exposure of 3T3-L1 adipocytes to TNF-alpha resulted in reduced protein levels of GLUT4 and several insulin signaling proteins, including the insulin receptor, insulin receptor substrate 1 (IRS-1), and protein kinase B (AKT).
179	11978627	Nuclear factor-kappaB (NF-kappaB) was activated within 15 min of TNF-alpha addition. 3T3-L1 adipocytes expressing IkappaBalpha-DN, a nondegradable NF-kappaB inhibitor, exhibited normal morphology, global gene expression, and insulin responses.
180	11978627	However, absence of NF-kappaB activation abolished suppression of >98% of the genes normally suppressed by TNF-alpha and induction of 60-70% of the genes normally induced by TNF-alpha.
181	11978627	Moreover, extensive cell death occurred in IkappaBalpha-DN-expressing adipocytes after 2 h of TNF-alpha treatment.
182	11978627	Thus the changes in adipocyte gene expression induced by TNF-alpha could lead to insulin resistance.
183	11978627	Further, NF-kappaB is an obligatory mediator of most of these TNF-alpha responses.
184	12055342	PPAR(gamma) and glucose homeostasis.
185	12055342	Research on PPARgamma is oriented towards understanding its role in insulin sensitization, which was inspired by the discovery that antidiabetic agents, the thiazolidinediones, were agonists for PPARgamma.
186	12055342	PPARgamma stimulation improves glucose tolerance and insulin sensitivity in type 2 diabetic patients and in animal models of insulin resistance through mechanisms that are incompletely understood.
187	12055342	Upon activation, PPARgamma heterodimerizes with retinoid X receptor, recruits specific cofactors, and binds to responsive DNA elements, thereby stimulating the transcription of target genes.
188	12055342	Because PPARgamma is highly enriched in adipose tissue and because of its major role in adipocyte differentiation, it is thought that the effects of PPARgamma in adipose tissue are crucial to explain its role in insulin sensitization, but recent studies have highlighted the contribution of other tissues as well.
189	12055342	Although relatively potent for their insulin-sensitizing action, currently marketed PPARgamma activators have some important undesirable side effects.
190	12055342	Data from human genetic studies and from PPARgamma heterozygous knockout mice indicate that a reduction in PPARgamma activity could paradoxically improve insulin sensitivity.
191	12055342	These findings suggest that modulation of PPARgamma activity by partial agonists or compounds that affect cofactor recruitment might hold promise for the treatment of insulin resistance.
192	12079620	The peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor isoforms, including PPARgamma, PPARalpha, and PPARdelta, encoded by different genes.
193	12079620	PPARs bind as heterodimers with a retinoid X receptor and, upon binding agonist, interact with cofactors increasing the rate of transcription initiation.
194	12145331	Retinoid X receptor dominates the nuclear import and export of the unliganded vitamin D receptor.
195	12230428	Overexpression of the c-Myc transcription factor in liver induces glucose uptake and utilization.
196	12230428	These findings were correlated with decreased expression of genes encoding the transcription factors hepatocyte nuclear factor 3gamma, peroxisome proliferator-activated receptor alpha and retinoid X receptor.
197	12351428	Because of its pivotal role for the regulation of HDL plasma levels, we investigated in vivo and in vitro regulation of the ATP-binding cassette transporter A1 (ABCA1) by insulin and metabolites accumulating in diabetes.
198	12351428	Incubation of cultivated HepG2 hepatocytes and RAW264.7 macrophages with unsaturated fatty acids or acetoacetate, but not with insulin, glucose, saturated fatty acids, or hydroxybutyrate, downregulated ABCA1 mRNA and protein.
199	12351428	The suppressive effect of unsaturated fatty acids and acetoacetate became most obvious in cells stimulated with oxysterols or retinoic acid but was independent of the expression of the thereby regulated transcription factors liver-X-receptor alpha (LXRalpha) and retinoid-X-receptor alpha (RXRalpha), respectively.
200	12440979	Three PPAR subtypes, PPARalpha, PPARdelta (PPARbeta) and PPARgamma, have been described in mammals.
201	12440979	The tissue distribution of PPARs is heterogeneous: PPARalpha is highly expressed in liver and skeletal muscle, PPARgamma is preferentially expressed in adipose tissues, and PPARdelta is expressed in most cell types with relative abundance.
202	12440979	PPARs are transcriptionally active as heterodimeric complexes with the retinoid X receptor and bind to specific recognition sequences in the regulatory region of target genes.
203	12440979	Using these genetic and pharmacological approaches, it has been shown that PPARalpha predominantly regulates pathways of fatty acid oxidation, whereas PPARgamma modifies fatty acid synthesis and storage in adipose tissues.
204	12471115	Peroxisome proliferator-activated receptor gamma-mediated NF-kappa B activation and apoptosis in pre-B cells.
205	12471115	The role of peroxisome proliferator-activated receptor gamma (PPARgamma) in adipocyte physiology has been exploited for the treatment of diabetes.
206	12471115	A role for PPARgamma and its dimerization partner, retinoid X receptor (RXR)alpha, in death signaling was supported by 1) the expression of RXRalpha mRNA and cytosolic PPARgamma protein, 2) agonist-induced binding of PPARgamma to a PPRE, and 3) synergistic increases in apoptosis following cotreatment with PPARgamma agonists and 9-cis-retinoic acid, an RXRalpha agonist.
207	12471115	PPARgamma agonists activated NF-kappaB (p50, Rel A, c-Rel) binding to the upstream kappaB regulatory element site of c-myc.
208	12471115	Cotreatment with 9-cis-retinoic acid and PPARgamma agonists decreased the dose required to activate NF-kappaB.
209	12478728	Retinoid X receptor (RXR) modulators are being evaluated as a means for the treatment of non-insulin dependent (type II) diabetes mellitus, and substantial progress has been made in the preclinical evaluation of these compounds.
210	12481554	Vitamin D receptor and retinoid X receptor interactions in motion.
211	12481554	Vitamin D receptor (VDR) and retinoid X receptor (RXR) are members of the nuclear receptor superfamily and they bind target DNA sequences as heterodimers to regulate transcription.
212	12481554	Vitamin D receptor and retinoid X receptor interactions in motion.
213	12481554	Vitamin D receptor (VDR) and retinoid X receptor (RXR) are members of the nuclear receptor superfamily and they bind target DNA sequences as heterodimers to regulate transcription.
214	12562779	Protein fragments harboring the LXXLL motifs of the coactivators GRIP1 and SRC1 or TRAP220 interacted predominantly with the TR.retinoid X receptor heterodimeric pair in a ligand-dependent fashion.
215	12777391	Peroxisome proliferator-activated receptor-gamma represses GLUT4 promoter activity in primary adipocytes, and rosiglitazone alleviates this effect.
216	12777391	The synthetic thiazolidinedione ligands of peroxisome proliferator-activated receptor-gamma (PPARgamma) improve insulin sensitivity in type II diabetes and induce GLUT4 mRNA expression in fat and muscle.
217	12777391	We studied the regulatory effects of PPARgamma and its ligands on GLUT4 gene expression in primary rat adipocytes and CHO-K1 cells cotransfected with PPARgamma and the GLUT4 promoter reporter.
218	12777391	The -66/+163 bp GLUT4 promoter region was sufficient to mediate PPARgamma inhibitory effects.
219	12777391	The PPARgamma/retinoid X receptor-alpha heterodimer directly bound to this region, whereas binding was abolished in the presence of Rg.
220	12777391	Thus, we show that PPARgamma represses transcriptional activity of the GLUT4 promoter via direct and specific binding of PPARgamma/retinoid X receptor-alpha to the GLUT4 promoter.
221	12777391	These data suggest a novel mechanism by which Rg exerts its antidiabetic effects via detaching PPARgamma from the GLUT4 gene promoter, thus leading to increased GLUT4 expression and enhanced insulin sensitivity.
222	12777391	Peroxisome proliferator-activated receptor-gamma represses GLUT4 promoter activity in primary adipocytes, and rosiglitazone alleviates this effect.
223	12777391	The synthetic thiazolidinedione ligands of peroxisome proliferator-activated receptor-gamma (PPARgamma) improve insulin sensitivity in type II diabetes and induce GLUT4 mRNA expression in fat and muscle.
224	12777391	We studied the regulatory effects of PPARgamma and its ligands on GLUT4 gene expression in primary rat adipocytes and CHO-K1 cells cotransfected with PPARgamma and the GLUT4 promoter reporter.
225	12777391	The -66/+163 bp GLUT4 promoter region was sufficient to mediate PPARgamma inhibitory effects.
226	12777391	The PPARgamma/retinoid X receptor-alpha heterodimer directly bound to this region, whereas binding was abolished in the presence of Rg.
227	12777391	Thus, we show that PPARgamma represses transcriptional activity of the GLUT4 promoter via direct and specific binding of PPARgamma/retinoid X receptor-alpha to the GLUT4 promoter.
228	12777391	These data suggest a novel mechanism by which Rg exerts its antidiabetic effects via detaching PPARgamma from the GLUT4 gene promoter, thus leading to increased GLUT4 expression and enhanced insulin sensitivity.
229	12829629	Thiazolidinediones, peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists, have been shown to increase plasma adiponectin levels by the transcriptional induction in adipose tissues.
230	12829629	In this study, we have identified a functional PPAR-responsive element (PPRE) in human adiponectin promoter.
231	12829629	PPAR-gamma/retinoid X receptor (RXR) heterodimer directly bound to the PPRE and increased the promoter activity in cells.
232	12829629	We have also identified a responsive element of another orphan nuclear receptor, liver receptor homolog-1 (LRH-1), in adiponectin promoter.
233	12829629	LRH-1 augmented PPAR-gamma-induced transactivation of adiponectin promoter, and point mutation of the LRH-RE significantly decreased the basal and thiazolidinedione-induced activities of adiponectin promoter.
234	12829629	Our results indicate that PPAR-gamma and LRH-1 play significant roles in the transcriptional activation of adiponectin gene via the PPRE and the LRH-RE in its promoter.
235	12890579	Peroxisome proliferator-activated receptor alpha induces rat sterol carrier protein x promoter activity through two peroxisome proliferator-response elements.
236	12890579	To examine peroxisomal-proliferator-activated receptor alpha (PPARalpha) effects on this gene, 935 bp of the SCPx promoter containing both PPRE motifs was cloned in front of the chloramphenicol acetyl-transferase gene or the luciferase gene and co-transfected into HTB-9 cells with vectors that encoded for PPARalpha and retinoid X receptor (RXR).
237	12890579	The results indicate that PPARalpha was able to induce SCPx promoter activity in both cases, an effect that was enhanced by RXR and clofibrate.
238	12890579	In addition, mutational analysis studies demonstrated that both PPREs contributed to the PPARalpha/RXRalpha-dependent activation of the SCPx promoter.
239	12890579	This investigation indicates that similar to other genes involved in beta-oxidation, SCPx transcription may be controlled by fatty acid levels via PPARalpha.
240	14527633	Specifically, hyperinsulinemia elevates serum concentrations of free insulin-like growth factor-1 (IGF-1) and androgens, while simultaneously reducing insulin-like growth factor-binding protein 3 (IGFBP-3) and sex hormone-binding globulin (SHBG).
241	14527633	Since IGFBP-3 is a ligand for the nuclear retinoid X receptor alpha, insulin-mediated reductions in IGFBP-3 may also influence transcription of anti-proliferative genes normally activated by the body's endogenous retinoids.
242	14529153	Among NRs, retinoid X receptor alpha (RXRalpha)-peroxisome proliferator-activated receptor gamma (PPARgamma) heterodimers can mediate adipocyte differentiation and obesity which has been demonstrated with in vitro cell culture systems and RXR- and PPARgamma-specific ligand studies.
243	14631893	The effects of vitamin D are mediated by the nuclear vitamin D receptor, which heterodimerizes with the retinoid X receptor and changes gene transcription.
244	14670614	Peroxisome proliferator-activated receptors (PPARs) and associated transcription factors in colon cancer: reduced expression of PPARgamma-coactivator 1 (PGC-1).
245	14670614	To better understand their role, we studied the expression levels of all PPAR-isoforms and transcriptional partners such as the retinoid X receptor alpha (RXRalpha) and PPARgamma-coactivator-1 (PGC-1) by means of real-time PCR in 17 patients with colon cancer.
246	14670614	While a heterogeneous pattern was observed for the expression level of the PPAR-isoforms alpha,beta/delta and gamma, the coactivator PGC-1 was significantly decreased in 15 of 17 tumors.
247	14670614	Taken together our data suggest that the transcriptional activity of PPARgamma may not only be decreased by mutation but also by downregulation of the coactivator PGC-1 of PPARgamma.
248	14715861	Clinical and in vitro studies suggest that some patients with advanced thyroid cancer may respond to therapy with retinoic acid. mRNA expression of the six retinoic acid (RAR) and retinoid X receptor (RXR) isoforms (RARalpha, -beta, -gamma and RXRalpha, -beta, -gamma) was measured in four human thyroid cell lines, and protein expression was subsequently measured in 10 thyroid cancer cell lines.
249	14715861	Two isoforms, RARbeta and RXRgamma, were differentially expressed in the four cell lines.
250	14715861	Comparison of 10 thyroid tumors and matched normal thyroid tissue confirmed differential tumor expression of RARbeta and RXRgamma and lack of the RXRgamma isoform in normal thyroid tissue.
251	14715861	Cell lines expressing both RARbeta and RXRgamma demonstrated significant growth suppression when treated with retinoids, whereas cell lines lacking these isoforms were unaffected.
252	14715861	In summary, we identified the RARbeta and RXRgamma isoform to be differentially expressed in thyroid cancer cell lines and tumor tissue.
253	14739078	In rodent adipocyte transcription of the PEPCK-C gene is induced by thiazolidinediones (TZDs) through an element, named PCK2, in its promoter.
254	14739078	PCK2 binds a peroxisome proliferator activated receptor gamma (PPARgamma), retinoid X receptor alpha (RXRalpha) heterodimer.
255	14739078	Using gel shift experiments, we show that this effect is likely to involve the human PCK2 (hPCK2) element, which binds a protein complex that contains PPARgamma and RXRalpha.
256	14739078	We analyzed hPCK2 (position -1031 to -1015 base pairs) and nearby sequences in the PEPCK-C promoter in 403 subjects with type 2 diabetes and 123 non-diabetic controls.
257	14739078	In rodent adipocyte transcription of the PEPCK-C gene is induced by thiazolidinediones (TZDs) through an element, named PCK2, in its promoter.
258	14739078	PCK2 binds a peroxisome proliferator activated receptor gamma (PPARgamma), retinoid X receptor alpha (RXRalpha) heterodimer.
259	14739078	Using gel shift experiments, we show that this effect is likely to involve the human PCK2 (hPCK2) element, which binds a protein complex that contains PPARgamma and RXRalpha.
260	14739078	We analyzed hPCK2 (position -1031 to -1015 base pairs) and nearby sequences in the PEPCK-C promoter in 403 subjects with type 2 diabetes and 123 non-diabetic controls.
261	14749268	Liver glucokinase can be activated by peroxisome proliferator-activated receptor-gamma.
262	14749268	Thiazolidinediones (TZDs), synthetic ligands of peroxisome proliferator-activated receptor (PPAR)-gamma, are known to decrease hepatic glucose production and increase glycogen synthesis in diabetic animals.
263	14749268	The PPAR-gamma/retinoid X receptor-alpha heterodimer was bound to the element and activated the LGK promoter.
264	14967823	LXR-mediated activation of macrophage stearoyl-CoA desaturase generates unsaturated fatty acids that destabilize ABCA1.
265	14967823	ATP binding cassette transporter A1 (ABCA1) mediates the transport of cholesterol and phospholipids from cells to HDL apolipoproteins and thus modulates HDL levels and atherogenesis.
266	14967823	Because fatty acids are increased in diabetes, we examined their effects on ABCA1 activity in cultured macrophages. cAMP analogs and ligands for the liver X receptor/retinoid X receptor (LXR/RXR) system can induce Abca1 transcription in murine macrophages.
267	14967823	When induced by cAMP, unsaturated but not saturated long-chain fatty acids inhibit apolipoprotein-mediated lipid efflux by destabilizing ABCA1 protein.
268	14967823	The SCD inhibitors conjugated linoleic acid and troglitazone nearly abolished ABCA1 destabilization by palmitate and stearate but not by linoleate.
269	14967823	These results suggest that LXR/RXR ligands generate ABCA1-destabilizing monounsaturated fatty acids from their saturated precursors by activating SCD.
270	15032732	All-trans retinoic acid is known to inhibit adipocyte differentiation, whereas, molecules activating the retinoid X-receptor (rexinoids) promote the differentiation of adipocytes.
271	15299082	Among the transcript changes identified in endometrial cancer were up-regulation of the nuclear hormone receptors peroxisome proliferator-activated receptors (PPAR) alpha and gamma, whereas retinoid X receptor beta was down-regulated.
272	15299082	These results support further investigation of members of the PPAR/retinoid X receptor pathway as novel therapeutic targets in endometrial cancer.
273	15299084	Retinoid X receptor-gamma and peroxisome proliferator-activated receptor-gamma expression predicts thyroid carcinoma cell response to retinoid and thiazolidinedione treatment.
274	15299084	Nuclear hormone receptors peroxisome proliferator-activated receptor gamma (PPARgamma) and retinoid X receptor (RXR) are variably expressed in thyroid carcinoma cell lines.
275	15299084	We studied three thyroid carcinoma cell lines: BHP 5-16 (PPARgamma-/RXRgamma+), BHP 2-7 (PPARgamma+/-/RXRgamma-), and DRO-90 (RXRgamma+/PPARgamma+).
276	15299084	DRO-90 (RXRgamma+ and PPARgamma+) cells had 36 +/- 10%, 15 +/- 3%, and 13 +/- 4% growth when treated with rexinoid, thiazolidinedione, or a combination, respectively.
277	15299084	Additionally, expression of both RXRgamma and PPARgamma may be necessary for maximal growth inhibition by ligands and may be required for the increased apoptosis.
278	15320743	Pleiotropic actions of PPAR gamma activators thiazolidinediones in cardiovascular diseases.
279	15320743	Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily and form heterodimers with retinoid X receptor.
280	15320743	Although PPAR gamma is expressed predominantly in adipose tissue and associated with adipocyte differentiation and glucose homeostasis, it has been recently demonstrated that PPAR gamma is present in a variety of cell types.
281	15320743	Synthetic antidiabetic thiazolidinediones (TZDs) and natural prostaglandin D(2) (PGD(2)) metabolite, 15-deoxy-Delta(12, 14)-prostaglandin J(2) (15d-PGJ(2)), are well-known as ligands for PPAR gamma.
282	15320743	After it has been reported that activation of PPAR gamma suppresses production of proinflammatory cytokines in activated macrophages, medical interest in PPAR gamma have grown and a huge research effort has been concentrated.
283	15320743	PPAR gamma, is currently known to be implicated in various human chronic diseases such as diabetes mellitus, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, and Alzheimer's disease.
284	15320743	Moreover, PPAR gamma ligands have potent tumor modulatory effects against colorectal, prostate, and breast cancers.
285	15320743	Although activation of PPAR gamma seems to have beneficial effects on atherosclerosis and heart failure, the mechanisms by which PPAR gamma ligands prevent the development of cardiovascular diseases are not fully understood.
286	15320743	This review will focus on the latest developments in the PPAR gamma field and the roles of PPAR gamma-dependent pathway in cardiovascular diseases.
287	15383226	The inhibitory effect of 9-cis-RA was synergistically enhanced by the addition of rosiglitazone, a synthetic ligand for peroxisome proliferator-activated receptor (PPAR) gamma. 9-cis-RA also leads to adipogenesis in a dose-dependent manner.
288	15383226	In conclusion, all-trans-RA does not alter adipogenesis and glucose uptake but does inhibit leptin secretion. 9-cis-RA, however, seems to increase both adipogenesis and glucose uptake through activation of the retinoid X receptor/PPARgamma heterodimer.
289	15528275	Insulin-induced gene-1 (Insig-1) and its homolog Insig-2 encode closely related proteins of the endoplasmic reticulum that block proteolytic activation of sterol regulatory element binding proteins, membrane-bound transcription factors that activate synthesis of cholesterol and fatty acids in animal cells.
290	15528275	Herein, we identified a novel 1alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] response element in the promoter region of Insig-2 gene, which specifically binds to the heterodimer of retinoid X receptor and vitamin D receptor (VDR) and directs VDR-mediated transcriptional activation in a 1,25-(OH)2D3-dependent manner.
291	15528275	Interestingly, 1,25-(OH)2D3 is known to directly suppress the expression of peroxisome proliferator-activated receptor gamma2 protein and inhibits adipocyte differentiation of 3T3-L1 preadipocytes and murine bone marrow stromal cells.
292	15555528	DHA activates a number of nuclear hormone receptors that operate as transcription factors for molecules that modulate reduction-oxidation-sensitive and proinflammatory genes; these include the peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and the retinoid X receptor.
293	15555528	In the case of PPAR-alpha, this action is thought to prevent endothelial cell dysfunction and vascular remodeling through inhibition of: vascular smooth muscle cell proliferation, inducible nitric oxide synthase production, interleukin-1 induced cyclooxygenase (COX)-2 production, and thrombin-induced endothelin 1 production.
294	15555528	EPA depresses vascular endothelial growth factor (VEGF)-specific tyrosine kinase receptor activation and expression.
295	15555528	The mechanism of VEGF receptor down-regulation is believed to occur at the tyrosine kinase nuclear factor-kappa B (NFkappaB).
296	15555528	NFkappaB is a nuclear transcription factor that up-regulates COX-2 expression, intracellular adhesion molecule, thrombin, and nitric oxide synthase.
297	15585637	In a reporter assay with COS-7 cells, transfected with a 1alpha,25-dihydroxyvitamin D(3)-24-hydroxylase (24-OHase)-construct and VDR-expression vector, 25-OH-D(3)-3-BE induced 24-OHase promoter activity.
298	15585637	In a "pull down assay" with PC-3 cells, 25-OH-D(3)-3-BE induced strong interaction between VDR and general transcription factors, retinoid X receptor, and GRIP-1.
299	15590756	The increase in NPR-A expression was associated with an increase in NPR-A gene promoter activity that was critically dependent on the presence of a functional VD receptor response element located approximately 495 bp upstream from the transcription start site of the gene.
300	15590756	This element was associated with the VD receptor/retinoid X receptor complex in vitro.
301	15721857	PPAR-gamma regulates gene expression by forming a heterodimer with the retinoid X receptor (RXR) before binding to sequence-specific PPAR response elements (PPREs) in the promoter region of target genes, thereby regulating several metabolic pathways, including lipid biosynthesis and glucose metabolism.
302	15721857	Thiazolidinediones (TZDs, i.e. rosiglitazone, pioglitazone), which are synthetic PPAR-gamma agonists, act as insulin sensitizers and are used in the treatment of type 2 diabetes.
303	15721857	In the last few years, it has, however, become evident that the therapeutic effects of PPAR-gamma ligands reach far beyond their use as insulin sensitizers.
304	15834303	PPARgamma forms a heterodimer with the retinoid X receptor and upon ligand-activation binds to the PPAR response element in the promoter of genes to allow transcription.
305	15834303	The class of insulin-sensitizing drugs known as thiazolidinediones have been identified as specific PPARgamma agonists that have allowed the characterization of many genes regulated by PPARgamma.
306	15837528	We have shown previously that the liganded vitamin D receptor (VDR) inhibits hypertrophy and expression of hypertrophy-sensitive genes (i.e. those encoding atrial natriuretic peptide [ANP], brain natriuretic peptide and alpha skeletal actin) in neonatal cardiac myocytes.
307	15837528	In the present study we confirm a time-, ligand- and retinoid X receptor-dependent, VDR-mediated suppression of human ANP gene promoter activity.
308	15837528	Conventional deletion analysis demonstrated that the promoter region positioned between -217 and -104 is required for the VDR-dependent suppression of the hANP promoter.
309	15877285	A retinoid X receptor antagonist, HX531, improves leptin resistance without increasing plasma leptin level in KK-Ay mice under normal dietary conditions.
310	15886523	In the present study, we show that the expression of type 2 glucose transporter isoform (GLUT2) could be regulated by PPAR-gamma in the liver.
311	15886523	Rosiglitazone, PPAR-gamma agonist, activated the GLUT2 mRNA level in the primary cultured hepatocytes and Alexander cells, when these cells were transfected with PPAR-gamma/RXR-alpha.
312	15886523	Chromatin immunoprecipitation assay using ob/ob mice also showed that PPAR-gamma rather than PPAR-alpha binds to the -197/-184 region of GLUT2 promoter.
313	15886523	Taken together, liver GLUT2 may be a direct target of PPAR-gamma ligand contributing to glucose transport into liver in a condition when PAPR-gamma expression is increased as in type 2 diabetes or in severe obesity.
314	15997096	Retinoid X receptor (RXR) forms heterodimers with peroxisome proliferator-activated receptors (PPARs, with subtypes of alpha, delta and gamma), and the heterodimers can be activated by either an RXR or a PPAR subtype-specific ligand.
315	15997096	Furthermore, RT-PCR results showed that CS018 induced the expression of the PPARgamma target genes, CD36 and lipoprotein lipase (LPL).
316	16105480	Thiazolidinediones (TZDs), which are synthetic ligands for peroxisome proliferator activated receptor g (PPARg) activation, have been introduced in clinical medicine to improve insulin resistance and glycemic control in patients with type 2 diabetes.
317	16105480	The metabolic effects of TZDs are mediated by receptor-dependent activation of the PPARg-retinoid X receptor (RXR) complex and subsequent transcriptional activation of target genes.
318	16179348	Agonists for the nuclear receptor peroxisomal proliferator-activated receptor-gamma (PPARgamma) and its heterodimeric partner, retinoid X receptor (RXR), are effective agents for the treatment of type 2 diabetes.
319	16179348	Troglitazone increased skeletal muscle Irs-1 and phospho-Akt levels following in vivo insulin treatment, whereas AGN194204 increased hepatic Irs-2 and insulin stimulated phospho-Akt in liver.
320	16179348	Gene profiles of AGN194204-treated mouse liver analyzed by Ingenuity Pathway Analysis identified increases in fatty acid synthetic genes, including Srebp-1 and fatty acid synthase, a pathway previously shown to be induced by RXR agonists.
321	16179348	A network of down-regulated genes containing Foxa2, Foxa3, and G-protein subunits was identified, and decreases in these mRNA levels were confirmed by quantitative reverse transcription-PCR.
322	16179348	These studies demonstrate distinct molecular events lead to insulin sensitization by high affinity RXR and PPARgamma agonists.
323	16269450	Specific retinoid X receptor (RXR) agonists, such as LG100268 (LG268), and the thiazolidinedione (TZD) PPARgamma agonists, such as rosiglitazone, produce insulin sensitization in rodent models of insulin resistance and type 2 diabetes.
324	16513826	Thiazolidinediones and rexinoids induce peroxisome proliferator-activated receptor-coactivator (PGC)-1alpha gene transcription: an autoregulatory loop controls PGC-1alpha expression in adipocytes via peroxisome proliferator-activated receptor-gamma coactivation.
325	16513826	They are activators of peroxisome proliferator-activated receptor (PPAR)-gamma, and adipose tissue constitutes a major site for their biological effects.
326	16513826	PPAR coactivator (PGC)-1alpha is a transcriptional coactivator of PPARgamma and other transcription factors.
327	16513826	Here we report that PGC-1alpha gene expression in brown and white adipocytes is a direct target of TZDs via PPARgamma activation.
328	16513826	Activators of the retinoid X receptor also induce PGC-1alpha gene expression.
329	16513826	This is due to the presence of a PPARgamma-responsive element in the distal region of the PGC-1alpha gene promoter that binds PPARgamma/retinoid X receptor heterodimers.
330	16513826	Moreover, there is a positive autoregulatory loop of control of the PGC-1alpha gene through coactivation of PPARgamma responsiveness to TZDs by PGC-1alpha itself.
331	16513826	Thiazolidinediones and rexinoids induce peroxisome proliferator-activated receptor-coactivator (PGC)-1alpha gene transcription: an autoregulatory loop controls PGC-1alpha expression in adipocytes via peroxisome proliferator-activated receptor-gamma coactivation.
332	16513826	They are activators of peroxisome proliferator-activated receptor (PPAR)-gamma, and adipose tissue constitutes a major site for their biological effects.
333	16513826	PPAR coactivator (PGC)-1alpha is a transcriptional coactivator of PPARgamma and other transcription factors.
334	16513826	Here we report that PGC-1alpha gene expression in brown and white adipocytes is a direct target of TZDs via PPARgamma activation.
335	16513826	Activators of the retinoid X receptor also induce PGC-1alpha gene expression.
336	16513826	This is due to the presence of a PPARgamma-responsive element in the distal region of the PGC-1alpha gene promoter that binds PPARgamma/retinoid X receptor heterodimers.
337	16513826	Moreover, there is a positive autoregulatory loop of control of the PGC-1alpha gene through coactivation of PPARgamma responsiveness to TZDs by PGC-1alpha itself.
338	16713393	The mechanisms underlying these effects are not well-established, but may involve TFA incorporation into endothelial cell, monocyte/macrophage, or adipocyte cell membranes (affecting membrane signaling pathway relating to inflammation) or ligand-dependent effects on peroxisome proliferator-activated receptor (PPAR) or retinoid X receptor (RXR) pathways.
339	16782410	PPARs heterodimerize with the retinoid X receptor (RXR) and then act as transcription factors to modulate the function of many target genes.
340	16782410	Activators of PPARalpha (fibrates) and PPARgamma (thiazolidinediones or glitazones) antagonize angiotensin II effects in vivo and in vitro and have cardiovascular antioxidant and anti-inflammatory actions.
341	17045164	Peroxisome proliferator activated-receptor gamma (PPARgamma) binds to peroxisome receptor response elements with its heterodimeric partner, retinoid X receptor, and regulates downstream gene expression.
342	17071612	Clinically apparent hereditary vitamin D-resistant rickets (HVDRR) usually results from a loss of function mutation in the vitamin D receptor (VDR).
343	17071612	Hormone resistance resulted from constitutive overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) that competed with a normally functioning VDR-retinoid X receptor (RXR) dimer for binding to the vitamin D response element (VDRE).
344	17071612	By contrast, transient expression of an hnRNP C1/C2 small interfering RNA increased VDR transactivation by 39% (p < 0.005).
345	17071612	Chromatin immunoprecipitation of nucleoproteins bound to the transcriptionally active 1,25-dihydroxy vitamin D-driven CYP24 promoter revealed the presence of REBiP in vitamin D-responsive human cells and indicated that the normal pattern of 1,25-dihydroxy vitamin D-initiated cyclical movement of the VDR on and off the VDRE is legislated by competitive, reciprocal occupancy of the VDRE by hnRNP C1/C2.
346	17071612	The temporal and reciprocal pattern of VDR and hnRNPC1/C2 interaction with the VDRE was lost in HVDRR cells overexpressing the hnRNP C1/C2 REBiP.
347	17148746	The three peroxisome-proliferator-activated receptor (PPAR) subtypes PPAR-alpha, PPAR-gamma, and PPAR-delta are ligand-activated transcription factors of the nuclear receptor family.
348	17148746	PPARs form obligate heterodimers with the retinoid X receptor, which bind to peroxisome-proliferator-response elements (PPREs).
349	17148746	PPAR-alpha is expressed mainly in liver, brown fat, kidney, heart, and skeletal muscle; PPAR-gamma in intestine and adipose tissue; PPAR-alpha and PPAR-gamma are both expressed in vascular endothelium, smooth muscle cells, macrophages, and foam cells; PPAR-delta in skeletal muscle, human embryonic kidney, intestine, heart, adipose tissue, developing brain, and keratinocytes.
350	17148746	Agonists of PPAR-alpha and PPAR-gamma are currently used to treat diabetic dyslipidemia and type 2 diabetes.
351	17512303	Studies on the association of fatty acid-binding protein 2 (FABP2) A54T and promoter polymorphism, and type 2 diabetes mellitus, insulin, and triglyceride levels are controversial.
352	17512303	When calculated independently from promoter variability, postprandial triglyceride levels were significantly higher and postprandial insulin sensitivity (homeostasis model assessment index) was lower in homozygous carriers of FABP2 T54T compared with carriers of the FABP2 exon wild-type allele (FABP2 A54A and A54T).
353	17512303	Reporter gene assays indicated a higher responsiveness to peroxisome proliferator-activating receptor-gamma (PPAR-gamma)/retinoid X receptor (RXR) of FABP2 promoter B vs promoter A.
354	17932108	We investigated the effect of the HIV-1 accessory protein viral protein R (Vpr) on the activity of the peroxisome proliferator-activating receptor-gamma (PPARgamma), a key regulator of adipocyte differentiation and tissue insulin sensitivity.
355	17932108	We investigated Vpr interaction with the PPAR/retinoid X receptor (RXR)-binding site of the c-Cbl-associating protein (CAP) gene using the chromatin immunoprecipitation assay as well as the interaction of Vpr and PPARgamma using coimmunoprecipitation.
356	17932108	Vpr suppressed mRNA expression of PPARgamma-responsive genes in undifferentiated 3T3-L1 cells and associated with the PPAR/RXR-binding site located in the promoter region of the CAP gene.
357	17932108	Vpr delivered either by an expression plasmid or as protein added to media suppressed PPARgamma agonist-induced adipocyte differentiation, assessed as lipid accumulation and mRNA expression of the adipocyte differentiation marker adipocyte P2 in 3T3-L1 cells.
358	17970749	Peroxisome proliferator-activated receptor alpha-retinoid X receptor agonists induce beta-cell protection against palmitate toxicity.
359	17970749	A combination of PPARalpha and retinoid X receptor (RXR) agonists acted synergistically and led to complete protection; this was associated with enhanced expression levels of genes involved in mitochondrial and peroxisomal beta-oxidation, lipid metabolism, and peroxisome proliferation.
360	17970749	Peroxisome proliferator-activated receptor alpha-retinoid X receptor agonists induce beta-cell protection against palmitate toxicity.
361	17970749	A combination of PPARalpha and retinoid X receptor (RXR) agonists acted synergistically and led to complete protection; this was associated with enhanced expression levels of genes involved in mitochondrial and peroxisomal beta-oxidation, lipid metabolism, and peroxisome proliferation.
362	18055466	Glucose decreased PPARalpha interaction with fatty acid metabolites and steroid receptor coactivator-1 while increasing PPARalpha interaction with DNA.
363	18055466	Concomitantly, glucose increased PPARalpha interaction with steroid receptor coactivator-1, DNA binding, and transactivation of beta-oxidation pathways in the presence of activating ligands.
364	18055466	Heterodimerization of PPARalpha to the retinoid X receptor-alpha resulted in even larger increases in transactivation with the addition of glucose.
365	18162523	Induction of apoptosis in human prostate cancer cells by insulin-like growth factor binding protein-3 does not require binding to retinoid X receptor-alpha.
366	18162523	Binding to RXR-alpha has been proposed to be required for IGFBP-3 to induce apoptosis.
367	18162523	A COOH-terminal region in IGFBP-3 (residues 215-232) contains a nuclear localization signal, and binding domains for RXR-alpha and heparin (HBD).
368	18162523	Different combinations of the 11 amino acids in this region that differ from IGFBP-1, a related IGFBP, which does not localize to the nucleus or bind RXR-alpha, were mutated to the IGFBP-1 sequence.
369	18162523	IGFBP-3 binding to glutathione S-transferase-RXR-alpha only was lost when all 11 sites were mutated (HBD-11m-IGFBP-3).
370	18162523	Expressed nuclear RXR-alpha did not transport cytoplasmic IGFBP-3 nuclear localization signal mutants that can bind RXR-alpha to the nucleus even after treatment with RXR ligand.
371	18162523	We conclude that in PC-3 cells, RXR-alpha is not required for the nuclear translocation of IGFBP-3 and that IGFBP-3 can induce apoptosis in human prostate cancer cells without binding RXR-alpha.
372	18162523	Induction of apoptosis in human prostate cancer cells by insulin-like growth factor binding protein-3 does not require binding to retinoid X receptor-alpha.
373	18162523	Binding to RXR-alpha has been proposed to be required for IGFBP-3 to induce apoptosis.
374	18162523	A COOH-terminal region in IGFBP-3 (residues 215-232) contains a nuclear localization signal, and binding domains for RXR-alpha and heparin (HBD).
375	18162523	Different combinations of the 11 amino acids in this region that differ from IGFBP-1, a related IGFBP, which does not localize to the nucleus or bind RXR-alpha, were mutated to the IGFBP-1 sequence.
376	18162523	IGFBP-3 binding to glutathione S-transferase-RXR-alpha only was lost when all 11 sites were mutated (HBD-11m-IGFBP-3).
377	18162523	Expressed nuclear RXR-alpha did not transport cytoplasmic IGFBP-3 nuclear localization signal mutants that can bind RXR-alpha to the nucleus even after treatment with RXR ligand.
378	18162523	We conclude that in PC-3 cells, RXR-alpha is not required for the nuclear translocation of IGFBP-3 and that IGFBP-3 can induce apoptosis in human prostate cancer cells without binding RXR-alpha.
379	18162523	Induction of apoptosis in human prostate cancer cells by insulin-like growth factor binding protein-3 does not require binding to retinoid X receptor-alpha.
380	18162523	Binding to RXR-alpha has been proposed to be required for IGFBP-3 to induce apoptosis.
381	18162523	A COOH-terminal region in IGFBP-3 (residues 215-232) contains a nuclear localization signal, and binding domains for RXR-alpha and heparin (HBD).
382	18162523	Different combinations of the 11 amino acids in this region that differ from IGFBP-1, a related IGFBP, which does not localize to the nucleus or bind RXR-alpha, were mutated to the IGFBP-1 sequence.
383	18162523	IGFBP-3 binding to glutathione S-transferase-RXR-alpha only was lost when all 11 sites were mutated (HBD-11m-IGFBP-3).
384	18162523	Expressed nuclear RXR-alpha did not transport cytoplasmic IGFBP-3 nuclear localization signal mutants that can bind RXR-alpha to the nucleus even after treatment with RXR ligand.
385	18162523	We conclude that in PC-3 cells, RXR-alpha is not required for the nuclear translocation of IGFBP-3 and that IGFBP-3 can induce apoptosis in human prostate cancer cells without binding RXR-alpha.
386	18162523	Induction of apoptosis in human prostate cancer cells by insulin-like growth factor binding protein-3 does not require binding to retinoid X receptor-alpha.
387	18162523	Binding to RXR-alpha has been proposed to be required for IGFBP-3 to induce apoptosis.
388	18162523	A COOH-terminal region in IGFBP-3 (residues 215-232) contains a nuclear localization signal, and binding domains for RXR-alpha and heparin (HBD).
389	18162523	Different combinations of the 11 amino acids in this region that differ from IGFBP-1, a related IGFBP, which does not localize to the nucleus or bind RXR-alpha, were mutated to the IGFBP-1 sequence.
390	18162523	IGFBP-3 binding to glutathione S-transferase-RXR-alpha only was lost when all 11 sites were mutated (HBD-11m-IGFBP-3).
391	18162523	Expressed nuclear RXR-alpha did not transport cytoplasmic IGFBP-3 nuclear localization signal mutants that can bind RXR-alpha to the nucleus even after treatment with RXR ligand.
392	18162523	We conclude that in PC-3 cells, RXR-alpha is not required for the nuclear translocation of IGFBP-3 and that IGFBP-3 can induce apoptosis in human prostate cancer cells without binding RXR-alpha.
393	18162523	Induction of apoptosis in human prostate cancer cells by insulin-like growth factor binding protein-3 does not require binding to retinoid X receptor-alpha.
394	18162523	Binding to RXR-alpha has been proposed to be required for IGFBP-3 to induce apoptosis.
395	18162523	A COOH-terminal region in IGFBP-3 (residues 215-232) contains a nuclear localization signal, and binding domains for RXR-alpha and heparin (HBD).
396	18162523	Different combinations of the 11 amino acids in this region that differ from IGFBP-1, a related IGFBP, which does not localize to the nucleus or bind RXR-alpha, were mutated to the IGFBP-1 sequence.
397	18162523	IGFBP-3 binding to glutathione S-transferase-RXR-alpha only was lost when all 11 sites were mutated (HBD-11m-IGFBP-3).
398	18162523	Expressed nuclear RXR-alpha did not transport cytoplasmic IGFBP-3 nuclear localization signal mutants that can bind RXR-alpha to the nucleus even after treatment with RXR ligand.
399	18162523	We conclude that in PC-3 cells, RXR-alpha is not required for the nuclear translocation of IGFBP-3 and that IGFBP-3 can induce apoptosis in human prostate cancer cells without binding RXR-alpha.
400	18162523	Induction of apoptosis in human prostate cancer cells by insulin-like growth factor binding protein-3 does not require binding to retinoid X receptor-alpha.
401	18162523	Binding to RXR-alpha has been proposed to be required for IGFBP-3 to induce apoptosis.
402	18162523	A COOH-terminal region in IGFBP-3 (residues 215-232) contains a nuclear localization signal, and binding domains for RXR-alpha and heparin (HBD).
403	18162523	Different combinations of the 11 amino acids in this region that differ from IGFBP-1, a related IGFBP, which does not localize to the nucleus or bind RXR-alpha, were mutated to the IGFBP-1 sequence.
404	18162523	IGFBP-3 binding to glutathione S-transferase-RXR-alpha only was lost when all 11 sites were mutated (HBD-11m-IGFBP-3).
405	18162523	Expressed nuclear RXR-alpha did not transport cytoplasmic IGFBP-3 nuclear localization signal mutants that can bind RXR-alpha to the nucleus even after treatment with RXR ligand.
406	18162523	We conclude that in PC-3 cells, RXR-alpha is not required for the nuclear translocation of IGFBP-3 and that IGFBP-3 can induce apoptosis in human prostate cancer cells without binding RXR-alpha.
407	18177744	Peroxisome proliferator-activated receptors (PPARs), sterol regulatory element binding proteins, liver X receptor alpha, retinoid X receptor alpha, farnesoid X receptor alpha, hepatic nuclear factor 4alpha and nuclear factor kappaB contribute to these nuclear actions of bioactive lipids with complex interactions.
408	18177744	In particular, the function of bioactive lipids as dietary adiponectin inducers (dietary insulin sensitizers) deserves attention with respect to alleviation of metabolic syndrome by dietary manipulation.
409	18769028	Farnesoid X receptor induces GLUT4 expression through FXR response element in the GLUT4 promoter.
410	18769028	GLUT4, the main insulin-responsive glucose transporter, plays a critical role in maintaining systemic glucose homeostasis and is subject to complicated metabolic regulation.
411	18769028	GLUT4 expression disorder might cause insulin resistance, and over-expression of GLUT4 has been confirmed to ameliorate diabetes.
412	18769028	Here, we reported that farnesoid X receptor (FXR) and its agonist chenodeoxycholic acid (CDCA) could induce GLUT4 transcription in 3T3-L1 and HepG2 cells.
413	18769028	The following progressive 5'-deletion analysis and site-mutation investigation further suggested that FXR could induce GLUT4 expression through FXR response element (FXRE) in the GLUT4 promoter.
414	18769028	EMSA and knock-down of retinoid X receptor (RXR) indicated that FXR binds to the GLUT4-FXRE as a monomer and RXR does not participate in the FXR stimulation of GLUT4 expression.
415	18769028	In addition, we demonstrated that FXR does not interfere with insulin-induced GLUT4 translocation to plasma membrane.
416	18769028	All these data thereby implied that FXR is a new transcription factor of GLUT4, further elucidating the potential role for FXR in glucose metabolism.
417	18981473	PPARgamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale.
418	18981473	Peroxisome proliferator-activated receptor gamma(PPARgamma), a nuclear receptor and the target of anti-diabetic thiazolinedione drugs, is known as the master regulator of adipocyte biology.
419	18981473	Although it regulates hundreds of adipocyte genes, PPARgamma binding to endogenous genes has rarely been demonstrated.
420	18981473	The consensus PPARgamma/RXRalpha "DR-1"-binding motif was found at most of the sites, and ChIP for RXRalpha showed colocalization at nearly all locations tested.
421	18981473	Bioinformatics analysis also revealed CCAAT/enhancer-binding protein (C/EBP)-binding motifs in the vicinity of most PPARgamma-binding sites, and genome-wide analysis of C/EBPalpha binding demonstrated that it localized to 3350 of the locations bound by PPARgamma.
422	18981473	C/EBPbeta also plays a role at many of these genes, such that both C/EBPalpha and beta are required along with PPARgamma for robust adipocyte-specific gene expression.
423	18981473	Thus, PPARgamma and C/EBP factors cooperatively orchestrate adipocyte biology by adjacent binding on an unanticipated scale.
424	18993052	Isomers 9E,11E-, 9Z,11Z-, 10E,12Z- and 11Z,13E-CLA decreased production of proinflammatory cytokines such as interleukin (IL)-1alpha, IL-1beta and IL-6.
425	18993052	Coactivator recruitment by CLA isomers showed their distinct properties as selective receptor modulators for PPARgamma and RXRalpha.
426	19118026	The peroxisome proliferator-activated receptor (PPAR) gamma is one member of the nuclear receptor superfamily that contains in excess of 80 described receptors.
427	19118026	Once activated, PPARgamma will preferentially bind with retinoid X receptor alpha and signal antiproliferative, antiangiogenic, and prodifferentiation pathways in several tissue types, thus making it a highly useful target for down-regulation of carcinogenesis.
428	19700678	Milk and fresh cream increased the activity of human retinoid X receptor (RXR)alpha as well as PPARalpha and PPARdelta, whereas neither affected vitamin D3 receptor, estrogen receptors alpha and beta, or thyroid receptors alpha and beta.
429	19700678	This study unambiguously clarified at the cellular level that cow's milk increased the activities of human PPARalpha, PPARdelta, and RXRalpha.
430	19700678	The possible role in enhancing the activities of PPARalpha, PPARdelta, and RXRalpha, and the health benefits of cow's milk were discussed.
431	19700678	Milk and fresh cream increased the activity of human retinoid X receptor (RXR)alpha as well as PPARalpha and PPARdelta, whereas neither affected vitamin D3 receptor, estrogen receptors alpha and beta, or thyroid receptors alpha and beta.
432	19700678	This study unambiguously clarified at the cellular level that cow's milk increased the activities of human PPARalpha, PPARdelta, and RXRalpha.
433	19700678	The possible role in enhancing the activities of PPARalpha, PPARdelta, and RXRalpha, and the health benefits of cow's milk were discussed.
434	19700678	Milk and fresh cream increased the activity of human retinoid X receptor (RXR)alpha as well as PPARalpha and PPARdelta, whereas neither affected vitamin D3 receptor, estrogen receptors alpha and beta, or thyroid receptors alpha and beta.
435	19700678	This study unambiguously clarified at the cellular level that cow's milk increased the activities of human PPARalpha, PPARdelta, and RXRalpha.
436	19700678	The possible role in enhancing the activities of PPARalpha, PPARdelta, and RXRalpha, and the health benefits of cow's milk were discussed.
437	20075562	Human catalase gene is regulated by peroxisome proliferator activated receptor-gamma through a response element distinct from that of mouse.
438	20075562	PPARgamma agonists not only improve insulin sensitivity but also eliminate oxidative stress.
439	20075562	In mouse, catalase, a major antioxidant enzyme, is directly regulated by PPARgamma through two PPARgamma binding elements in its promoter.
440	20075562	Expression of catalase was significantly upregulated in human primary adipocytes upon treatment with a PPARgamma agonist.
441	20075562	However, the mouse PPARgamma response elements are not functionally conserved in human catalase promoter.
442	20075562	In luciferase reporter assay containing human catalase promoter, PPARgamma /RXRalpha, in combination of a PPARgamma agonist significantly transactivated 19 kb of promoter and this was mediated via a novel PPARgamma response element (PPRE) at -12 kb from transcription initiation site of human catalase gene.
443	20075562	Together, our results indicate that PPARgamma regulates the expression of catalase gene in human through a PPRE distinct from that of mouse, and could explain, at least in part, the observed inhibitory effects of PPARgamma on oxidative stress in human.
444	20364085	This increased sensitivity correlated with increased expression of the gene encoding the ubiquitin hydrolase/ligase ubiquitin carboxyterminal esterase L1 (UCH-L1) and with increased degradation of the PPARgamma heterodimerization partner retinoid X receptor alpha (RXRalpha), but not RXRbeta, in visceral WAT from obese humans and mice.
445	20364085	Interestingly, increased UCH-L1 expression and RXRalpha proteasomal degradation was induced in vitro by conditions mimicking hypoxia, a condition that occurs in obese visceral WAT.
446	20364085	Increasing the RXRalpha/RXRbeta ratio resulted in increased PPARgamma responsiveness following agonist stimulation.
447	20364085	Thus, the selective proteasomal degradation of RXRalpha initiated by UCH-L1 upregulation modulates the relative affinity of PPARgamma heterodimers for SMRT and their responsiveness to PPARgamma agonists, ultimately activating the PPARgamma-controlled gene network in visceral WAT of obese animals and humans.
448	20364085	This increased sensitivity correlated with increased expression of the gene encoding the ubiquitin hydrolase/ligase ubiquitin carboxyterminal esterase L1 (UCH-L1) and with increased degradation of the PPARgamma heterodimerization partner retinoid X receptor alpha (RXRalpha), but not RXRbeta, in visceral WAT from obese humans and mice.
449	20364085	Interestingly, increased UCH-L1 expression and RXRalpha proteasomal degradation was induced in vitro by conditions mimicking hypoxia, a condition that occurs in obese visceral WAT.
450	20364085	Increasing the RXRalpha/RXRbeta ratio resulted in increased PPARgamma responsiveness following agonist stimulation.
451	20364085	Thus, the selective proteasomal degradation of RXRalpha initiated by UCH-L1 upregulation modulates the relative affinity of PPARgamma heterodimers for SMRT and their responsiveness to PPARgamma agonists, ultimately activating the PPARgamma-controlled gene network in visceral WAT of obese animals and humans.
452	20364085	This increased sensitivity correlated with increased expression of the gene encoding the ubiquitin hydrolase/ligase ubiquitin carboxyterminal esterase L1 (UCH-L1) and with increased degradation of the PPARgamma heterodimerization partner retinoid X receptor alpha (RXRalpha), but not RXRbeta, in visceral WAT from obese humans and mice.
453	20364085	Interestingly, increased UCH-L1 expression and RXRalpha proteasomal degradation was induced in vitro by conditions mimicking hypoxia, a condition that occurs in obese visceral WAT.
454	20364085	Increasing the RXRalpha/RXRbeta ratio resulted in increased PPARgamma responsiveness following agonist stimulation.
455	20364085	Thus, the selective proteasomal degradation of RXRalpha initiated by UCH-L1 upregulation modulates the relative affinity of PPARgamma heterodimers for SMRT and their responsiveness to PPARgamma agonists, ultimately activating the PPARgamma-controlled gene network in visceral WAT of obese animals and humans.
456	20364085	This increased sensitivity correlated with increased expression of the gene encoding the ubiquitin hydrolase/ligase ubiquitin carboxyterminal esterase L1 (UCH-L1) and with increased degradation of the PPARgamma heterodimerization partner retinoid X receptor alpha (RXRalpha), but not RXRbeta, in visceral WAT from obese humans and mice.
457	20364085	Interestingly, increased UCH-L1 expression and RXRalpha proteasomal degradation was induced in vitro by conditions mimicking hypoxia, a condition that occurs in obese visceral WAT.
458	20364085	Increasing the RXRalpha/RXRbeta ratio resulted in increased PPARgamma responsiveness following agonist stimulation.
459	20364085	Thus, the selective proteasomal degradation of RXRalpha initiated by UCH-L1 upregulation modulates the relative affinity of PPARgamma heterodimers for SMRT and their responsiveness to PPARgamma agonists, ultimately activating the PPARgamma-controlled gene network in visceral WAT of obese animals and humans.
460	20656484	The order of agonistic activity toward both PPARgamma/RXRalpha and LXRalpha/RXRalpha was the same as it was for RXR, that is, 11>10>12.
461	20660599	Overexpression via adenovirus-mediated gene transfer and siRNA-mediated gene silencing established that hepatocyte nuclear factor 4 (HNF-4) is an important regulator of apoM gene transcription in hepatic cells. apoM promoter deletion analysis combined with DNA affinity precipitation and chromatin immunoprecipitation assays revealed that HNF-4 binds to a hormone-response element (HRE) in the proximal apoM promoter (nucleotides -33 to -21).
462	20660599	Mutagenesis of this HRE decreased basal hepatic apoM promoter activity to 10% of control and abolished the HNF4-mediated transactivation of the apoM promoter.
463	20660599	In addition to HNF-4, homodimers of retinoid X receptor and heterodimers of retinoid X receptor with receptors for retinoic acid, thyroid hormone, fibrates (peroxisome proliferator-activated receptor), and oxysterols (liver X receptor) were shown to bind with different affinities to the proximal HRE in vitro and in vivo.
464	20667726	Retinoid X receptor (RXR) agonists are candidate agents for the treatment of metabolic syndrome and type 2 diabetes via activation of peroxisome proliferator-activated receptor (PPAR)/RXR or liver X receptor (LXR)/RXR-heterodimers, which control lipid and glucose metabolism.
465	20798333	Nuclear hormone retinoid X receptor (RXR) negatively regulates the glucose-stimulated insulin secretion of pancreatic ß-cells.
466	20945395	Retinoic acid receptor-mediated signaling protects cardiomyocytes from hyperglycemia induced apoptosis: role of the renin-angiotensin system.
467	20945395	Activation of the retinoic acid receptor (RAR) and retinoid X receptor (RXR) has an anti-diabetic effect; but, a role in diabetic cardiomyopathy remains unclear.
468	20945395	Using neonatal and adult cardiomyocytes, we determined the role of RAR and RXR in hyperglycemia-induced apoptosis and expression of renin-angiotensin system (RAS) components.
469	20945395	Moreover, HG induced gene expression of angiotensinogen, renin, AT(1) R, and angiotensin II (Ang II) synthesis were inhibited by RARα agonists and promoted by silencing RARα.
470	20945395	Activation of RXRα, downregulated the expression of AT(1) R; and RXRα silencing accelerated HG induced expression of angiotensinogen and Ang II synthesis, whereas there was no significant effect on renin gene expression.
471	21071580	Malfunctioning of retinoid X receptor (RXR) α due to phosphorylation by Ras/MAPK also plays a critical role in liver carcinogenesis.
472	21071580	ACR markedly inhibited the activation of Ras and phosphorylation of the ERK (extracellular signal-regulated kinase) and RXRα proteins in the livers of experimental mice.
473	21071580	It also increased the expression of RAR β and p21(CIP1) mRNA while decreasing the expression of cyclin D1, c-Fos, and c-Jun mRNA in the liver, thereby restoring RXRα function.
474	21071580	The serum levels of TNF-α and the expression levels of TNF- α, IL-6, and IL-1 β mRNA in the livers of DEN-treated db/db mice were decreased by ACR treatment, suggesting attenuation of the chronic inflammation induced by excessive fatty deposits.
475	21628978	However, we hypothesized that retinoid X receptor (RXR) agonists, which are researched for the treatment of type 2 diabetes, will also be useful like metformin, which shows insulin-sparing effect in type 1 diabetes.
476	21803771	ChIP scan of the 6-kb 5' upstream region of the mouse nephrin gene identified several putative vitamin D response elements (VDREs), and EMSA confirmed that the VDRE at -312 (a DR4-type VDRE) could be bound by vitamin D receptor (VDR)/retinoid X receptor.
477	21803771	ChIP assays showed that, upon 1,25(OH)(2)D(3) activation, VDR bound to this VDRE leading to recruitment of DRIP205 and RNA polymerase II and histone 4 acetylation.
478	21803771	Treatment of mice with a vitamin D analog induced nephrin mRNA and protein in the kidney, accompanied by increased VDR binding to the -312VDRE and histone 4 acetylation. 1,25(OH)(2)D(3) reversed high glucose-induced nephrin reduction in podocytes, and vitamin D analogs prevented nephrin decline in both type 1 and 2 diabetic mice.
479	22023374	Application of back propagation artificial neural network on genetic variants in adiponectin ADIPOQ, peroxisome proliferator-activated receptor-γ, and retinoid X receptor-α genes and type 2 diabetes risk in a Chinese Han population.
480	22292422	VA activities are mediated by the metabolite of retinol catabolism, retinoic acid, which activates the retinoic acid receptor and retinoid X receptor (RXR).
481	22384078	(+)-Rutamarin as a dual inducer of both GLUT4 translocation and expression efficiently ameliorates glucose homeostasis in insulin-resistant mice.
482	22384078	Glucose transporter 4 (GLUT4) is a principal glucose transporter in response to insulin, and impaired translocation or decreased expression of GLUT4 is believed to be one of the major pathological features of type 2 diabetes mellitus (T2DM).
483	22384078	Here we report that the natural product (+)-Rutamarin (Rut) functions as an efficient dual inducer on both insulin-induced GLUT4 translocation and expression.
484	22384078	Subsequent investigation of Rut acting targets indicates that as a specific protein tyrosine phosphatase 1B (PTP1B) inhibitor Rut induces basal GLUT4 translocation to some extent and largely enhances insulin-induced GLUT4 translocation through PI3 kinase-AKT/PKB pathway, while as an agonist of retinoid X receptor α (RXRα), Rut potently increases GLUT4 expression.
485	22466572	Retinoid X receptor (RXR) agonists are reported to exhibit blood glucose-lowering action owing to peroxisome proliferator-activated receptor (PPAR)/RXR or liver X receptor (LXR)/RXR activation, but may also cause adverse effects such as blood triglyceride elevation.
486	22489042	Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear hormone receptors that control the expression of genes involved in a variety of physiologic processes, through heterodimerization with retinoid X receptor and complex formation with various cofactors.
487	22782502	When occupied by 1,25D, VDR interacts with the retinoid X receptor (RXR) to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1,25D.
488	22782502	For example, 1,25D induces RANKL, SPP1 (osteopontin), and BGP (osteocalcin) to govern bone mineral remodeling; TRPV6, CaBP(9k), and claudin 2 to promote intestinal calcium absorption; and TRPV5, klotho, and Npt2c to regulate renal calcium and phosphate reabsorption.
489	22782502	VDR appears to function unliganded by 1,25D in keratinocytes to drive mammalian hair cycling via regulation of genes such as CASP14, S100A8, SOSTDC1, and others affecting Wnt signaling.
490	23395853	Retinoids, through activation of retinoic acid receptor (RAR) and retinoid x receptor (RXR), have been linked to control glucose and lipid homeostasis, with effects on obesity and diabetes.
491	23395853	Diabetic cardiomyopathy was characterized in ZDF rats by increased oxidative stress, apoptosis, fibrosis, inflammation, activation of MAP kinases and NF-κB signaling and diminished Akt phosphorylation, along with decreased glucose transport and increased cardiac lipid accumulation, and ultimately diastolic dysfunction.
492	23395853	Am580 and LGD1069 attenuated diabetes-induced cardiac dysfunction and the pathological alterations, by improving glucose tolerance and insulin resistance; facilitating Akt activation and glucose utilization, and attenuating oxidative stress and interrelated MAP kinase and NF-κB signaling pathways.
493	23959802	Retinol-binding protein 4 and its membrane receptor STRA6 control adipogenesis by regulating cellular retinoid homeostasis and retinoic acid receptor α activity.
494	23959802	Retinoids are vitamin A (retinol) derivatives and complex regulators of adipogenesis by activating specific nuclear receptors, including the retinoic acid receptor (RAR) and retinoid X receptor (RXR).
495	23959802	Circulating retinol-binding protein 4 (RBP4) and its membrane receptor STRA6 coordinate cellular retinol uptake.
496	23959802	It is unknown whether retinol levels and the activity of RAR and RXR in adipocyte precursors are linked via RBP4/STRA6.
497	23959802	Here, we show that STRA6 is expressed in precursor cells and, dictated by the apo- and holo-RBP4 isoforms, mediates bidirectional retinol transport that controls RARα activity and subsequent adipocyte differentiation.
498	23959802	Thus, STRA6 in adipocyte precursor cells links nuclear RARα activity to the circulating RBP4 isoforms, whose ratio in obese mice was shifted toward limiting the adipogenic potential of their precursors.
499	17962386	A peroxisome proliferator-activated receptor gamma-retinoid X receptor heterodimer physically interacts with the transcriptional activator PAX6 to inhibit glucagon gene transcription.
500	17962386	However, how thiazolidinediones and PPARgamma inhibit PAX6 activity at the glucagon promoter remained unknown.
501	17962386	Like PPARgamma ligands, also retinoid X receptor (RXR) agonists inhibited glucagon gene transcription in a PPARgamma-dependent manner.
502	17962386	A peroxisome proliferator-activated receptor gamma-retinoid X receptor heterodimer physically interacts with the transcriptional activator PAX6 to inhibit glucagon gene transcription.
503	17962386	However, how thiazolidinediones and PPARgamma inhibit PAX6 activity at the glucagon promoter remained unknown.
504	17962386	Like PPARgamma ligands, also retinoid X receptor (RXR) agonists inhibited glucagon gene transcription in a PPARgamma-dependent manner.
505	19114589	Angiotensin-converting enzyme (ACE) inhibitors modulate cellular retinol-binding protein 1 and adiponectin expression in adipocytes via the ACE-dependent signaling cascade.
506	19114589	Inhibitors of the angiotensin-converting enzyme (ACE) decrease angiotensin II production and activate an intracellular signaling cascade that affects gene expression in endothelial cells.
507	19114589	In adipocytes, the overexpression of CRBP1 enhanced (4- to 5-fold) the activity of promoters containing response elements for retinol-dependent nuclear receptors [retinoic acid receptor (RAR) and retinoid X receptor (RXR)] or peroxisome proliferator-activated receptors (PPAR).
508	19114589	CRBP1 overexpression also enhanced the promoter activity (by 470 +/- 40%) and expression/release of the anti-inflammatory and antiatherogenic adipokine adiponectin (cellular adiponectin by 196 +/- 24%, soluble adiponectin by 228 +/- 74%).
509	19114589	Significantly increased adiponectin secretion was also observed after ACE inhibitor treatment of human preadipocytes, an effect prevented by small interfering RNA against CRBP1.
510	19114589	In patients with coronary artery disease or type 2 diabetes, ACE inhibition also significantly increased plasma adiponectin levels (1.6- or 2.1-fold, respectively).
511	19114589	In summary, ACE inhibitors affect adipocyte homeostasis via CRBP1 through the activation of RAR/RXR-PPAR signaling and up-regulation of adiponectin.
512	19114589	The latter may contribute to the beneficial effects of ACE inhibitors on the development of type 2 diabetes in patients with an activated renin-angiotensin system.