Ignet

Gene Information

Gene symbol: MAFA

Gene name: v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (avian)

HGNC ID: 23145

Synonyms: RIPE3b1, hMafA

Related Genes

#	Gene Symbol	Number of hits
1	ARX	1 hits
2	ATF6	1 hits
3	CASP1	1 hits
4	CD34	1 hits
5	CREB1	1 hits
6	CREBBP	1 hits
7	CREM	1 hits
8	EP300	1 hits
9	FOXA2	1 hits
10	G6PC	1 hits
11	G6PC2	1 hits
12	GCG	1 hits
13	GLIS3	1 hits
14	GPX1	1 hits
15	HNF1A	1 hits
16	INS	1 hits
17	KLRG1	1 hits
18	MAF	1 hits
19	MAFB	1 hits
20	MAFF	1 hits
21	MAPK1	1 hits
22	NA	1 hits
23	NEUROD1	1 hits
24	NEUROG3	1 hits
25	PAX4	1 hits
26	PAX6	1 hits
27	PDX1	1 hits
28	SLC2A2	1 hits
29	SLC37A4	1 hits
30	SST	1 hits
31	TCF7	1 hits
32	TCF7L2	1 hits

Related Sentences

#	PMID	Sentence
1	8613527	Chronic exposure of betaTC-6 cells to supraphysiologic concentrations of glucose decreases binding of the RIPE3b1 insulin gene transcription activator.
2	8613527	We have shown previously that chronic exposure of HIT-T15 cells to supraphysiologic glucose concentrations causes decreased insulin gene transcription and decreased binding activities of two beta-cell specific transcription factors, STF-1 and the RIPE3b1 activator, and have suggested that these events may provide a mechanism for glucose toxicity on beta-cell function.
3	8613527	Electromobility shift assays demonstrated that binding of a specific nuclear protein that recognizes the RIPE3b1 binding site of the insulin gene was markedly diminished in late passage cells chronically exposed to 11.1 mM glucose, whereas binding activities of STF-1 and ICE activators were unchanged.
4	8613527	Mutation of the RIPE3b1 binding site almost completely abolished insulin gene transcription as well as binding activity.
5	8613527	We conclude that chronic exposure of betaTC-6 cells to high glucose concentrations paradoxically decreases insulin gene transcription, in part, by decreasing activity of the trans-activating factor which binds to the RIPE3b1 sequence.
6	8613527	This study uniquely demonstrates that altered binding to the RIPE3b1 sequence mediates glucose toxicity in betaTC-6 cells, thus reinforcing the importance of this cis-acting element in the regulation of insulin gene transcription.
7	8613527	Chronic exposure of betaTC-6 cells to supraphysiologic concentrations of glucose decreases binding of the RIPE3b1 insulin gene transcription activator.
8	8613527	We have shown previously that chronic exposure of HIT-T15 cells to supraphysiologic glucose concentrations causes decreased insulin gene transcription and decreased binding activities of two beta-cell specific transcription factors, STF-1 and the RIPE3b1 activator, and have suggested that these events may provide a mechanism for glucose toxicity on beta-cell function.
9	8613527	Electromobility shift assays demonstrated that binding of a specific nuclear protein that recognizes the RIPE3b1 binding site of the insulin gene was markedly diminished in late passage cells chronically exposed to 11.1 mM glucose, whereas binding activities of STF-1 and ICE activators were unchanged.
10	8613527	Mutation of the RIPE3b1 binding site almost completely abolished insulin gene transcription as well as binding activity.
11	8613527	We conclude that chronic exposure of betaTC-6 cells to high glucose concentrations paradoxically decreases insulin gene transcription, in part, by decreasing activity of the trans-activating factor which binds to the RIPE3b1 sequence.
12	8613527	This study uniquely demonstrates that altered binding to the RIPE3b1 sequence mediates glucose toxicity in betaTC-6 cells, thus reinforcing the importance of this cis-acting element in the regulation of insulin gene transcription.
13	8613527	Chronic exposure of betaTC-6 cells to supraphysiologic concentrations of glucose decreases binding of the RIPE3b1 insulin gene transcription activator.
14	8613527	We have shown previously that chronic exposure of HIT-T15 cells to supraphysiologic glucose concentrations causes decreased insulin gene transcription and decreased binding activities of two beta-cell specific transcription factors, STF-1 and the RIPE3b1 activator, and have suggested that these events may provide a mechanism for glucose toxicity on beta-cell function.
15	8613527	Electromobility shift assays demonstrated that binding of a specific nuclear protein that recognizes the RIPE3b1 binding site of the insulin gene was markedly diminished in late passage cells chronically exposed to 11.1 mM glucose, whereas binding activities of STF-1 and ICE activators were unchanged.
16	8613527	Mutation of the RIPE3b1 binding site almost completely abolished insulin gene transcription as well as binding activity.
17	8613527	We conclude that chronic exposure of betaTC-6 cells to high glucose concentrations paradoxically decreases insulin gene transcription, in part, by decreasing activity of the trans-activating factor which binds to the RIPE3b1 sequence.
18	8613527	This study uniquely demonstrates that altered binding to the RIPE3b1 sequence mediates glucose toxicity in betaTC-6 cells, thus reinforcing the importance of this cis-acting element in the regulation of insulin gene transcription.
19	8613527	Chronic exposure of betaTC-6 cells to supraphysiologic concentrations of glucose decreases binding of the RIPE3b1 insulin gene transcription activator.
20	8613527	We have shown previously that chronic exposure of HIT-T15 cells to supraphysiologic glucose concentrations causes decreased insulin gene transcription and decreased binding activities of two beta-cell specific transcription factors, STF-1 and the RIPE3b1 activator, and have suggested that these events may provide a mechanism for glucose toxicity on beta-cell function.
21	8613527	Electromobility shift assays demonstrated that binding of a specific nuclear protein that recognizes the RIPE3b1 binding site of the insulin gene was markedly diminished in late passage cells chronically exposed to 11.1 mM glucose, whereas binding activities of STF-1 and ICE activators were unchanged.
22	8613527	Mutation of the RIPE3b1 binding site almost completely abolished insulin gene transcription as well as binding activity.
23	8613527	We conclude that chronic exposure of betaTC-6 cells to high glucose concentrations paradoxically decreases insulin gene transcription, in part, by decreasing activity of the trans-activating factor which binds to the RIPE3b1 sequence.
24	8613527	This study uniquely demonstrates that altered binding to the RIPE3b1 sequence mediates glucose toxicity in betaTC-6 cells, thus reinforcing the importance of this cis-acting element in the regulation of insulin gene transcription.
25	8613527	Chronic exposure of betaTC-6 cells to supraphysiologic concentrations of glucose decreases binding of the RIPE3b1 insulin gene transcription activator.
26	8613527	We have shown previously that chronic exposure of HIT-T15 cells to supraphysiologic glucose concentrations causes decreased insulin gene transcription and decreased binding activities of two beta-cell specific transcription factors, STF-1 and the RIPE3b1 activator, and have suggested that these events may provide a mechanism for glucose toxicity on beta-cell function.
27	8613527	Electromobility shift assays demonstrated that binding of a specific nuclear protein that recognizes the RIPE3b1 binding site of the insulin gene was markedly diminished in late passage cells chronically exposed to 11.1 mM glucose, whereas binding activities of STF-1 and ICE activators were unchanged.
28	8613527	Mutation of the RIPE3b1 binding site almost completely abolished insulin gene transcription as well as binding activity.
29	8613527	We conclude that chronic exposure of betaTC-6 cells to high glucose concentrations paradoxically decreases insulin gene transcription, in part, by decreasing activity of the trans-activating factor which binds to the RIPE3b1 sequence.
30	8613527	This study uniquely demonstrates that altered binding to the RIPE3b1 sequence mediates glucose toxicity in betaTC-6 cells, thus reinforcing the importance of this cis-acting element in the regulation of insulin gene transcription.
31	8613527	Chronic exposure of betaTC-6 cells to supraphysiologic concentrations of glucose decreases binding of the RIPE3b1 insulin gene transcription activator.
32	8613527	We have shown previously that chronic exposure of HIT-T15 cells to supraphysiologic glucose concentrations causes decreased insulin gene transcription and decreased binding activities of two beta-cell specific transcription factors, STF-1 and the RIPE3b1 activator, and have suggested that these events may provide a mechanism for glucose toxicity on beta-cell function.
33	8613527	Electromobility shift assays demonstrated that binding of a specific nuclear protein that recognizes the RIPE3b1 binding site of the insulin gene was markedly diminished in late passage cells chronically exposed to 11.1 mM glucose, whereas binding activities of STF-1 and ICE activators were unchanged.
34	8613527	Mutation of the RIPE3b1 binding site almost completely abolished insulin gene transcription as well as binding activity.
35	8613527	We conclude that chronic exposure of betaTC-6 cells to high glucose concentrations paradoxically decreases insulin gene transcription, in part, by decreasing activity of the trans-activating factor which binds to the RIPE3b1 sequence.
36	8613527	This study uniquely demonstrates that altered binding to the RIPE3b1 sequence mediates glucose toxicity in betaTC-6 cells, thus reinforcing the importance of this cis-acting element in the regulation of insulin gene transcription.
37	9022089	Chronic exposure of HIT-T15 cells to supraphysiologic glucose concentration diminishes insulin gene expression and decreased binding of two critical insulin gene transcription factors, STF-1 and RIPE-3b1 activator.
38	9022089	They regained binding of STF-1 and RIPE-3b1 activator and had a partial but minimal return of insulin mRNA expression.
39	9022089	In a second study, inclusion of somatostatin in the media-containing 11.1 mM glucose inhibited insulin secretion; however, despite this protection against beta cell exhaustion, dramatic decreases in insulin gene expression, STF-1 and RIPE-3b1 binding, and insulin gene promoter activity still occurred.
40	9022089	Chronic exposure of HIT-T15 cells to supraphysiologic glucose concentration diminishes insulin gene expression and decreased binding of two critical insulin gene transcription factors, STF-1 and RIPE-3b1 activator.
41	9022089	They regained binding of STF-1 and RIPE-3b1 activator and had a partial but minimal return of insulin mRNA expression.
42	9022089	In a second study, inclusion of somatostatin in the media-containing 11.1 mM glucose inhibited insulin secretion; however, despite this protection against beta cell exhaustion, dramatic decreases in insulin gene expression, STF-1 and RIPE-3b1 binding, and insulin gene promoter activity still occurred.
43	9022089	Chronic exposure of HIT-T15 cells to supraphysiologic glucose concentration diminishes insulin gene expression and decreased binding of two critical insulin gene transcription factors, STF-1 and RIPE-3b1 activator.
44	9022089	They regained binding of STF-1 and RIPE-3b1 activator and had a partial but minimal return of insulin mRNA expression.
45	9022089	In a second study, inclusion of somatostatin in the media-containing 11.1 mM glucose inhibited insulin secretion; however, despite this protection against beta cell exhaustion, dramatic decreases in insulin gene expression, STF-1 and RIPE-3b1 binding, and insulin gene promoter activity still occurred.
46	9604866	Reconstitution of glucotoxic HIT-T15 cells with somatostatin transcription factor-1 partially restores insulin promoter activity.
47	9604866	Furthermore, decreases in insulin gene transcription and binding activity of two essential beta-cell transcription factors, somatostatin transcription factor-1 (STF-1; also known as GSTF, IDX-1, IPF-1, PDX-1, and GSF) and RIPE-3b1 activator, are associated with this glucotoxic effect.
48	9604866	In this study, we observed that the loss of RIPE-3b1 occurs much earlier (79% decrease at passage [p]81) than the loss of STF-1 (65% decrease at p104), with abolishment of both factors by p122.
49	9604866	Since the STF-1, but not the RIPE-3b1 activator, gene has been cloned, we examined its restorative effects on insulin gene promoter activity after reconstitution with STF-1 cDNA.
50	9604866	Compared with basal levels, we observed a trend toward an increase in insulin promoter activity in intermediate passage cells with STF-1 transfection (1.43-fold) that became a significant increase when E2-5 was cotransfected (1.78-fold).
51	9604866	In late passage cells, transfection of STF-1 alone significantly stimulated a 2.2-fold increase in the insulin promoter activity.
52	9604866	Cotransfection of STF-1 and E2-5 in late passage cells stimulated insulin promoter activity 2.8-fold, which was 40% of the activity observed in early passage cells.
53	9604866	Control studies in glucotoxic betaTC-6 cells deficient in RIPE-3b1 activator but not STF-1 did not demonstrate an increase in insulin promoter activity after STF-1 transfection.
54	9604866	We conclude that loss of RIPE-3b1 activity precedes loss of STF-1 activity in glucotoxic HIT-T15 cells and that defective promoter activity can be partially restored by STF-1 transfection and predict that eventual cloning of the RIPE-3b1 gene will allow cotransfection studies with both factors that will allow full reconstitution of insulin promoter activity.
55	9604866	Reconstitution of glucotoxic HIT-T15 cells with somatostatin transcription factor-1 partially restores insulin promoter activity.
56	9604866	Furthermore, decreases in insulin gene transcription and binding activity of two essential beta-cell transcription factors, somatostatin transcription factor-1 (STF-1; also known as GSTF, IDX-1, IPF-1, PDX-1, and GSF) and RIPE-3b1 activator, are associated with this glucotoxic effect.
57	9604866	In this study, we observed that the loss of RIPE-3b1 occurs much earlier (79% decrease at passage [p]81) than the loss of STF-1 (65% decrease at p104), with abolishment of both factors by p122.
58	9604866	Since the STF-1, but not the RIPE-3b1 activator, gene has been cloned, we examined its restorative effects on insulin gene promoter activity after reconstitution with STF-1 cDNA.
59	9604866	Compared with basal levels, we observed a trend toward an increase in insulin promoter activity in intermediate passage cells with STF-1 transfection (1.43-fold) that became a significant increase when E2-5 was cotransfected (1.78-fold).
60	9604866	In late passage cells, transfection of STF-1 alone significantly stimulated a 2.2-fold increase in the insulin promoter activity.
61	9604866	Cotransfection of STF-1 and E2-5 in late passage cells stimulated insulin promoter activity 2.8-fold, which was 40% of the activity observed in early passage cells.
62	9604866	Control studies in glucotoxic betaTC-6 cells deficient in RIPE-3b1 activator but not STF-1 did not demonstrate an increase in insulin promoter activity after STF-1 transfection.
63	9604866	We conclude that loss of RIPE-3b1 activity precedes loss of STF-1 activity in glucotoxic HIT-T15 cells and that defective promoter activity can be partially restored by STF-1 transfection and predict that eventual cloning of the RIPE-3b1 gene will allow cotransfection studies with both factors that will allow full reconstitution of insulin promoter activity.
64	9604866	Reconstitution of glucotoxic HIT-T15 cells with somatostatin transcription factor-1 partially restores insulin promoter activity.
65	9604866	Furthermore, decreases in insulin gene transcription and binding activity of two essential beta-cell transcription factors, somatostatin transcription factor-1 (STF-1; also known as GSTF, IDX-1, IPF-1, PDX-1, and GSF) and RIPE-3b1 activator, are associated with this glucotoxic effect.
66	9604866	In this study, we observed that the loss of RIPE-3b1 occurs much earlier (79% decrease at passage [p]81) than the loss of STF-1 (65% decrease at p104), with abolishment of both factors by p122.
67	9604866	Since the STF-1, but not the RIPE-3b1 activator, gene has been cloned, we examined its restorative effects on insulin gene promoter activity after reconstitution with STF-1 cDNA.
68	9604866	Compared with basal levels, we observed a trend toward an increase in insulin promoter activity in intermediate passage cells with STF-1 transfection (1.43-fold) that became a significant increase when E2-5 was cotransfected (1.78-fold).
69	9604866	In late passage cells, transfection of STF-1 alone significantly stimulated a 2.2-fold increase in the insulin promoter activity.
70	9604866	Cotransfection of STF-1 and E2-5 in late passage cells stimulated insulin promoter activity 2.8-fold, which was 40% of the activity observed in early passage cells.
71	9604866	Control studies in glucotoxic betaTC-6 cells deficient in RIPE-3b1 activator but not STF-1 did not demonstrate an increase in insulin promoter activity after STF-1 transfection.
72	9604866	We conclude that loss of RIPE-3b1 activity precedes loss of STF-1 activity in glucotoxic HIT-T15 cells and that defective promoter activity can be partially restored by STF-1 transfection and predict that eventual cloning of the RIPE-3b1 gene will allow cotransfection studies with both factors that will allow full reconstitution of insulin promoter activity.
73	9604866	Reconstitution of glucotoxic HIT-T15 cells with somatostatin transcription factor-1 partially restores insulin promoter activity.
74	9604866	Furthermore, decreases in insulin gene transcription and binding activity of two essential beta-cell transcription factors, somatostatin transcription factor-1 (STF-1; also known as GSTF, IDX-1, IPF-1, PDX-1, and GSF) and RIPE-3b1 activator, are associated with this glucotoxic effect.
75	9604866	In this study, we observed that the loss of RIPE-3b1 occurs much earlier (79% decrease at passage [p]81) than the loss of STF-1 (65% decrease at p104), with abolishment of both factors by p122.
76	9604866	Since the STF-1, but not the RIPE-3b1 activator, gene has been cloned, we examined its restorative effects on insulin gene promoter activity after reconstitution with STF-1 cDNA.
77	9604866	Compared with basal levels, we observed a trend toward an increase in insulin promoter activity in intermediate passage cells with STF-1 transfection (1.43-fold) that became a significant increase when E2-5 was cotransfected (1.78-fold).
78	9604866	In late passage cells, transfection of STF-1 alone significantly stimulated a 2.2-fold increase in the insulin promoter activity.
79	9604866	Cotransfection of STF-1 and E2-5 in late passage cells stimulated insulin promoter activity 2.8-fold, which was 40% of the activity observed in early passage cells.
80	9604866	Control studies in glucotoxic betaTC-6 cells deficient in RIPE-3b1 activator but not STF-1 did not demonstrate an increase in insulin promoter activity after STF-1 transfection.
81	9604866	We conclude that loss of RIPE-3b1 activity precedes loss of STF-1 activity in glucotoxic HIT-T15 cells and that defective promoter activity can be partially restored by STF-1 transfection and predict that eventual cloning of the RIPE-3b1 gene will allow cotransfection studies with both factors that will allow full reconstitution of insulin promoter activity.
82	9604866	Reconstitution of glucotoxic HIT-T15 cells with somatostatin transcription factor-1 partially restores insulin promoter activity.
83	9604866	Furthermore, decreases in insulin gene transcription and binding activity of two essential beta-cell transcription factors, somatostatin transcription factor-1 (STF-1; also known as GSTF, IDX-1, IPF-1, PDX-1, and GSF) and RIPE-3b1 activator, are associated with this glucotoxic effect.
84	9604866	In this study, we observed that the loss of RIPE-3b1 occurs much earlier (79% decrease at passage [p]81) than the loss of STF-1 (65% decrease at p104), with abolishment of both factors by p122.
85	9604866	Since the STF-1, but not the RIPE-3b1 activator, gene has been cloned, we examined its restorative effects on insulin gene promoter activity after reconstitution with STF-1 cDNA.
86	9604866	Compared with basal levels, we observed a trend toward an increase in insulin promoter activity in intermediate passage cells with STF-1 transfection (1.43-fold) that became a significant increase when E2-5 was cotransfected (1.78-fold).
87	9604866	In late passage cells, transfection of STF-1 alone significantly stimulated a 2.2-fold increase in the insulin promoter activity.
88	9604866	Cotransfection of STF-1 and E2-5 in late passage cells stimulated insulin promoter activity 2.8-fold, which was 40% of the activity observed in early passage cells.
89	9604866	Control studies in glucotoxic betaTC-6 cells deficient in RIPE-3b1 activator but not STF-1 did not demonstrate an increase in insulin promoter activity after STF-1 transfection.
90	9604866	We conclude that loss of RIPE-3b1 activity precedes loss of STF-1 activity in glucotoxic HIT-T15 cells and that defective promoter activity can be partially restored by STF-1 transfection and predict that eventual cloning of the RIPE-3b1 gene will allow cotransfection studies with both factors that will allow full reconstitution of insulin promoter activity.
91	10485916	Addition of NAC or AG to the culture medium at least partially prevented decreases in insulin mRNA, insulin gene promoter activity, DNA binding of two important insulin promoter transcription factors (PDX-1/STF-1 and RIPE-3b1 activator), insulin content, and glucose-induced insulin secretion.
92	10485916	Both drugs prevented a rise in blood oxidative stress markers (8-hydroxy-2'-deoxyguanosine and malondialdehyde + 4-hydroxy-2-nonenal), and partially prevented hyperglycemia, glucose intolerance, defective insulin secretion as well as decrements in beta cell insulin content, insulin gene expression, and PDX-1 (STF-1) binding to the insulin gene promoter.
93	11024035	Transcription factors (PDX-1 and HNF-1 alpha) binding to A elements are critical regulators of insulin gene expression and/or pancreatic development.
94	11024035	In addition, RIPE3b1- and A2-specific activators respond differently to glucose, suggesting that their overlapping binding specificity and functional cooperation may play an important role in regulating insulin gene expression.
95	12011435	Identification of beta-cell-specific insulin gene transcription factor RIPE3b1 as mammalian MafA.
96	12011435	Of the three critical enhancer elements that mediate beta-cell-specific and glucose-responsive expression of the insulin gene, only the identity of the transcription factor binding to the RIPE3b element (RIPE3b1) has remained elusive.
97	12011435	Here, we report cloning of the human mafA (hMafA) and demonstrate that it can specifically bind the insulin enhancer element RIPE3b and activate insulin-gene expression.
98	12011435	Identification of beta-cell-specific insulin gene transcription factor RIPE3b1 as mammalian MafA.
99	12011435	Of the three critical enhancer elements that mediate beta-cell-specific and glucose-responsive expression of the insulin gene, only the identity of the transcription factor binding to the RIPE3b element (RIPE3b1) has remained elusive.
100	12011435	Here, we report cloning of the human mafA (hMafA) and demonstrate that it can specifically bind the insulin enhancer element RIPE3b and activate insulin-gene expression.
101	12011435	Identification of beta-cell-specific insulin gene transcription factor RIPE3b1 as mammalian MafA.
102	12011435	Of the three critical enhancer elements that mediate beta-cell-specific and glucose-responsive expression of the insulin gene, only the identity of the transcription factor binding to the RIPE3b element (RIPE3b1) has remained elusive.
103	12011435	Here, we report cloning of the human mafA (hMafA) and demonstrate that it can specifically bind the insulin enhancer element RIPE3b and activate insulin-gene expression.
104	15923615	MafA is a key regulator of glucose-stimulated insulin secretion.
105	15923615	MafA is a transcription factor that binds to the promoter in the insulin gene and has been postulated to regulate insulin transcription in response to serum glucose levels, but there is no current in vivo evidence to support this hypothesis.
106	15923615	To analyze the role of MafA in insulin transcription and glucose homeostasis in vivo, we generated MafA-deficient mice.
107	15923615	Further analysis revealed that insulin 1, insulin 2, Pdx1, Beta2, and Glut-2 transcripts are diminished in MafA-deficient mice.
108	15923615	These results show that MafA is a key regulator of glucose-stimulated insulin secretion in vivo.
109	15923615	MafA is a key regulator of glucose-stimulated insulin secretion.
110	15923615	MafA is a transcription factor that binds to the promoter in the insulin gene and has been postulated to regulate insulin transcription in response to serum glucose levels, but there is no current in vivo evidence to support this hypothesis.
111	15923615	To analyze the role of MafA in insulin transcription and glucose homeostasis in vivo, we generated MafA-deficient mice.
112	15923615	Further analysis revealed that insulin 1, insulin 2, Pdx1, Beta2, and Glut-2 transcripts are diminished in MafA-deficient mice.
113	15923615	These results show that MafA is a key regulator of glucose-stimulated insulin secretion in vivo.
114	15923615	MafA is a key regulator of glucose-stimulated insulin secretion.
115	15923615	MafA is a transcription factor that binds to the promoter in the insulin gene and has been postulated to regulate insulin transcription in response to serum glucose levels, but there is no current in vivo evidence to support this hypothesis.
116	15923615	To analyze the role of MafA in insulin transcription and glucose homeostasis in vivo, we generated MafA-deficient mice.
117	15923615	Further analysis revealed that insulin 1, insulin 2, Pdx1, Beta2, and Glut-2 transcripts are diminished in MafA-deficient mice.
118	15923615	These results show that MafA is a key regulator of glucose-stimulated insulin secretion in vivo.
119	15923615	MafA is a key regulator of glucose-stimulated insulin secretion.
120	15923615	MafA is a transcription factor that binds to the promoter in the insulin gene and has been postulated to regulate insulin transcription in response to serum glucose levels, but there is no current in vivo evidence to support this hypothesis.
121	15923615	To analyze the role of MafA in insulin transcription and glucose homeostasis in vivo, we generated MafA-deficient mice.
122	15923615	Further analysis revealed that insulin 1, insulin 2, Pdx1, Beta2, and Glut-2 transcripts are diminished in MafA-deficient mice.
123	15923615	These results show that MafA is a key regulator of glucose-stimulated insulin secretion in vivo.
124	15923615	MafA is a key regulator of glucose-stimulated insulin secretion.
125	15923615	MafA is a transcription factor that binds to the promoter in the insulin gene and has been postulated to regulate insulin transcription in response to serum glucose levels, but there is no current in vivo evidence to support this hypothesis.
126	15923615	To analyze the role of MafA in insulin transcription and glucose homeostasis in vivo, we generated MafA-deficient mice.
127	15923615	Further analysis revealed that insulin 1, insulin 2, Pdx1, Beta2, and Glut-2 transcripts are diminished in MafA-deficient mice.
128	15923615	These results show that MafA is a key regulator of glucose-stimulated insulin secretion in vivo.
129	16050808	The transcription factor MafA/RIPE3b1 is an important regulator of insulin gene expression.
130	16050808	MafA binds to the insulin enhancer element RIPE3b (C1-A2), now designated as insulin MARE (Maf response element).
131	16050808	Surprisingly, instead of interfering with each other's binding activity, the MafA and the A2-binding factors co-operatively activated insulin gene expression.
132	16050808	The transcription factor MafA/RIPE3b1 is an important regulator of insulin gene expression.
133	16050808	MafA binds to the insulin enhancer element RIPE3b (C1-A2), now designated as insulin MARE (Maf response element).
134	16050808	Surprisingly, instead of interfering with each other's binding activity, the MafA and the A2-binding factors co-operatively activated insulin gene expression.
135	16050808	The transcription factor MafA/RIPE3b1 is an important regulator of insulin gene expression.
136	16050808	MafA binds to the insulin enhancer element RIPE3b (C1-A2), now designated as insulin MARE (Maf response element).
137	16050808	Surprisingly, instead of interfering with each other's binding activity, the MafA and the A2-binding factors co-operatively activated insulin gene expression.
138	16580660	A switch from MafB to MafA expression accompanies differentiation to pancreatic beta-cells.
139	16580660	Major insulin gene transcription factors, such as PDX-1 or NeuroD1, have equally important roles in pancreatic development and the differentiation of pancreatic endocrine cells.
140	16580660	Previously, we identified and cloned another critical insulin gene transcription factor MafA (RIPE3b1) and reported that other Maf factors were expressed in pancreatic endocrine cells.
141	16580660	Ectopically expressed large-Maf factors, MafA, MafB, or cMaf, induced expression from insulin and glucagon reporter constructs, demonstrating a redundancy in their function.
142	16580660	Yet in adult pancreas, cMaf was expressed in both alpha- and beta-cells, and MafA and MafB showed selective expression in the beta- and alpha-cells, respectively.
143	16580660	Furthermore, the MafB to MafA transition follows induction of PDX-1 expression (Pdx-1(high)) in MafB+ Ins+ cells.
144	16580660	A switch from MafB to MafA expression accompanies differentiation to pancreatic beta-cells.
145	16580660	Major insulin gene transcription factors, such as PDX-1 or NeuroD1, have equally important roles in pancreatic development and the differentiation of pancreatic endocrine cells.
146	16580660	Previously, we identified and cloned another critical insulin gene transcription factor MafA (RIPE3b1) and reported that other Maf factors were expressed in pancreatic endocrine cells.
147	16580660	Ectopically expressed large-Maf factors, MafA, MafB, or cMaf, induced expression from insulin and glucagon reporter constructs, demonstrating a redundancy in their function.
148	16580660	Yet in adult pancreas, cMaf was expressed in both alpha- and beta-cells, and MafA and MafB showed selective expression in the beta- and alpha-cells, respectively.
149	16580660	Furthermore, the MafB to MafA transition follows induction of PDX-1 expression (Pdx-1(high)) in MafB+ Ins+ cells.
150	16580660	A switch from MafB to MafA expression accompanies differentiation to pancreatic beta-cells.
151	16580660	Major insulin gene transcription factors, such as PDX-1 or NeuroD1, have equally important roles in pancreatic development and the differentiation of pancreatic endocrine cells.
152	16580660	Previously, we identified and cloned another critical insulin gene transcription factor MafA (RIPE3b1) and reported that other Maf factors were expressed in pancreatic endocrine cells.
153	16580660	Ectopically expressed large-Maf factors, MafA, MafB, or cMaf, induced expression from insulin and glucagon reporter constructs, demonstrating a redundancy in their function.
154	16580660	Yet in adult pancreas, cMaf was expressed in both alpha- and beta-cells, and MafA and MafB showed selective expression in the beta- and alpha-cells, respectively.
155	16580660	Furthermore, the MafB to MafA transition follows induction of PDX-1 expression (Pdx-1(high)) in MafB+ Ins+ cells.
156	16580660	A switch from MafB to MafA expression accompanies differentiation to pancreatic beta-cells.
157	16580660	Major insulin gene transcription factors, such as PDX-1 or NeuroD1, have equally important roles in pancreatic development and the differentiation of pancreatic endocrine cells.
158	16580660	Previously, we identified and cloned another critical insulin gene transcription factor MafA (RIPE3b1) and reported that other Maf factors were expressed in pancreatic endocrine cells.
159	16580660	Ectopically expressed large-Maf factors, MafA, MafB, or cMaf, induced expression from insulin and glucagon reporter constructs, demonstrating a redundancy in their function.
160	16580660	Yet in adult pancreas, cMaf was expressed in both alpha- and beta-cells, and MafA and MafB showed selective expression in the beta- and alpha-cells, respectively.
161	16580660	Furthermore, the MafB to MafA transition follows induction of PDX-1 expression (Pdx-1(high)) in MafB+ Ins+ cells.
162	16580660	A switch from MafB to MafA expression accompanies differentiation to pancreatic beta-cells.
163	16580660	Major insulin gene transcription factors, such as PDX-1 or NeuroD1, have equally important roles in pancreatic development and the differentiation of pancreatic endocrine cells.
164	16580660	Previously, we identified and cloned another critical insulin gene transcription factor MafA (RIPE3b1) and reported that other Maf factors were expressed in pancreatic endocrine cells.
165	16580660	Ectopically expressed large-Maf factors, MafA, MafB, or cMaf, induced expression from insulin and glucagon reporter constructs, demonstrating a redundancy in their function.
166	16580660	Yet in adult pancreas, cMaf was expressed in both alpha- and beta-cells, and MafA and MafB showed selective expression in the beta- and alpha-cells, respectively.
167	16580660	Furthermore, the MafB to MafA transition follows induction of PDX-1 expression (Pdx-1(high)) in MafB+ Ins+ cells.
168	16772326	Genes underrepresented in ZDF islets were either unaffected (Glut-2, Kir6.2, Rab3), stimulated (voltage-dependent Ca(2+) channel subunit alpha1D, CPT2, SUR2, rab9, syt13), or inhibited (syntaxin 7, secretogranin-2) by SREBP-1c inhibition.
169	16772326	Correspondingly, SREBP-1c DN largely corrected decreases in the expression of the transcription factors Pdx-1 and MafA but did not affect the abnormalities in Pax6, Arx, hepatic nuclear factor-1alpha (HNF1alpha), HNF3beta/Forkhead box-a2 (Foxa2), inducible cyclic AMP early repressor (ICER), or transcription factor 7-like 2 (TCF7L2) expression observed in ZDF islets.
170	17045527	Co-incident with these changes are profound alterations in insulin gene expression, which involve greatly diminished levels of two transcription factors, MafA and Pdx-1.
171	18450959	Endoplasmic reticulum stress-induced activation of activating transcription factor 6 decreases insulin gene expression via up-regulation of orphan nuclear receptor small heterodimer partner.
172	18450959	Here we examined whether ER stress-induced activation of activating transcription factor (ATF)-6 impairs insulin gene expression via up-regulation of the orphan nuclear receptor small heterodimer partner (SHP; NR0B2), which has been shown to play a role in beta-cell dysfunction.
173	18450959	We examined whether ER stress decreases insulin gene expression, and this process is mediated by ATF6.
174	18450959	A small interfering RNA that targeted SHP was used to determine whether the effect of ATF6 on insulin gene expression is mediated by SHP.
175	18450959	ATF6 inhibited insulin promoter activity, whereas X-box binding protein-1 and ATF4 did not.
176	18450959	Adenovirus-mediated overexpression of active form of ATF6 in INS-1 cells impaired insulin gene expression and secretion.
177	18450959	ATF6 also down-regulated pancreatic duodenal homeobox factor-1 and RIPE3b1/MafA gene expression and repressed the cooperative action of pancreatic duodenal homeobox factor-1, RIPE3b1/MafA, and beta-cell E box transactivator 2 in stimulating insulin transcription.
178	18450959	The ATF6-induced suppression of insulin gene expression was associated with up-regulation of SHP gene expression.
179	18753309	Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression.
180	18753309	Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP/G6PC2) is a major autoantigen in both mouse and human type 1 diabetes.
181	18753309	Chromatin immunoprecipitation (ChIP) assays have shown that the IGRP promoter binds the islet-enriched transcription factors Pax-6 and BETA2.
182	18753309	We show here, again using ChIP assays, that the IGRP promoter also binds the islet-enriched transcription factors MafA and Foxa2.
183	18753309	ChiP assays have shown that the islet-enriched transcription factor Pdx-1 also binds the IGRP promoter, but mutational analysis of four Pdx-1 binding sites in the proximal IGRP promoter revealed surprisingly little effect of Pdx-1 binding on IGRP fusion gene expression in betaTC-3 cells.
184	18753309	These data suggest that the same group of islet-enriched transcription factors, namely Pdx-1, Pax-6, MafA, BETA2, and Foxa2, directly or indirectly regulate expression of the two major autoantigens in type 1 diabetes.
185	18753309	Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression.
186	18753309	Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP/G6PC2) is a major autoantigen in both mouse and human type 1 diabetes.
187	18753309	Chromatin immunoprecipitation (ChIP) assays have shown that the IGRP promoter binds the islet-enriched transcription factors Pax-6 and BETA2.
188	18753309	We show here, again using ChIP assays, that the IGRP promoter also binds the islet-enriched transcription factors MafA and Foxa2.
189	18753309	ChiP assays have shown that the islet-enriched transcription factor Pdx-1 also binds the IGRP promoter, but mutational analysis of four Pdx-1 binding sites in the proximal IGRP promoter revealed surprisingly little effect of Pdx-1 binding on IGRP fusion gene expression in betaTC-3 cells.
190	18753309	These data suggest that the same group of islet-enriched transcription factors, namely Pdx-1, Pax-6, MafA, BETA2, and Foxa2, directly or indirectly regulate expression of the two major autoantigens in type 1 diabetes.
191	18753309	Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression.
192	18753309	Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP/G6PC2) is a major autoantigen in both mouse and human type 1 diabetes.
193	18753309	Chromatin immunoprecipitation (ChIP) assays have shown that the IGRP promoter binds the islet-enriched transcription factors Pax-6 and BETA2.
194	18753309	We show here, again using ChIP assays, that the IGRP promoter also binds the islet-enriched transcription factors MafA and Foxa2.
195	18753309	ChiP assays have shown that the islet-enriched transcription factor Pdx-1 also binds the IGRP promoter, but mutational analysis of four Pdx-1 binding sites in the proximal IGRP promoter revealed surprisingly little effect of Pdx-1 binding on IGRP fusion gene expression in betaTC-3 cells.
196	18753309	These data suggest that the same group of islet-enriched transcription factors, namely Pdx-1, Pax-6, MafA, BETA2, and Foxa2, directly or indirectly regulate expression of the two major autoantigens in type 1 diabetes.
197	19407223	p38 MAPK is a major regulator of MafA protein stability under oxidative stress.
198	19407223	Increased expression of MafA results in improved glucose-stimulated insulin secretion and beta-cell function.
199	19407223	We demonstrate that MafA protein stability in MIN6 cells and isolated mouse islets is regulated by both p38 MAPK and glycogen synthase kinase 3.
200	19407223	Inhibiting p38 MAPK enhanced MafA stability in cells grown under both low and high concentrations of glucose.
201	19407223	We also show that the N-terminal domain of MafA plays a major role in p38 MAPK-mediated degradation; simultaneous mutation of both threonines 57 and 134 into alanines in MafA was sufficient to prevent this degradation.
202	19407223	Under oxidative stress, a condition detrimental to beta-cell function, a decrease in MafA stability was associated with a concomitant increase in active p38 MAPK.
203	19407223	Interestingly, inhibiting p38 MAPK but not glycogen synthase kinase 3 prevented oxidative stress-dependent degradation of MafA.
204	19407223	These results suggest that the p38 MAPK pathway may represent a common mechanism for regulating MafA levels under oxidative stress and basal and stimulatory glucose concentrations.
205	19407223	Therefore, preventing p38 MAPK-mediated degradation of MafA represents a novel approach to improve beta-cell function.
206	19407223	p38 MAPK is a major regulator of MafA protein stability under oxidative stress.
207	19407223	Increased expression of MafA results in improved glucose-stimulated insulin secretion and beta-cell function.
208	19407223	We demonstrate that MafA protein stability in MIN6 cells and isolated mouse islets is regulated by both p38 MAPK and glycogen synthase kinase 3.
209	19407223	Inhibiting p38 MAPK enhanced MafA stability in cells grown under both low and high concentrations of glucose.
210	19407223	We also show that the N-terminal domain of MafA plays a major role in p38 MAPK-mediated degradation; simultaneous mutation of both threonines 57 and 134 into alanines in MafA was sufficient to prevent this degradation.
211	19407223	Under oxidative stress, a condition detrimental to beta-cell function, a decrease in MafA stability was associated with a concomitant increase in active p38 MAPK.
212	19407223	Interestingly, inhibiting p38 MAPK but not glycogen synthase kinase 3 prevented oxidative stress-dependent degradation of MafA.
213	19407223	These results suggest that the p38 MAPK pathway may represent a common mechanism for regulating MafA levels under oxidative stress and basal and stimulatory glucose concentrations.
214	19407223	Therefore, preventing p38 MAPK-mediated degradation of MafA represents a novel approach to improve beta-cell function.
215	19407223	p38 MAPK is a major regulator of MafA protein stability under oxidative stress.
216	19407223	Increased expression of MafA results in improved glucose-stimulated insulin secretion and beta-cell function.
217	19407223	We demonstrate that MafA protein stability in MIN6 cells and isolated mouse islets is regulated by both p38 MAPK and glycogen synthase kinase 3.
218	19407223	Inhibiting p38 MAPK enhanced MafA stability in cells grown under both low and high concentrations of glucose.
219	19407223	We also show that the N-terminal domain of MafA plays a major role in p38 MAPK-mediated degradation; simultaneous mutation of both threonines 57 and 134 into alanines in MafA was sufficient to prevent this degradation.
220	19407223	Under oxidative stress, a condition detrimental to beta-cell function, a decrease in MafA stability was associated with a concomitant increase in active p38 MAPK.
221	19407223	Interestingly, inhibiting p38 MAPK but not glycogen synthase kinase 3 prevented oxidative stress-dependent degradation of MafA.
222	19407223	These results suggest that the p38 MAPK pathway may represent a common mechanism for regulating MafA levels under oxidative stress and basal and stimulatory glucose concentrations.
223	19407223	Therefore, preventing p38 MAPK-mediated degradation of MafA represents a novel approach to improve beta-cell function.
224	19407223	p38 MAPK is a major regulator of MafA protein stability under oxidative stress.
225	19407223	Increased expression of MafA results in improved glucose-stimulated insulin secretion and beta-cell function.
226	19407223	We demonstrate that MafA protein stability in MIN6 cells and isolated mouse islets is regulated by both p38 MAPK and glycogen synthase kinase 3.
227	19407223	Inhibiting p38 MAPK enhanced MafA stability in cells grown under both low and high concentrations of glucose.
228	19407223	We also show that the N-terminal domain of MafA plays a major role in p38 MAPK-mediated degradation; simultaneous mutation of both threonines 57 and 134 into alanines in MafA was sufficient to prevent this degradation.
229	19407223	Under oxidative stress, a condition detrimental to beta-cell function, a decrease in MafA stability was associated with a concomitant increase in active p38 MAPK.
230	19407223	Interestingly, inhibiting p38 MAPK but not glycogen synthase kinase 3 prevented oxidative stress-dependent degradation of MafA.
231	19407223	These results suggest that the p38 MAPK pathway may represent a common mechanism for regulating MafA levels under oxidative stress and basal and stimulatory glucose concentrations.
232	19407223	Therefore, preventing p38 MAPK-mediated degradation of MafA represents a novel approach to improve beta-cell function.
233	19407223	p38 MAPK is a major regulator of MafA protein stability under oxidative stress.
234	19407223	Increased expression of MafA results in improved glucose-stimulated insulin secretion and beta-cell function.
235	19407223	We demonstrate that MafA protein stability in MIN6 cells and isolated mouse islets is regulated by both p38 MAPK and glycogen synthase kinase 3.
236	19407223	Inhibiting p38 MAPK enhanced MafA stability in cells grown under both low and high concentrations of glucose.
237	19407223	We also show that the N-terminal domain of MafA plays a major role in p38 MAPK-mediated degradation; simultaneous mutation of both threonines 57 and 134 into alanines in MafA was sufficient to prevent this degradation.
238	19407223	Under oxidative stress, a condition detrimental to beta-cell function, a decrease in MafA stability was associated with a concomitant increase in active p38 MAPK.
239	19407223	Interestingly, inhibiting p38 MAPK but not glycogen synthase kinase 3 prevented oxidative stress-dependent degradation of MafA.
240	19407223	These results suggest that the p38 MAPK pathway may represent a common mechanism for regulating MafA levels under oxidative stress and basal and stimulatory glucose concentrations.
241	19407223	Therefore, preventing p38 MAPK-mediated degradation of MafA represents a novel approach to improve beta-cell function.
242	19407223	p38 MAPK is a major regulator of MafA protein stability under oxidative stress.
243	19407223	Increased expression of MafA results in improved glucose-stimulated insulin secretion and beta-cell function.
244	19407223	We demonstrate that MafA protein stability in MIN6 cells and isolated mouse islets is regulated by both p38 MAPK and glycogen synthase kinase 3.
245	19407223	Inhibiting p38 MAPK enhanced MafA stability in cells grown under both low and high concentrations of glucose.
246	19407223	We also show that the N-terminal domain of MafA plays a major role in p38 MAPK-mediated degradation; simultaneous mutation of both threonines 57 and 134 into alanines in MafA was sufficient to prevent this degradation.
247	19407223	Under oxidative stress, a condition detrimental to beta-cell function, a decrease in MafA stability was associated with a concomitant increase in active p38 MAPK.
248	19407223	Interestingly, inhibiting p38 MAPK but not glycogen synthase kinase 3 prevented oxidative stress-dependent degradation of MafA.
249	19407223	These results suggest that the p38 MAPK pathway may represent a common mechanism for regulating MafA levels under oxidative stress and basal and stimulatory glucose concentrations.
250	19407223	Therefore, preventing p38 MAPK-mediated degradation of MafA represents a novel approach to improve beta-cell function.
251	19407223	p38 MAPK is a major regulator of MafA protein stability under oxidative stress.
252	19407223	Increased expression of MafA results in improved glucose-stimulated insulin secretion and beta-cell function.
253	19407223	We demonstrate that MafA protein stability in MIN6 cells and isolated mouse islets is regulated by both p38 MAPK and glycogen synthase kinase 3.
254	19407223	Inhibiting p38 MAPK enhanced MafA stability in cells grown under both low and high concentrations of glucose.
255	19407223	We also show that the N-terminal domain of MafA plays a major role in p38 MAPK-mediated degradation; simultaneous mutation of both threonines 57 and 134 into alanines in MafA was sufficient to prevent this degradation.
256	19407223	Under oxidative stress, a condition detrimental to beta-cell function, a decrease in MafA stability was associated with a concomitant increase in active p38 MAPK.
257	19407223	Interestingly, inhibiting p38 MAPK but not glycogen synthase kinase 3 prevented oxidative stress-dependent degradation of MafA.
258	19407223	These results suggest that the p38 MAPK pathway may represent a common mechanism for regulating MafA levels under oxidative stress and basal and stimulatory glucose concentrations.
259	19407223	Therefore, preventing p38 MAPK-mediated degradation of MafA represents a novel approach to improve beta-cell function.
260	19407223	p38 MAPK is a major regulator of MafA protein stability under oxidative stress.
261	19407223	Increased expression of MafA results in improved glucose-stimulated insulin secretion and beta-cell function.
262	19407223	We demonstrate that MafA protein stability in MIN6 cells and isolated mouse islets is regulated by both p38 MAPK and glycogen synthase kinase 3.
263	19407223	Inhibiting p38 MAPK enhanced MafA stability in cells grown under both low and high concentrations of glucose.
264	19407223	We also show that the N-terminal domain of MafA plays a major role in p38 MAPK-mediated degradation; simultaneous mutation of both threonines 57 and 134 into alanines in MafA was sufficient to prevent this degradation.
265	19407223	Under oxidative stress, a condition detrimental to beta-cell function, a decrease in MafA stability was associated with a concomitant increase in active p38 MAPK.
266	19407223	Interestingly, inhibiting p38 MAPK but not glycogen synthase kinase 3 prevented oxidative stress-dependent degradation of MafA.
267	19407223	These results suggest that the p38 MAPK pathway may represent a common mechanism for regulating MafA levels under oxidative stress and basal and stimulatory glucose concentrations.
268	19407223	Therefore, preventing p38 MAPK-mediated degradation of MafA represents a novel approach to improve beta-cell function.
269	19407223	p38 MAPK is a major regulator of MafA protein stability under oxidative stress.
270	19407223	Increased expression of MafA results in improved glucose-stimulated insulin secretion and beta-cell function.
271	19407223	We demonstrate that MafA protein stability in MIN6 cells and isolated mouse islets is regulated by both p38 MAPK and glycogen synthase kinase 3.
272	19407223	Inhibiting p38 MAPK enhanced MafA stability in cells grown under both low and high concentrations of glucose.
273	19407223	We also show that the N-terminal domain of MafA plays a major role in p38 MAPK-mediated degradation; simultaneous mutation of both threonines 57 and 134 into alanines in MafA was sufficient to prevent this degradation.
274	19407223	Under oxidative stress, a condition detrimental to beta-cell function, a decrease in MafA stability was associated with a concomitant increase in active p38 MAPK.
275	19407223	Interestingly, inhibiting p38 MAPK but not glycogen synthase kinase 3 prevented oxidative stress-dependent degradation of MafA.
276	19407223	These results suggest that the p38 MAPK pathway may represent a common mechanism for regulating MafA levels under oxidative stress and basal and stimulatory glucose concentrations.
277	19407223	Therefore, preventing p38 MAPK-mediated degradation of MafA represents a novel approach to improve beta-cell function.
278	19785038	We previously characterized human islet-derived precursor cells (hIPCs) as a specific type of mesenchymal stem cell capable of differentiating to insulin (INS)- and glucagon (GCG)-expressing cells.
279	19785038	We explored this possibility by determining whether ectopic expression of transcription factors known to induce transcription of this gene in beta cells, pancreatic and duodenal homeobox factor 1 (Pdx1), V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa), and neurogenic differentiation 1 (Neurod1), would activate INS gene expression in long-term hIPC cultures.
280	19785038	Coexpression of all three transcription factors had little effect on INS mRNA levels but unexpectedly increased GCG mRNA at least 100,000-fold.
281	19785038	In contrast to the endogenous promoter, an exogenous rat INS promoter was activated by expression of Pdx1 and Mafa in hIPCs.
282	19785038	Chromatin immunoprecipitation (ChIP) assays using antibodies directed at posttranslationally modified histones show that regions of the INS and GCG genes have similar levels of activation-associated modifications but the INS gene has higher levels of repression-associated modifications.
283	19785038	Furthermore, the INS gene was found to be less accessible to micrococcal nuclease digestion than the GCG gene.
284	19785038	Lastly, ChIP assays show that exogenously expressed Pdx1 and Mafa bind at very low levels to the INS promoter and at 20- to 25-fold higher levels to the GCG promoter in hIPCs.
285	19785038	We previously characterized human islet-derived precursor cells (hIPCs) as a specific type of mesenchymal stem cell capable of differentiating to insulin (INS)- and glucagon (GCG)-expressing cells.
286	19785038	We explored this possibility by determining whether ectopic expression of transcription factors known to induce transcription of this gene in beta cells, pancreatic and duodenal homeobox factor 1 (Pdx1), V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa), and neurogenic differentiation 1 (Neurod1), would activate INS gene expression in long-term hIPC cultures.
287	19785038	Coexpression of all three transcription factors had little effect on INS mRNA levels but unexpectedly increased GCG mRNA at least 100,000-fold.
288	19785038	In contrast to the endogenous promoter, an exogenous rat INS promoter was activated by expression of Pdx1 and Mafa in hIPCs.
289	19785038	Chromatin immunoprecipitation (ChIP) assays using antibodies directed at posttranslationally modified histones show that regions of the INS and GCG genes have similar levels of activation-associated modifications but the INS gene has higher levels of repression-associated modifications.
290	19785038	Furthermore, the INS gene was found to be less accessible to micrococcal nuclease digestion than the GCG gene.
291	19785038	Lastly, ChIP assays show that exogenously expressed Pdx1 and Mafa bind at very low levels to the INS promoter and at 20- to 25-fold higher levels to the GCG promoter in hIPCs.
292	19785038	We previously characterized human islet-derived precursor cells (hIPCs) as a specific type of mesenchymal stem cell capable of differentiating to insulin (INS)- and glucagon (GCG)-expressing cells.
293	19785038	We explored this possibility by determining whether ectopic expression of transcription factors known to induce transcription of this gene in beta cells, pancreatic and duodenal homeobox factor 1 (Pdx1), V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa), and neurogenic differentiation 1 (Neurod1), would activate INS gene expression in long-term hIPC cultures.
294	19785038	Coexpression of all three transcription factors had little effect on INS mRNA levels but unexpectedly increased GCG mRNA at least 100,000-fold.
295	19785038	In contrast to the endogenous promoter, an exogenous rat INS promoter was activated by expression of Pdx1 and Mafa in hIPCs.
296	19785038	Chromatin immunoprecipitation (ChIP) assays using antibodies directed at posttranslationally modified histones show that regions of the INS and GCG genes have similar levels of activation-associated modifications but the INS gene has higher levels of repression-associated modifications.
297	19785038	Furthermore, the INS gene was found to be less accessible to micrococcal nuclease digestion than the GCG gene.
298	19785038	Lastly, ChIP assays show that exogenously expressed Pdx1 and Mafa bind at very low levels to the INS promoter and at 20- to 25-fold higher levels to the GCG promoter in hIPCs.
299	19819955	Importantly, the loss of intranuclear musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) that was observed in nontransgenic db/db mice was prevented by GPx-1 overexpression, making this a likely mechanism for the improved glycemic control.
300	22150363	Reprogramming of pancreatic exocrine cells towards a beta (β) cell character using Pdx1, Ngn3 and MafA.
301	22150363	Pdx1 (pancreatic and duodenal homeobox 1), Ngn3 (neurogenin 3) and MafA (v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A) have been reported to bring about the transdifferentiation of pancreatic exocrine cells to beta (β) cells in vivo.
302	22150363	We constructed a new adenoviral vector encoding all three genes, called Ad-PNM (adenoviral Pdx1, Ngn3, MafA construct).
303	22150363	At the chromatin level, histone tail modifications of the Pdx1, Ins1 (insulin 1) and Ins2 (insulin 2) gene promoters are shifted in a direction associated with gene activity, and the level of DNA CpG methylation is reduced at the Ins1 promoter.
304	22150363	Reprogramming of pancreatic exocrine cells towards a beta (β) cell character using Pdx1, Ngn3 and MafA.
305	22150363	Pdx1 (pancreatic and duodenal homeobox 1), Ngn3 (neurogenin 3) and MafA (v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A) have been reported to bring about the transdifferentiation of pancreatic exocrine cells to beta (β) cells in vivo.
306	22150363	We constructed a new adenoviral vector encoding all three genes, called Ad-PNM (adenoviral Pdx1, Ngn3, MafA construct).
307	22150363	At the chromatin level, histone tail modifications of the Pdx1, Ins1 (insulin 1) and Ins2 (insulin 2) gene promoters are shifted in a direction associated with gene activity, and the level of DNA CpG methylation is reduced at the Ins1 promoter.
308	22150363	Reprogramming of pancreatic exocrine cells towards a beta (β) cell character using Pdx1, Ngn3 and MafA.
309	22150363	Pdx1 (pancreatic and duodenal homeobox 1), Ngn3 (neurogenin 3) and MafA (v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A) have been reported to bring about the transdifferentiation of pancreatic exocrine cells to beta (β) cells in vivo.
310	22150363	We constructed a new adenoviral vector encoding all three genes, called Ad-PNM (adenoviral Pdx1, Ngn3, MafA construct).
311	22150363	At the chromatin level, histone tail modifications of the Pdx1, Ins1 (insulin 1) and Ins2 (insulin 2) gene promoters are shifted in a direction associated with gene activity, and the level of DNA CpG methylation is reduced at the Ins1 promoter.
312	22685335	We used the hydrodynamic approach to deliver genes Pdx1, Ngn3 (Neurog3) and MafA singly and in combination to livers of normoglycaemic rats.
313	22685335	When Pdx1, Ngn3 and MafA were delivered together to normoglycaemic rats with these plasmids, insulin mRNA was detected at all time points and was ~50-fold higher with pCpG.
314	22761608	Combined transfection of the three transcriptional factors, PDX-1, NeuroD1, and MafA, causes differentiation of bone marrow mesenchymal stem cells into insulin-producing cells.
315	23610058	A protocol was developed whereby transduction of these mesenchymal cells with adenoviruses containing Pdx1, Ngn3, MafA, and Pax4 generated a population of cells that were enriched in glucagon-secreting α-like cells.
316	23610058	Transdifferentiation or reprogramming toward insulin-secreting β-cells was enhanced, however, when using unpassaged cells in combination with inhibition of EMT by inclusion of Rho-associated kinase (ROCK) and transforming growth factor-β1 inhibitors.
317	23624121	In this study, we established insulin-producing cells from bone marrow derived mesenchymal stem cells transiently expressing canine pancreatic and duodenal homeobox 1 (Pdx1), beta cell transactivator 2 (Beta2) and V-maf avian musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa) using a gene transfer technique.
318	23624121	These results suggest that co-transfection of Pdx1, Beta2 and Mafa induce insulin production in canine BMSCs.
319	23624121	In this study, we established insulin-producing cells from bone marrow derived mesenchymal stem cells transiently expressing canine pancreatic and duodenal homeobox 1 (Pdx1), beta cell transactivator 2 (Beta2) and V-maf avian musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa) using a gene transfer technique.
320	23624121	These results suggest that co-transfection of Pdx1, Beta2 and Mafa induce insulin production in canine BMSCs.
321	23736775	A Short-activating RNA Oligonucleotide Targeting the Islet β-cell Transcriptional Factor MafA in CD34(+) Cells.
322	23736775	We have developed a novel approach using short-activating RNA oligonucleotides to differentiate adult human CD34(+) cells into insulin-secreting cells.
323	23736775	By transfecting RNA to increase transcript levels of the master regulator of insulin biosynthesis, v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), several pancreatic endodermal genes were upregulated during the differentiation procedure.
324	23736775	These included Pancreatic and duodenal homeobox gene-1 (PDX1), Neurogenin 3, NeuroD, and NK6 homeobox 1 (NKx6-1).
325	23736775	Differentiated CD34(+) cells also expressed glucokinase, glucagon-like peptide 1 receptor (GLP1R), sulfonylurea receptor-1 (SUR1) and phogrin-all essential for glucose sensitivity and insulin secretion.
326	23736775	A Short-activating RNA Oligonucleotide Targeting the Islet β-cell Transcriptional Factor MafA in CD34(+) Cells.
327	23736775	We have developed a novel approach using short-activating RNA oligonucleotides to differentiate adult human CD34(+) cells into insulin-secreting cells.
328	23736775	By transfecting RNA to increase transcript levels of the master regulator of insulin biosynthesis, v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), several pancreatic endodermal genes were upregulated during the differentiation procedure.
329	23736775	These included Pancreatic and duodenal homeobox gene-1 (PDX1), Neurogenin 3, NeuroD, and NK6 homeobox 1 (NKx6-1).
330	23736775	Differentiated CD34(+) cells also expressed glucokinase, glucagon-like peptide 1 receptor (GLP1R), sulfonylurea receptor-1 (SUR1) and phogrin-all essential for glucose sensitivity and insulin secretion.
331	23927931	The Krüppel-like protein Gli-similar 3 (Glis3) functions as a key regulator of insulin transcription.
332	23927931	Recently, the Krüppel-like transcription factor, Gli-similar 3 (Glis3), was shown to bind the insulin (INS) promoter and positively influence insulin transcription.
333	23927931	In this report, we examined in detail the synergistic activation of insulin transcription by Glis3 with coregulators, CREB-binding protein (CBP)/p300, pancreatic and duodenal homeobox 1 (Pdx1), neuronal differentiation 1 (NeuroD1), and v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA).
334	23927931	Our data show that Glis3 expression, the binding of Glis3 to GlisBS, and its recruitment of CBP are required for optimal activation of the insulin promoter in pancreatic β-cells not only by Glis3, but also by Pdx1, MafA, and NeuroD1.
335	23927931	Mutations in the GlisBS or small interfering RNA-directed knockdown of GLIS3 diminished insulin promoter activation by Pdx1, NeuroD1, and MafA, and neither Pdx1 nor MafA was able to stably associate with the insulin promoter when the GlisBS were mutated.
336	23927931	In addition, a GlisBS mutation in the INS promoter implicated in the development of neonatal diabetes similarly abated activation by Pdx1, NeuroD1, and MafA that could be reversed by increased expression of exogenous Glis3.
337	23927931	We therefore propose that recruitment of CBP/p300 by Glis3 provides a scaffold for the formation of a larger transcriptional regulatory complex that stabilizes the binding of Pdx1, NeuroD1, and MafA complexes to their respective binding sites within the insulin promoter.
338	23927931	Taken together, these results indicate that Glis3 plays a pivotal role in the transcriptional regulation of insulin and may serve as an important therapeutic target for the treatment of diabetes.
339	23927931	The Krüppel-like protein Gli-similar 3 (Glis3) functions as a key regulator of insulin transcription.
340	23927931	Recently, the Krüppel-like transcription factor, Gli-similar 3 (Glis3), was shown to bind the insulin (INS) promoter and positively influence insulin transcription.
341	23927931	In this report, we examined in detail the synergistic activation of insulin transcription by Glis3 with coregulators, CREB-binding protein (CBP)/p300, pancreatic and duodenal homeobox 1 (Pdx1), neuronal differentiation 1 (NeuroD1), and v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA).
342	23927931	Our data show that Glis3 expression, the binding of Glis3 to GlisBS, and its recruitment of CBP are required for optimal activation of the insulin promoter in pancreatic β-cells not only by Glis3, but also by Pdx1, MafA, and NeuroD1.
343	23927931	Mutations in the GlisBS or small interfering RNA-directed knockdown of GLIS3 diminished insulin promoter activation by Pdx1, NeuroD1, and MafA, and neither Pdx1 nor MafA was able to stably associate with the insulin promoter when the GlisBS were mutated.
344	23927931	In addition, a GlisBS mutation in the INS promoter implicated in the development of neonatal diabetes similarly abated activation by Pdx1, NeuroD1, and MafA that could be reversed by increased expression of exogenous Glis3.
345	23927931	We therefore propose that recruitment of CBP/p300 by Glis3 provides a scaffold for the formation of a larger transcriptional regulatory complex that stabilizes the binding of Pdx1, NeuroD1, and MafA complexes to their respective binding sites within the insulin promoter.
346	23927931	Taken together, these results indicate that Glis3 plays a pivotal role in the transcriptional regulation of insulin and may serve as an important therapeutic target for the treatment of diabetes.
347	23927931	The Krüppel-like protein Gli-similar 3 (Glis3) functions as a key regulator of insulin transcription.
348	23927931	Recently, the Krüppel-like transcription factor, Gli-similar 3 (Glis3), was shown to bind the insulin (INS) promoter and positively influence insulin transcription.
349	23927931	In this report, we examined in detail the synergistic activation of insulin transcription by Glis3 with coregulators, CREB-binding protein (CBP)/p300, pancreatic and duodenal homeobox 1 (Pdx1), neuronal differentiation 1 (NeuroD1), and v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA).
350	23927931	Our data show that Glis3 expression, the binding of Glis3 to GlisBS, and its recruitment of CBP are required for optimal activation of the insulin promoter in pancreatic β-cells not only by Glis3, but also by Pdx1, MafA, and NeuroD1.
351	23927931	Mutations in the GlisBS or small interfering RNA-directed knockdown of GLIS3 diminished insulin promoter activation by Pdx1, NeuroD1, and MafA, and neither Pdx1 nor MafA was able to stably associate with the insulin promoter when the GlisBS were mutated.
352	23927931	In addition, a GlisBS mutation in the INS promoter implicated in the development of neonatal diabetes similarly abated activation by Pdx1, NeuroD1, and MafA that could be reversed by increased expression of exogenous Glis3.
353	23927931	We therefore propose that recruitment of CBP/p300 by Glis3 provides a scaffold for the formation of a larger transcriptional regulatory complex that stabilizes the binding of Pdx1, NeuroD1, and MafA complexes to their respective binding sites within the insulin promoter.
354	23927931	Taken together, these results indicate that Glis3 plays a pivotal role in the transcriptional regulation of insulin and may serve as an important therapeutic target for the treatment of diabetes.
355	23927931	The Krüppel-like protein Gli-similar 3 (Glis3) functions as a key regulator of insulin transcription.
356	23927931	Recently, the Krüppel-like transcription factor, Gli-similar 3 (Glis3), was shown to bind the insulin (INS) promoter and positively influence insulin transcription.
357	23927931	In this report, we examined in detail the synergistic activation of insulin transcription by Glis3 with coregulators, CREB-binding protein (CBP)/p300, pancreatic and duodenal homeobox 1 (Pdx1), neuronal differentiation 1 (NeuroD1), and v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA).
358	23927931	Our data show that Glis3 expression, the binding of Glis3 to GlisBS, and its recruitment of CBP are required for optimal activation of the insulin promoter in pancreatic β-cells not only by Glis3, but also by Pdx1, MafA, and NeuroD1.
359	23927931	Mutations in the GlisBS or small interfering RNA-directed knockdown of GLIS3 diminished insulin promoter activation by Pdx1, NeuroD1, and MafA, and neither Pdx1 nor MafA was able to stably associate with the insulin promoter when the GlisBS were mutated.
360	23927931	In addition, a GlisBS mutation in the INS promoter implicated in the development of neonatal diabetes similarly abated activation by Pdx1, NeuroD1, and MafA that could be reversed by increased expression of exogenous Glis3.
361	23927931	We therefore propose that recruitment of CBP/p300 by Glis3 provides a scaffold for the formation of a larger transcriptional regulatory complex that stabilizes the binding of Pdx1, NeuroD1, and MafA complexes to their respective binding sites within the insulin promoter.
362	23927931	Taken together, these results indicate that Glis3 plays a pivotal role in the transcriptional regulation of insulin and may serve as an important therapeutic target for the treatment of diabetes.
363	23927931	The Krüppel-like protein Gli-similar 3 (Glis3) functions as a key regulator of insulin transcription.
364	23927931	Recently, the Krüppel-like transcription factor, Gli-similar 3 (Glis3), was shown to bind the insulin (INS) promoter and positively influence insulin transcription.
365	23927931	In this report, we examined in detail the synergistic activation of insulin transcription by Glis3 with coregulators, CREB-binding protein (CBP)/p300, pancreatic and duodenal homeobox 1 (Pdx1), neuronal differentiation 1 (NeuroD1), and v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA).
366	23927931	Our data show that Glis3 expression, the binding of Glis3 to GlisBS, and its recruitment of CBP are required for optimal activation of the insulin promoter in pancreatic β-cells not only by Glis3, but also by Pdx1, MafA, and NeuroD1.
367	23927931	Mutations in the GlisBS or small interfering RNA-directed knockdown of GLIS3 diminished insulin promoter activation by Pdx1, NeuroD1, and MafA, and neither Pdx1 nor MafA was able to stably associate with the insulin promoter when the GlisBS were mutated.
368	23927931	In addition, a GlisBS mutation in the INS promoter implicated in the development of neonatal diabetes similarly abated activation by Pdx1, NeuroD1, and MafA that could be reversed by increased expression of exogenous Glis3.
369	23927931	We therefore propose that recruitment of CBP/p300 by Glis3 provides a scaffold for the formation of a larger transcriptional regulatory complex that stabilizes the binding of Pdx1, NeuroD1, and MafA complexes to their respective binding sites within the insulin promoter.
370	23927931	Taken together, these results indicate that Glis3 plays a pivotal role in the transcriptional regulation of insulin and may serve as an important therapeutic target for the treatment of diabetes.
371	24013263	Both PAX4 and MAFA are expressed in a substantial proportion of normal human pancreatic alpha cells and deregulated in patients with type 2 diabetes.
372	24013263	Pax4 and MafA (v-maf musculoaponeurotic fibrosarcoma oncogene homolog A) are two transcription factors crucial for normal functions of islet beta cells in the mouse.
373	24013263	To better understand the biological role of human PAX4 and MAFA, we investigated their expression in normal and diseased human islets, using validated antibodies.
374	24013263	We found that MAFA, detected in 88.3±6.3% insulin(+)cells as in the mouse, turned out to be also expressed in 61.2±6.4% of human glucagons(+) cells with less intensity than in insulin(+) cells, whereas MAFB expression was found not only in the majority of glucagon(+) cells (67.2±7.6%), but also in 53.6±10.5% of human insulin(+) cells.
375	24013263	Both MAFA and PAX4 display, therefore, a distinct expression pattern in human islet cells, suggesting more potential plasticity of human islets as compared with rodent islets.
376	24013263	Both PAX4 and MAFA are expressed in a substantial proportion of normal human pancreatic alpha cells and deregulated in patients with type 2 diabetes.
377	24013263	Pax4 and MafA (v-maf musculoaponeurotic fibrosarcoma oncogene homolog A) are two transcription factors crucial for normal functions of islet beta cells in the mouse.
378	24013263	To better understand the biological role of human PAX4 and MAFA, we investigated their expression in normal and diseased human islets, using validated antibodies.
379	24013263	We found that MAFA, detected in 88.3±6.3% insulin(+)cells as in the mouse, turned out to be also expressed in 61.2±6.4% of human glucagons(+) cells with less intensity than in insulin(+) cells, whereas MAFB expression was found not only in the majority of glucagon(+) cells (67.2±7.6%), but also in 53.6±10.5% of human insulin(+) cells.
380	24013263	Both MAFA and PAX4 display, therefore, a distinct expression pattern in human islet cells, suggesting more potential plasticity of human islets as compared with rodent islets.
381	24013263	Both PAX4 and MAFA are expressed in a substantial proportion of normal human pancreatic alpha cells and deregulated in patients with type 2 diabetes.
382	24013263	Pax4 and MafA (v-maf musculoaponeurotic fibrosarcoma oncogene homolog A) are two transcription factors crucial for normal functions of islet beta cells in the mouse.
383	24013263	To better understand the biological role of human PAX4 and MAFA, we investigated their expression in normal and diseased human islets, using validated antibodies.
384	24013263	We found that MAFA, detected in 88.3±6.3% insulin(+)cells as in the mouse, turned out to be also expressed in 61.2±6.4% of human glucagons(+) cells with less intensity than in insulin(+) cells, whereas MAFB expression was found not only in the majority of glucagon(+) cells (67.2±7.6%), but also in 53.6±10.5% of human insulin(+) cells.
385	24013263	Both MAFA and PAX4 display, therefore, a distinct expression pattern in human islet cells, suggesting more potential plasticity of human islets as compared with rodent islets.
386	24013263	Both PAX4 and MAFA are expressed in a substantial proportion of normal human pancreatic alpha cells and deregulated in patients with type 2 diabetes.
387	24013263	Pax4 and MafA (v-maf musculoaponeurotic fibrosarcoma oncogene homolog A) are two transcription factors crucial for normal functions of islet beta cells in the mouse.
388	24013263	To better understand the biological role of human PAX4 and MAFA, we investigated their expression in normal and diseased human islets, using validated antibodies.
389	24013263	We found that MAFA, detected in 88.3±6.3% insulin(+)cells as in the mouse, turned out to be also expressed in 61.2±6.4% of human glucagons(+) cells with less intensity than in insulin(+) cells, whereas MAFB expression was found not only in the majority of glucagon(+) cells (67.2±7.6%), but also in 53.6±10.5% of human insulin(+) cells.
390	24013263	Both MAFA and PAX4 display, therefore, a distinct expression pattern in human islet cells, suggesting more potential plasticity of human islets as compared with rodent islets.
391	24013263	Both PAX4 and MAFA are expressed in a substantial proportion of normal human pancreatic alpha cells and deregulated in patients with type 2 diabetes.
392	24013263	Pax4 and MafA (v-maf musculoaponeurotic fibrosarcoma oncogene homolog A) are two transcription factors crucial for normal functions of islet beta cells in the mouse.
393	24013263	To better understand the biological role of human PAX4 and MAFA, we investigated their expression in normal and diseased human islets, using validated antibodies.
394	24013263	We found that MAFA, detected in 88.3±6.3% insulin(+)cells as in the mouse, turned out to be also expressed in 61.2±6.4% of human glucagons(+) cells with less intensity than in insulin(+) cells, whereas MAFB expression was found not only in the majority of glucagon(+) cells (67.2±7.6%), but also in 53.6±10.5% of human insulin(+) cells.
395	24013263	Both MAFA and PAX4 display, therefore, a distinct expression pattern in human islet cells, suggesting more potential plasticity of human islets as compared with rodent islets.