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Gene Information
Gene symbol: PDX1
Gene name: pancreatic and duodenal homeobox 1
HGNC ID: 6107
Synonyms: IDX-1, STF-1, PDX-1, MODY4
Related Genes
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 | 8866550 | The human glucokinase gene beta-cell-type promoter: an essential role of insulin promoter factor 1/PDX-1 in its activation in HIT-T15 cells. |
| 14 | 8866550 | The glycolytic enzyme glucokinase plays a primary role in the glucose-responsive secretion of insulin, and defects of this enzyme can cause NIDDM. |
| 15 | 8866550 | In contrast to the insulin gene, however, neither the synergistic effect of the Pan1 expression on the IPF1-induced promoter activation nor the glucose responsiveness of the activity was observed for the GK gene promoter. |
| 16 | 8866550 | Being implicated in insulin and GK gene regulations as a common transcription factor, IPF1/STF-1/PDX-1 is likely to play an essential role in maintaining normal beta-cell functions. |
| 17 | 8866550 | The human glucokinase gene beta-cell-type promoter: an essential role of insulin promoter factor 1/PDX-1 in its activation in HIT-T15 cells. |
| 18 | 8866550 | The glycolytic enzyme glucokinase plays a primary role in the glucose-responsive secretion of insulin, and defects of this enzyme can cause NIDDM. |
| 19 | 8866550 | In contrast to the insulin gene, however, neither the synergistic effect of the Pan1 expression on the IPF1-induced promoter activation nor the glucose responsiveness of the activity was observed for the GK gene promoter. |
| 20 | 8866550 | Being implicated in insulin and GK gene regulations as a common transcription factor, IPF1/STF-1/PDX-1 is likely to play an essential role in maintaining normal beta-cell functions. |
| 21 | 8866550 | The human glucokinase gene beta-cell-type promoter: an essential role of insulin promoter factor 1/PDX-1 in its activation in HIT-T15 cells. |
| 22 | 8866550 | The glycolytic enzyme glucokinase plays a primary role in the glucose-responsive secretion of insulin, and defects of this enzyme can cause NIDDM. |
| 23 | 8866550 | In contrast to the insulin gene, however, neither the synergistic effect of the Pan1 expression on the IPF1-induced promoter activation nor the glucose responsiveness of the activity was observed for the GK gene promoter. |
| 24 | 8866550 | Being implicated in insulin and GK gene regulations as a common transcription factor, IPF1/STF-1/PDX-1 is likely to play an essential role in maintaining normal beta-cell functions. |
| 25 | 8922372 | PDX-1 induces insulin and glucokinase gene expressions in alphaTC1 clone 6 cells in the presence of betacellulin. |
| 26 | 8922372 | Among the two important transcription factors for insulin gene expression, IEF1 is present both in alpha- and beta-cells, but PDX-1/IPF1/STF-1/IDX-1, a homeodomain-containing transcription factor, is present in beta-cells but not in alpha-cells. |
| 27 | 8922372 | The exogenous expression of PDX-1 in alphaTC1.6 cells alone could induce islet amyloid polypeptide (IAPP) mRNA expression in the cells but not the expression of insulin, glucokinase, or GLUT2 gene. |
| 28 | 8922372 | However, when betacellulin was added to the medium, the PDX-1-expressing alphaTC1.6 cells, but not the control alphaTC1.6 cells, came to express insulin and glucokinase mRNAs. |
| 29 | 8922372 | This did not occur with other growth factors such as epidermal growth factor, transforming growth factor alpha, and insulin-like growth factor I. |
| 30 | 8922372 | GLUT2 mRNA remained undetectable in the PDX-1--expressing alphaTC1.6 cells. |
| 31 | 8922372 | These observations demonstrate the potency of PDX-1 for the expression of the insulin, glucokinase, and IAPP genes and suggest that certain regulatory factors, which can partially be modified by betacellulin, also contribute to the beta-cell specificity of gene expression. |
| 32 | 8922372 | PDX-1 induces insulin and glucokinase gene expressions in alphaTC1 clone 6 cells in the presence of betacellulin. |
| 33 | 8922372 | Among the two important transcription factors for insulin gene expression, IEF1 is present both in alpha- and beta-cells, but PDX-1/IPF1/STF-1/IDX-1, a homeodomain-containing transcription factor, is present in beta-cells but not in alpha-cells. |
| 34 | 8922372 | The exogenous expression of PDX-1 in alphaTC1.6 cells alone could induce islet amyloid polypeptide (IAPP) mRNA expression in the cells but not the expression of insulin, glucokinase, or GLUT2 gene. |
| 35 | 8922372 | However, when betacellulin was added to the medium, the PDX-1-expressing alphaTC1.6 cells, but not the control alphaTC1.6 cells, came to express insulin and glucokinase mRNAs. |
| 36 | 8922372 | This did not occur with other growth factors such as epidermal growth factor, transforming growth factor alpha, and insulin-like growth factor I. |
| 37 | 8922372 | GLUT2 mRNA remained undetectable in the PDX-1--expressing alphaTC1.6 cells. |
| 38 | 8922372 | These observations demonstrate the potency of PDX-1 for the expression of the insulin, glucokinase, and IAPP genes and suggest that certain regulatory factors, which can partially be modified by betacellulin, also contribute to the beta-cell specificity of gene expression. |
| 39 | 8922372 | PDX-1 induces insulin and glucokinase gene expressions in alphaTC1 clone 6 cells in the presence of betacellulin. |
| 40 | 8922372 | Among the two important transcription factors for insulin gene expression, IEF1 is present both in alpha- and beta-cells, but PDX-1/IPF1/STF-1/IDX-1, a homeodomain-containing transcription factor, is present in beta-cells but not in alpha-cells. |
| 41 | 8922372 | The exogenous expression of PDX-1 in alphaTC1.6 cells alone could induce islet amyloid polypeptide (IAPP) mRNA expression in the cells but not the expression of insulin, glucokinase, or GLUT2 gene. |
| 42 | 8922372 | However, when betacellulin was added to the medium, the PDX-1-expressing alphaTC1.6 cells, but not the control alphaTC1.6 cells, came to express insulin and glucokinase mRNAs. |
| 43 | 8922372 | This did not occur with other growth factors such as epidermal growth factor, transforming growth factor alpha, and insulin-like growth factor I. |
| 44 | 8922372 | GLUT2 mRNA remained undetectable in the PDX-1--expressing alphaTC1.6 cells. |
| 45 | 8922372 | These observations demonstrate the potency of PDX-1 for the expression of the insulin, glucokinase, and IAPP genes and suggest that certain regulatory factors, which can partially be modified by betacellulin, also contribute to the beta-cell specificity of gene expression. |
| 46 | 8922372 | PDX-1 induces insulin and glucokinase gene expressions in alphaTC1 clone 6 cells in the presence of betacellulin. |
| 47 | 8922372 | Among the two important transcription factors for insulin gene expression, IEF1 is present both in alpha- and beta-cells, but PDX-1/IPF1/STF-1/IDX-1, a homeodomain-containing transcription factor, is present in beta-cells but not in alpha-cells. |
| 48 | 8922372 | The exogenous expression of PDX-1 in alphaTC1.6 cells alone could induce islet amyloid polypeptide (IAPP) mRNA expression in the cells but not the expression of insulin, glucokinase, or GLUT2 gene. |
| 49 | 8922372 | However, when betacellulin was added to the medium, the PDX-1-expressing alphaTC1.6 cells, but not the control alphaTC1.6 cells, came to express insulin and glucokinase mRNAs. |
| 50 | 8922372 | This did not occur with other growth factors such as epidermal growth factor, transforming growth factor alpha, and insulin-like growth factor I. |
| 51 | 8922372 | GLUT2 mRNA remained undetectable in the PDX-1--expressing alphaTC1.6 cells. |
| 52 | 8922372 | These observations demonstrate the potency of PDX-1 for the expression of the insulin, glucokinase, and IAPP genes and suggest that certain regulatory factors, which can partially be modified by betacellulin, also contribute to the beta-cell specificity of gene expression. |
| 53 | 8922372 | PDX-1 induces insulin and glucokinase gene expressions in alphaTC1 clone 6 cells in the presence of betacellulin. |
| 54 | 8922372 | Among the two important transcription factors for insulin gene expression, IEF1 is present both in alpha- and beta-cells, but PDX-1/IPF1/STF-1/IDX-1, a homeodomain-containing transcription factor, is present in beta-cells but not in alpha-cells. |
| 55 | 8922372 | The exogenous expression of PDX-1 in alphaTC1.6 cells alone could induce islet amyloid polypeptide (IAPP) mRNA expression in the cells but not the expression of insulin, glucokinase, or GLUT2 gene. |
| 56 | 8922372 | However, when betacellulin was added to the medium, the PDX-1-expressing alphaTC1.6 cells, but not the control alphaTC1.6 cells, came to express insulin and glucokinase mRNAs. |
| 57 | 8922372 | This did not occur with other growth factors such as epidermal growth factor, transforming growth factor alpha, and insulin-like growth factor I. |
| 58 | 8922372 | GLUT2 mRNA remained undetectable in the PDX-1--expressing alphaTC1.6 cells. |
| 59 | 8922372 | These observations demonstrate the potency of PDX-1 for the expression of the insulin, glucokinase, and IAPP genes and suggest that certain regulatory factors, which can partially be modified by betacellulin, also contribute to the beta-cell specificity of gene expression. |
| 60 | 8922372 | PDX-1 induces insulin and glucokinase gene expressions in alphaTC1 clone 6 cells in the presence of betacellulin. |
| 61 | 8922372 | Among the two important transcription factors for insulin gene expression, IEF1 is present both in alpha- and beta-cells, but PDX-1/IPF1/STF-1/IDX-1, a homeodomain-containing transcription factor, is present in beta-cells but not in alpha-cells. |
| 62 | 8922372 | The exogenous expression of PDX-1 in alphaTC1.6 cells alone could induce islet amyloid polypeptide (IAPP) mRNA expression in the cells but not the expression of insulin, glucokinase, or GLUT2 gene. |
| 63 | 8922372 | However, when betacellulin was added to the medium, the PDX-1-expressing alphaTC1.6 cells, but not the control alphaTC1.6 cells, came to express insulin and glucokinase mRNAs. |
| 64 | 8922372 | This did not occur with other growth factors such as epidermal growth factor, transforming growth factor alpha, and insulin-like growth factor I. |
| 65 | 8922372 | GLUT2 mRNA remained undetectable in the PDX-1--expressing alphaTC1.6 cells. |
| 66 | 8922372 | These observations demonstrate the potency of PDX-1 for the expression of the insulin, glucokinase, and IAPP genes and suggest that certain regulatory factors, which can partially be modified by betacellulin, also contribute to the beta-cell specificity of gene expression. |
| 67 | 8923459 | Transcriptional activation of the GLUT2 gene by the IPF-1/STF-1/IDX-1 homeobox factor. |
| 68 | 8923459 | As the glucose transporter type 2 (GLUT2) gene expression is selectively decreased in the beta-pancreatic cells of experimental models of diabetes, we postulated that the loss of GLUT2 gene expression in the pancreatic islets of diabetic animals may be due to the loss of PDX-1 transacting function on the GLUT2 gene. |
| 69 | 8923459 | We, therefore, investigated the potential role of PDX-1 in the transcriptional control of GLUT2. |
| 70 | 8923459 | PDX-1 antiserum detects the formation of the complex of PDX-1 with the GLUT2TAAT motif in nuclear extracts from the pancreatic insulin-secreting cell line, beta TC3. |
| 71 | 8923459 | These data demonstrate that the murine GLUT2 promoter is controlled by the PDX-1 homeobox factor through the identified GLUT2TAAT motif. |
| 72 | 8923459 | Transcriptional activation of the GLUT2 gene by the IPF-1/STF-1/IDX-1 homeobox factor. |
| 73 | 8923459 | As the glucose transporter type 2 (GLUT2) gene expression is selectively decreased in the beta-pancreatic cells of experimental models of diabetes, we postulated that the loss of GLUT2 gene expression in the pancreatic islets of diabetic animals may be due to the loss of PDX-1 transacting function on the GLUT2 gene. |
| 74 | 8923459 | We, therefore, investigated the potential role of PDX-1 in the transcriptional control of GLUT2. |
| 75 | 8923459 | PDX-1 antiserum detects the formation of the complex of PDX-1 with the GLUT2TAAT motif in nuclear extracts from the pancreatic insulin-secreting cell line, beta TC3. |
| 76 | 8923459 | These data demonstrate that the murine GLUT2 promoter is controlled by the PDX-1 homeobox factor through the identified GLUT2TAAT motif. |
| 77 | 8923459 | Transcriptional activation of the GLUT2 gene by the IPF-1/STF-1/IDX-1 homeobox factor. |
| 78 | 8923459 | As the glucose transporter type 2 (GLUT2) gene expression is selectively decreased in the beta-pancreatic cells of experimental models of diabetes, we postulated that the loss of GLUT2 gene expression in the pancreatic islets of diabetic animals may be due to the loss of PDX-1 transacting function on the GLUT2 gene. |
| 79 | 8923459 | We, therefore, investigated the potential role of PDX-1 in the transcriptional control of GLUT2. |
| 80 | 8923459 | PDX-1 antiserum detects the formation of the complex of PDX-1 with the GLUT2TAAT motif in nuclear extracts from the pancreatic insulin-secreting cell line, beta TC3. |
| 81 | 8923459 | These data demonstrate that the murine GLUT2 promoter is controlled by the PDX-1 homeobox factor through the identified GLUT2TAAT motif. |
| 82 | 8923459 | Transcriptional activation of the GLUT2 gene by the IPF-1/STF-1/IDX-1 homeobox factor. |
| 83 | 8923459 | As the glucose transporter type 2 (GLUT2) gene expression is selectively decreased in the beta-pancreatic cells of experimental models of diabetes, we postulated that the loss of GLUT2 gene expression in the pancreatic islets of diabetic animals may be due to the loss of PDX-1 transacting function on the GLUT2 gene. |
| 84 | 8923459 | We, therefore, investigated the potential role of PDX-1 in the transcriptional control of GLUT2. |
| 85 | 8923459 | PDX-1 antiserum detects the formation of the complex of PDX-1 with the GLUT2TAAT motif in nuclear extracts from the pancreatic insulin-secreting cell line, beta TC3. |
| 86 | 8923459 | These data demonstrate that the murine GLUT2 promoter is controlled by the PDX-1 homeobox factor through the identified GLUT2TAAT motif. |
| 87 | 8923459 | Transcriptional activation of the GLUT2 gene by the IPF-1/STF-1/IDX-1 homeobox factor. |
| 88 | 8923459 | As the glucose transporter type 2 (GLUT2) gene expression is selectively decreased in the beta-pancreatic cells of experimental models of diabetes, we postulated that the loss of GLUT2 gene expression in the pancreatic islets of diabetic animals may be due to the loss of PDX-1 transacting function on the GLUT2 gene. |
| 89 | 8923459 | We, therefore, investigated the potential role of PDX-1 in the transcriptional control of GLUT2. |
| 90 | 8923459 | PDX-1 antiserum detects the formation of the complex of PDX-1 with the GLUT2TAAT motif in nuclear extracts from the pancreatic insulin-secreting cell line, beta TC3. |
| 91 | 8923459 | These data demonstrate that the murine GLUT2 promoter is controlled by the PDX-1 homeobox factor through the identified GLUT2TAAT motif. |
| 92 | 9000703 | Reduced insulin, GLUT2, and IDX-1 in beta-cells after partial pancreatectomy. |
| 93 | 9000703 | Reduction of GLUT2 is associated with loss of glucose-induced insulin secretion in genetic and chemical diabetes and in transplanted islets exposed to chronic hyperglycemia. |
| 94 | 9000703 | Islet GLUT2 and insulin mRNA were measured with quantitative reverse transcriptase-polymerase chain reaction. |
| 95 | 9000703 | These data suggest that 1) the loss of GLUT2 protein associated with hyperglycemia is at least partially explained by reduced levels of the GLUT2 gene transcripts; 2) the reduction of beta-cell insulin content during chronic hyperglycemia may not be completely due to degranulation (reduced levels of gene transcripts may play a role); and 3) the reduction in the transcription factor IDX-1 raises the possibility that dysregulation of transcription factors may contribute to the abnormal beta-cell function found in states of chronic hyperglycemia. |
| 96 | 9000703 | Reduced insulin, GLUT2, and IDX-1 in beta-cells after partial pancreatectomy. |
| 97 | 9000703 | Reduction of GLUT2 is associated with loss of glucose-induced insulin secretion in genetic and chemical diabetes and in transplanted islets exposed to chronic hyperglycemia. |
| 98 | 9000703 | Islet GLUT2 and insulin mRNA were measured with quantitative reverse transcriptase-polymerase chain reaction. |
| 99 | 9000703 | These data suggest that 1) the loss of GLUT2 protein associated with hyperglycemia is at least partially explained by reduced levels of the GLUT2 gene transcripts; 2) the reduction of beta-cell insulin content during chronic hyperglycemia may not be completely due to degranulation (reduced levels of gene transcripts may play a role); and 3) the reduction in the transcription factor IDX-1 raises the possibility that dysregulation of transcription factors may contribute to the abnormal beta-cell function found in states of chronic hyperglycemia. |
| 100 | 9011569 | The results of reporter gene analyses revealed that the insulin gene promoter is more sensitive to glycation than the control beta-actin gene promoter; approximately 50 and 80% of the insulin gene promoter activity was lost when the cells were kept for 3 d in the presence of 40 and 60 mM D-ribose, respectively. |
| 101 | 9011569 | Also, gel mobility shift analyses using specific antiserum revealed decrease in the DNA-binding activity of an insulin gene transcription factor, PDX-1/IPF1/STF-1. |
| 102 | 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. |
| 103 | 9022089 | They regained binding of STF-1 and RIPE-3b1 activator and had a partial but minimal return of insulin mRNA expression. |
| 104 | 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. |
| 105 | 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. |
| 106 | 9022089 | They regained binding of STF-1 and RIPE-3b1 activator and had a partial but minimal return of insulin mRNA expression. |
| 107 | 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. |
| 108 | 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. |
| 109 | 9022089 | They regained binding of STF-1 and RIPE-3b1 activator and had a partial but minimal return of insulin mRNA expression. |
| 110 | 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. |
| 111 | 9075740 | After SZ-mediated elimination of existing IN+/PDX-1+ cells, a population of somatostatin (SOM)+/PDX-1+ cells, a cell type thought to represent an embryonic islet precursor cell, appeared in islets. |
| 112 | 9075740 | The appearance of SOM+/PDX-1+ cells was followed in time by the differentiation to SOM+/IN+/PDX-1+ cells. |
| 113 | 9075740 | SOM+/PDX-1+ cells also appeared in islets of nonobese diabetic mice, a strain of mice in which beta cell destruction is immune-mediated. |
| 114 | 9075740 | After SZ-mediated elimination of existing IN+/PDX-1+ cells, a population of somatostatin (SOM)+/PDX-1+ cells, a cell type thought to represent an embryonic islet precursor cell, appeared in islets. |
| 115 | 9075740 | The appearance of SOM+/PDX-1+ cells was followed in time by the differentiation to SOM+/IN+/PDX-1+ cells. |
| 116 | 9075740 | SOM+/PDX-1+ cells also appeared in islets of nonobese diabetic mice, a strain of mice in which beta cell destruction is immune-mediated. |
| 117 | 9075740 | After SZ-mediated elimination of existing IN+/PDX-1+ cells, a population of somatostatin (SOM)+/PDX-1+ cells, a cell type thought to represent an embryonic islet precursor cell, appeared in islets. |
| 118 | 9075740 | The appearance of SOM+/PDX-1+ cells was followed in time by the differentiation to SOM+/IN+/PDX-1+ cells. |
| 119 | 9075740 | SOM+/PDX-1+ cells also appeared in islets of nonobese diabetic mice, a strain of mice in which beta cell destruction is immune-mediated. |
| 120 | 9181474 | The homeodomain protein PDX-1, an insulin gene transcription factor, is uniformly expressed in the early pancreatic bud, and null mutation of PDX-1 in mice results in a failure of the pancreatic bud to grow and differentiate. |
| 121 | 9453241 | The transcriptional control of the gene in beta-cells involves at least two islet-specific DNA-binding proteins, GTIIa and PDX-1, which also transactivates the insulin, somatostatin and glucokinase genes. |
| 122 | 9453241 | In this report, we assessed the DNA-binding activities of GTIIa and PDX-1 to their respective cis-elements of the GLUT2 promoter using nuclear extracts prepared from pancreatic islets of 12 week old db/db diabetic mice. |
| 123 | 9453241 | We show that the decreased GLUT2 mRNA expression correlates with a decrease of the GTIIa DNA-binding activity, whereas the PDX-1 binding activity is increased. |
| 124 | 9453241 | The adjunction of dexamethasone to isolated pancreatic islets, a treatment previously shown to decrease PDX-1 expression in the insulin-secreting HIT-T15 cells, has no effect on the GTIIa and PDX-1 DNA-binding activities. |
| 125 | 9453241 | The transcriptional control of the gene in beta-cells involves at least two islet-specific DNA-binding proteins, GTIIa and PDX-1, which also transactivates the insulin, somatostatin and glucokinase genes. |
| 126 | 9453241 | In this report, we assessed the DNA-binding activities of GTIIa and PDX-1 to their respective cis-elements of the GLUT2 promoter using nuclear extracts prepared from pancreatic islets of 12 week old db/db diabetic mice. |
| 127 | 9453241 | We show that the decreased GLUT2 mRNA expression correlates with a decrease of the GTIIa DNA-binding activity, whereas the PDX-1 binding activity is increased. |
| 128 | 9453241 | The adjunction of dexamethasone to isolated pancreatic islets, a treatment previously shown to decrease PDX-1 expression in the insulin-secreting HIT-T15 cells, has no effect on the GTIIa and PDX-1 DNA-binding activities. |
| 129 | 9453241 | The transcriptional control of the gene in beta-cells involves at least two islet-specific DNA-binding proteins, GTIIa and PDX-1, which also transactivates the insulin, somatostatin and glucokinase genes. |
| 130 | 9453241 | In this report, we assessed the DNA-binding activities of GTIIa and PDX-1 to their respective cis-elements of the GLUT2 promoter using nuclear extracts prepared from pancreatic islets of 12 week old db/db diabetic mice. |
| 131 | 9453241 | We show that the decreased GLUT2 mRNA expression correlates with a decrease of the GTIIa DNA-binding activity, whereas the PDX-1 binding activity is increased. |
| 132 | 9453241 | The adjunction of dexamethasone to isolated pancreatic islets, a treatment previously shown to decrease PDX-1 expression in the insulin-secreting HIT-T15 cells, has no effect on the GTIIa and PDX-1 DNA-binding activities. |
| 133 | 9453241 | The transcriptional control of the gene in beta-cells involves at least two islet-specific DNA-binding proteins, GTIIa and PDX-1, which also transactivates the insulin, somatostatin and glucokinase genes. |
| 134 | 9453241 | In this report, we assessed the DNA-binding activities of GTIIa and PDX-1 to their respective cis-elements of the GLUT2 promoter using nuclear extracts prepared from pancreatic islets of 12 week old db/db diabetic mice. |
| 135 | 9453241 | We show that the decreased GLUT2 mRNA expression correlates with a decrease of the GTIIa DNA-binding activity, whereas the PDX-1 binding activity is increased. |
| 136 | 9453241 | The adjunction of dexamethasone to isolated pancreatic islets, a treatment previously shown to decrease PDX-1 expression in the insulin-secreting HIT-T15 cells, has no effect on the GTIIa and PDX-1 DNA-binding activities. |
| 137 | 9460079 | Notably, three MODY genes encode transcription factors implicated in the regulation of insulin gene transcription: hepatocyte nuclear factors 1 alpha and 4 alpha, and islet duodenum homeobox-1 (IDX-1, also known as IPF-1). |
| 138 | 9460079 | Recently, mouse knockouts of the transcription factors Pax4, Pax6, beta 2/neuroD, and Isl-1 result in severe anomalies in the development of the endocrine pancreas. |
| 139 | 9472859 | Maturity-onset diabetes of the young (MODY) can be defined by the clinical characteristics of early-onset Type 2 (non-insulin-dependent) diabetes and autosomal dominant inheritance. |
| 140 | 9472859 | Mutations in four genes have been shown to cause MODY: glucokinase, hepatic nuclear factor 1 alpha (HNF1alpha), hepatic nuclear factor 4 alpha (HNF4alpha) and insulin promoter [corrected] factor 1 (IPF1). |
| 141 | 9472859 | Patients with HNF4alpha and IPF1 mutations show a similar clinical picture to HNF1alpha although diabetes may be diagnosed later. |
| 142 | 9531829 | Maturity-onset diabetes of the young (MODY) is a clinically and genetically heterogenous disorder characterized by autosomal dominant inheritance with onset usually before 25 years of age, and a primary defect in glucose-stimulated insulin secretion. |
| 143 | 9531829 | These are the genes encoding the glycolytic enzyme glucokinase, three liver-enriched transcription factors, hepatocyte nuclear factor (HNF)-1 alpha, HNF-1 beta and HNF-4 alpha, and the gene encoding the transcription factor, insulin promoter factor-1 (IPF-1). |
| 144 | 9584121 | These cells express some beta cell markers, such as islet amyloid polypeptide and Pdx1, but lack other definitive beta cell markers including glucose transporter 2 and Nkx6.1. |
| 145 | 9604866 | Reconstitution of glucotoxic HIT-T15 cells with somatostatin transcription factor-1 partially restores insulin promoter activity. |
| 146 | 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. |
| 147 | 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. |
| 148 | 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. |
| 149 | 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). |
| 150 | 9604866 | In late passage cells, transfection of STF-1 alone significantly stimulated a 2.2-fold increase in the insulin promoter activity. |
| 151 | 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. |
| 152 | 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. |
| 153 | 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. |
| 154 | 9604866 | Reconstitution of glucotoxic HIT-T15 cells with somatostatin transcription factor-1 partially restores insulin promoter activity. |
| 155 | 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. |
| 156 | 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. |
| 157 | 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. |
| 158 | 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). |
| 159 | 9604866 | In late passage cells, transfection of STF-1 alone significantly stimulated a 2.2-fold increase in the insulin promoter activity. |
| 160 | 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. |
| 161 | 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. |
| 162 | 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. |
| 163 | 9604866 | Reconstitution of glucotoxic HIT-T15 cells with somatostatin transcription factor-1 partially restores insulin promoter activity. |
| 164 | 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. |
| 165 | 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. |
| 166 | 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. |
| 167 | 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). |
| 168 | 9604866 | In late passage cells, transfection of STF-1 alone significantly stimulated a 2.2-fold increase in the insulin promoter activity. |
| 169 | 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. |
| 170 | 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. |
| 171 | 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. |
| 172 | 9604866 | Reconstitution of glucotoxic HIT-T15 cells with somatostatin transcription factor-1 partially restores insulin promoter activity. |
| 173 | 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. |
| 174 | 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. |
| 175 | 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. |
| 176 | 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). |
| 177 | 9604866 | In late passage cells, transfection of STF-1 alone significantly stimulated a 2.2-fold increase in the insulin promoter activity. |
| 178 | 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. |
| 179 | 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. |
| 180 | 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. |
| 181 | 9604866 | Reconstitution of glucotoxic HIT-T15 cells with somatostatin transcription factor-1 partially restores insulin promoter activity. |
| 182 | 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. |
| 183 | 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. |
| 184 | 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. |
| 185 | 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). |
| 186 | 9604866 | In late passage cells, transfection of STF-1 alone significantly stimulated a 2.2-fold increase in the insulin promoter activity. |
| 187 | 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. |
| 188 | 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. |
| 189 | 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. |
| 190 | 9604866 | Reconstitution of glucotoxic HIT-T15 cells with somatostatin transcription factor-1 partially restores insulin promoter activity. |
| 191 | 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. |
| 192 | 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. |
| 193 | 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. |
| 194 | 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). |
| 195 | 9604866 | In late passage cells, transfection of STF-1 alone significantly stimulated a 2.2-fold increase in the insulin promoter activity. |
| 196 | 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. |
| 197 | 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. |
| 198 | 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. |
| 199 | 9604866 | Reconstitution of glucotoxic HIT-T15 cells with somatostatin transcription factor-1 partially restores insulin promoter activity. |
| 200 | 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. |
| 201 | 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. |
| 202 | 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. |
| 203 | 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). |
| 204 | 9604866 | In late passage cells, transfection of STF-1 alone significantly stimulated a 2.2-fold increase in the insulin promoter activity. |
| 205 | 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. |
| 206 | 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. |
| 207 | 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. |
| 208 | 9604866 | Reconstitution of glucotoxic HIT-T15 cells with somatostatin transcription factor-1 partially restores insulin promoter activity. |
| 209 | 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. |
| 210 | 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. |
| 211 | 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. |
| 212 | 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). |
| 213 | 9604866 | In late passage cells, transfection of STF-1 alone significantly stimulated a 2.2-fold increase in the insulin promoter activity. |
| 214 | 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. |
| 215 | 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. |
| 216 | 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. |
| 217 | 9604866 | Reconstitution of glucotoxic HIT-T15 cells with somatostatin transcription factor-1 partially restores insulin promoter activity. |
| 218 | 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. |
| 219 | 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. |
| 220 | 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. |
| 221 | 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). |
| 222 | 9604866 | In late passage cells, transfection of STF-1 alone significantly stimulated a 2.2-fold increase in the insulin promoter activity. |
| 223 | 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. |
| 224 | 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. |
| 225 | 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. |
| 226 | 9616224 | Differential expression of the insulin gene transcriptional repressor CCAAT/enhancer-binding protein beta and transactivator islet duodenum homeobox-1 in rat pancreatic beta cells during the development of diabetes mellitus. |
| 227 | 9616224 | Impaired functions of the transactivating factors islet duodenum homeobox-1 (IDX-1) and RIPE3b-binding proteins have been implicated in the pathological downregulation of insulin gene transcription by high glucose levels in pancreatic beta cell lines in vitro, and, similarly, the exposure of pancreatic islets to fatty acids decreases IDX-1 expression. |
| 228 | 9616224 | Previously, we identified the basic leucine zipper transcription factor CCAAT/enhancer-binding protein beta (C/ EBPbeta) as an inhibitor of insulin gene transcription in pancreatic beta cells and showed that the expression of C/EBPbeta is upregulated in insulinoma-derived beta cell lines by sustained high glucose concentrations. |
| 229 | 9616224 | Here we describe the regulation of the expression of IDX-1, C/EBPbeta, and insulin at the mRNA and protein levels in pancreatic islets in animal models of diabetes mellitus. |
| 230 | 9616224 | Concomitant with a downregulation of IDX-1 and insulin expression, C/EBPbeta is upregulated in association with the manifestation of hyperglycemia during the development of diabetes in the Zucker diabetic fatty (fa/fa) rat and in the 90% pancreatectomy rat model of diabetes. |
| 231 | 9616224 | Our findings indicate that the differential dysregulation of both IDX-1 and C/EBPbeta, in response to sustained hyperglycemia or hyperlipidemia, may be involved in the impairment of insulin gene expression during the manifestation of diabetes mellitus. |
| 232 | 9616224 | Differential expression of the insulin gene transcriptional repressor CCAAT/enhancer-binding protein beta and transactivator islet duodenum homeobox-1 in rat pancreatic beta cells during the development of diabetes mellitus. |
| 233 | 9616224 | Impaired functions of the transactivating factors islet duodenum homeobox-1 (IDX-1) and RIPE3b-binding proteins have been implicated in the pathological downregulation of insulin gene transcription by high glucose levels in pancreatic beta cell lines in vitro, and, similarly, the exposure of pancreatic islets to fatty acids decreases IDX-1 expression. |
| 234 | 9616224 | Previously, we identified the basic leucine zipper transcription factor CCAAT/enhancer-binding protein beta (C/ EBPbeta) as an inhibitor of insulin gene transcription in pancreatic beta cells and showed that the expression of C/EBPbeta is upregulated in insulinoma-derived beta cell lines by sustained high glucose concentrations. |
| 235 | 9616224 | Here we describe the regulation of the expression of IDX-1, C/EBPbeta, and insulin at the mRNA and protein levels in pancreatic islets in animal models of diabetes mellitus. |
| 236 | 9616224 | Concomitant with a downregulation of IDX-1 and insulin expression, C/EBPbeta is upregulated in association with the manifestation of hyperglycemia during the development of diabetes in the Zucker diabetic fatty (fa/fa) rat and in the 90% pancreatectomy rat model of diabetes. |
| 237 | 9616224 | Our findings indicate that the differential dysregulation of both IDX-1 and C/EBPbeta, in response to sustained hyperglycemia or hyperlipidemia, may be involved in the impairment of insulin gene expression during the manifestation of diabetes mellitus. |
| 238 | 9616224 | Differential expression of the insulin gene transcriptional repressor CCAAT/enhancer-binding protein beta and transactivator islet duodenum homeobox-1 in rat pancreatic beta cells during the development of diabetes mellitus. |
| 239 | 9616224 | Impaired functions of the transactivating factors islet duodenum homeobox-1 (IDX-1) and RIPE3b-binding proteins have been implicated in the pathological downregulation of insulin gene transcription by high glucose levels in pancreatic beta cell lines in vitro, and, similarly, the exposure of pancreatic islets to fatty acids decreases IDX-1 expression. |
| 240 | 9616224 | Previously, we identified the basic leucine zipper transcription factor CCAAT/enhancer-binding protein beta (C/ EBPbeta) as an inhibitor of insulin gene transcription in pancreatic beta cells and showed that the expression of C/EBPbeta is upregulated in insulinoma-derived beta cell lines by sustained high glucose concentrations. |
| 241 | 9616224 | Here we describe the regulation of the expression of IDX-1, C/EBPbeta, and insulin at the mRNA and protein levels in pancreatic islets in animal models of diabetes mellitus. |
| 242 | 9616224 | Concomitant with a downregulation of IDX-1 and insulin expression, C/EBPbeta is upregulated in association with the manifestation of hyperglycemia during the development of diabetes in the Zucker diabetic fatty (fa/fa) rat and in the 90% pancreatectomy rat model of diabetes. |
| 243 | 9616224 | Our findings indicate that the differential dysregulation of both IDX-1 and C/EBPbeta, in response to sustained hyperglycemia or hyperlipidemia, may be involved in the impairment of insulin gene expression during the manifestation of diabetes mellitus. |
| 244 | 9616224 | Differential expression of the insulin gene transcriptional repressor CCAAT/enhancer-binding protein beta and transactivator islet duodenum homeobox-1 in rat pancreatic beta cells during the development of diabetes mellitus. |
| 245 | 9616224 | Impaired functions of the transactivating factors islet duodenum homeobox-1 (IDX-1) and RIPE3b-binding proteins have been implicated in the pathological downregulation of insulin gene transcription by high glucose levels in pancreatic beta cell lines in vitro, and, similarly, the exposure of pancreatic islets to fatty acids decreases IDX-1 expression. |
| 246 | 9616224 | Previously, we identified the basic leucine zipper transcription factor CCAAT/enhancer-binding protein beta (C/ EBPbeta) as an inhibitor of insulin gene transcription in pancreatic beta cells and showed that the expression of C/EBPbeta is upregulated in insulinoma-derived beta cell lines by sustained high glucose concentrations. |
| 247 | 9616224 | Here we describe the regulation of the expression of IDX-1, C/EBPbeta, and insulin at the mRNA and protein levels in pancreatic islets in animal models of diabetes mellitus. |
| 248 | 9616224 | Concomitant with a downregulation of IDX-1 and insulin expression, C/EBPbeta is upregulated in association with the manifestation of hyperglycemia during the development of diabetes in the Zucker diabetic fatty (fa/fa) rat and in the 90% pancreatectomy rat model of diabetes. |
| 249 | 9616224 | Our findings indicate that the differential dysregulation of both IDX-1 and C/EBPbeta, in response to sustained hyperglycemia or hyperlipidemia, may be involved in the impairment of insulin gene expression during the manifestation of diabetes mellitus. |
| 250 | 9628281 | In this study 88 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were diagnosed as diabetic at less than 40 years of age, 55 patients with insulin-dependent-diabetes (IDDM), and 67 normal control subjects were analysed for variants in the upstream region of the IPF1 gene by direct sequencing. |
| 251 | 9637677 | These mice develop diabetes with age, and we show that IPF1/PDX1 is required for maintaining the beta cell identity by positively regulating insulin and islet amyloid polypeptide expression and by repressing glucagon expression. |
| 252 | 9637677 | We also provide evidence that IPF1/PDX1 regulates the expression of Glut2 in a dosage-dependent manner suggesting that lowered IPF1/PDX1 activity may contribute to the development of type II diabetes by causing impaired expression of both Glut2 and insulin. |
| 253 | 9637677 | These mice develop diabetes with age, and we show that IPF1/PDX1 is required for maintaining the beta cell identity by positively regulating insulin and islet amyloid polypeptide expression and by repressing glucagon expression. |
| 254 | 9637677 | We also provide evidence that IPF1/PDX1 regulates the expression of Glut2 in a dosage-dependent manner suggesting that lowered IPF1/PDX1 activity may contribute to the development of type II diabetes by causing impaired expression of both Glut2 and insulin. |
| 255 | 9649577 | This circumstance suggests that the mechanism of diabetes in these individuals may be due not only to reduced gene dosage, but also to a dominant negative inhibition of transcription of the insulin gene and other beta cell-specific genes regulated by the mutant IPF-1. |
| 256 | 9736233 | Maturity-onset diabetes of the young (MODY) is a form of diabetes mellitus characterized by autosomal dominant inheritance, onset usually before 25 y of age and a primary defect in glucose-stimulated insulin secretion. |
| 257 | 9736233 | Mutations in the genes encoding the glycolytic enzyme glucokinase, the liver-enriched transcription factors, hepatocyte nuclear factor-1alpha (HNF-1alpha), HNF-1beta and HNF-4alpha, and the transcription factor, insulin promoter factor-1 (IPF-1) have all been associated with MODY. |
| 258 | 9736233 | The results presented here indicate that the glucokinase form of MODY occurs in Norway. |
| 259 | 9754819 | Maturity-onset diabetes of the young (MODY) is a heterogeneous subtype of non-insulin-dependent diabetes mellitus characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. |
| 260 | 9754819 | To date five MODY genes have been identified: hepatocyte nuclear factor-4 alpha (HNF-4alpha/MODY1/TCF14) on chromosome 20q, glucokinase (GCK/MODY2) on chromosome 7p, hepatocyte nuclear factor-1 alpha (HNF-1alpha/MODY3/TCF1) on chromosome 12q, insulin promoter factor-1 (IPF1/MODY4) on chromosome 13q and hepatocyte nuclear factor-1 beta (HNF-1beta/MODY5/TCF2) on chromosome 17cen-q. |
| 261 | 9754819 | We have screened the HNF-4alpha, HNF-1alpha and HNF-1beta genes in members of 18 MODY kindreds who tested negative for glucokinase mutations. |
| 262 | 9754819 | Five missense (G31D, R159W, A161T, R200W, R271W), one substitution at the splice donor site of intron 5 (IVS5nt + 2T-->A) and one deletion mutation (P379fsdelT) were found in the HNF-1alpha gene, but no MODY-associated mutations were found in the HNF-4alpha and HNF-1beta genes. |
| 263 | 9754819 | Of 67 French MODY families that we have now studied, 42 (63%) have mutations in the glucokinase gene, 14 (21%) have mutations in the HNF-1alpha gene, and 11 (16%) have no mutations in the HNF-4alpha, IPF1 and HNF-1beta genes. |
| 264 | 9754819 | Maturity-onset diabetes of the young (MODY) is a heterogeneous subtype of non-insulin-dependent diabetes mellitus characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. |
| 265 | 9754819 | To date five MODY genes have been identified: hepatocyte nuclear factor-4 alpha (HNF-4alpha/MODY1/TCF14) on chromosome 20q, glucokinase (GCK/MODY2) on chromosome 7p, hepatocyte nuclear factor-1 alpha (HNF-1alpha/MODY3/TCF1) on chromosome 12q, insulin promoter factor-1 (IPF1/MODY4) on chromosome 13q and hepatocyte nuclear factor-1 beta (HNF-1beta/MODY5/TCF2) on chromosome 17cen-q. |
| 266 | 9754819 | We have screened the HNF-4alpha, HNF-1alpha and HNF-1beta genes in members of 18 MODY kindreds who tested negative for glucokinase mutations. |
| 267 | 9754819 | Five missense (G31D, R159W, A161T, R200W, R271W), one substitution at the splice donor site of intron 5 (IVS5nt + 2T-->A) and one deletion mutation (P379fsdelT) were found in the HNF-1alpha gene, but no MODY-associated mutations were found in the HNF-4alpha and HNF-1beta genes. |
| 268 | 9754819 | Of 67 French MODY families that we have now studied, 42 (63%) have mutations in the glucokinase gene, 14 (21%) have mutations in the HNF-1alpha gene, and 11 (16%) have no mutations in the HNF-4alpha, IPF1 and HNF-1beta genes. |
| 269 | 9780731 | Maturity-onset diabetes of the young (MODY) is a monogenic form of non-insulin-dependent diabetes mellitus (NIDDM) characterized by an early age of onset, often in childhood or adolescence and usually < 25 years of age, and autosomal dominant inheritance. |
| 270 | 9780731 | Clinical characterization of patients with MODY indicates that impaired insulin secretion is the primary defect responsible for the hyperglycemia in these patients. |
| 271 | 9780731 | Genetic studies have thus far identified five MODY susceptibility genes, four of which encode transcription factors; HNF (hepatocyte nuclear factor)-1 alpha, HNF-1 beta, HNF-4 alpha, and IPF1. |
| 272 | 9887471 | Recent studies have shown that mutations in four transcription factors, hepatocyte nuclear factor-4 alpha (HNF-4 alpha), hepatocyte nuclear factor-1 alpha (HNF-1 alpha), hepatocyte nuclear factor-1 beta (HNF-1 beta), and insulin promoter factor-1 (IPF-1), are responsible for maturity onset diabetes of the young (MODY) which is characterised by an early age of onset and autosomal dominant inheritance. |
| 273 | 9887471 | Some mutations in HNF-1 alpha were identified in subjects with atypical forms of insulin-dependent diabetes, and a mutation in HNF-4 alpha and several mutations in IPF-1 were found in type 2 diabetic families with typical late-onset NIDDM. |
| 274 | 9920109 | Mutations in 5 different genes [the hepatocyte nuclear factor (HNF)-4alpha), glucokinase, HNF-1alpha, insulin promoter factor-1, and HNF-1beta genes] have been shown to cause maturity onset diabetes of the young (MODY). |
| 275 | 10078550 | Islet duodenal homeobox 1 (IDX-1/PF-1/STF-1/PDX-1), a homeodomain protein that transactivates the insulin promoter, has been shown by targeted gene ablation to be required for pancreatic development. |
| 276 | 10199131 | Until now five genes (HNF-4 alpha, glucokinase, HNF-1 alpha, IPF-1 and HNF-1 beta), whose mutation can result in MODY, insulin and insulin receptor genes, and mitochondria DNA have been reported to be responsible for diabetes. |
| 277 | 10322408 | Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of Type 2 diabetes characterized by early onset, autosomal dominant inheritance and primary defects in insulin secretion. |
| 278 | 10322408 | To date, five proteins have been identified whose genetic absence or impairment causes MODY, the enzyme glucokinase (GCK/MODY2) and four transcription factors: hepatocyte nuclear factor 4alpha (HNF-4alpha/MODY1), HNF-1alpha/MODY3, insulin promoter factor 1 (IPF-1/MODY4) and HNF-1beta/MODY5. |
| 279 | 10331405 | We believe that the cells resulting from these cultures are of beta-cell origin, since they uniformly express the transcription factor PDX-1 (STF-1, IDX-1, IPF-1), which is initially seen only in cells positive for insulin and negative for the ductal cell marker cytokeratin (CK)-19. |
| 280 | 10331405 | Although the expanded beta-cells continued to express PDX-1, insulin expression was lost over time. |
| 281 | 10331405 | We believe that the cells resulting from these cultures are of beta-cell origin, since they uniformly express the transcription factor PDX-1 (STF-1, IDX-1, IPF-1), which is initially seen only in cells positive for insulin and negative for the ductal cell marker cytokeratin (CK)-19. |
| 282 | 10331405 | Although the expanded beta-cells continued to express PDX-1, insulin expression was lost over time. |
| 283 | 10377278 | Transcription factors such as Pdx1, p48 and Nkx2.2 have been shown to be essential for the proper differentiation of exocrine and endocrine tissue; however, pancreas development also involves intricate interactions between the pancreatic epithelium and its surrounding mesenchyme. |
| 284 | 10417964 | To date, mutations in genes of five proteins have been shown to cause MODY: glucokinase (MODY2), hepatic nuclear factor-1 alpha (HNF-1 alpha) (MODY3), hepatic nuclear factor-4 alpha (HNF-4 alpha) (MODY1), insulin promoter factor 1 (IPF-1) (MODY4) and hepatic nuclear factor-1 beta (HNF-1 beta) (MODY5), but other MODY genes still await elucidation. |
| 285 | 10433248 | Finally, electrophoretic mobility shift assays using nuclear extracts from neural cells revealed the presence of IDX1/IPF1 bound to a putative homeodomain protein DNA-binding site present in the promoter of the glial fibrillary acidic protein gene. |
| 286 | 10440129 | Glucagon-like peptide-1 promotes DNA synthesis, activates phosphatidylinositol 3-kinase and increases transcription factor pancreatic and duodenal homeobox gene 1 (PDX-1) DNA binding activity in beta (INS-1)-cells. |
| 287 | 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. |
| 288 | 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. |
| 289 | 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. |
| 290 | 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. |
| 291 | 10499550 | Glucagon-like peptide-1 regulates the beta cell transcription factor, PDX-1, in insulinoma cells. |
| 292 | 10499550 | Glucagon-like peptide-1 (GLP-1) enhances insulin biosynthesis and secretion as well as transcription of the insulin, GLUT2 and glucokinase genes. |
| 293 | 10499550 | We investigated the possibility that GLP-1 may be having its long-term pleiotropic effects through a hitherto unknown regulation of PDX-1. |
| 294 | 10499550 | We found that PDX-1 mRNA level was significantly increased (p<0.01) after 2 hours and insulin mRNA level was subsequently increased (p<0.01) after 3 hours of treatment with GLP-1 (10 nM) in RIN 1046-38 insulinoma cells. |
| 295 | 10499550 | Overexpression of PDX-1 in these cells confirmed the finding of the wild type cells such that GLP-1 induced a 2-fold increase in whole cell extracts and a 3-fold increase in nuclear extracts of PDX-1 protein levels. |
| 296 | 10499550 | The results of electrophoretic mobility shift experiments showed that PDX-1 protein binding to the Al element of the rat insulin II promoter was also increased 2 h post treatment with GLP-1. |
| 297 | 10499550 | Glucagon-like peptide-1 regulates the beta cell transcription factor, PDX-1, in insulinoma cells. |
| 298 | 10499550 | Glucagon-like peptide-1 (GLP-1) enhances insulin biosynthesis and secretion as well as transcription of the insulin, GLUT2 and glucokinase genes. |
| 299 | 10499550 | We investigated the possibility that GLP-1 may be having its long-term pleiotropic effects through a hitherto unknown regulation of PDX-1. |
| 300 | 10499550 | We found that PDX-1 mRNA level was significantly increased (p<0.01) after 2 hours and insulin mRNA level was subsequently increased (p<0.01) after 3 hours of treatment with GLP-1 (10 nM) in RIN 1046-38 insulinoma cells. |
| 301 | 10499550 | Overexpression of PDX-1 in these cells confirmed the finding of the wild type cells such that GLP-1 induced a 2-fold increase in whole cell extracts and a 3-fold increase in nuclear extracts of PDX-1 protein levels. |
| 302 | 10499550 | The results of electrophoretic mobility shift experiments showed that PDX-1 protein binding to the Al element of the rat insulin II promoter was also increased 2 h post treatment with GLP-1. |
| 303 | 10499550 | Glucagon-like peptide-1 regulates the beta cell transcription factor, PDX-1, in insulinoma cells. |
| 304 | 10499550 | Glucagon-like peptide-1 (GLP-1) enhances insulin biosynthesis and secretion as well as transcription of the insulin, GLUT2 and glucokinase genes. |
| 305 | 10499550 | We investigated the possibility that GLP-1 may be having its long-term pleiotropic effects through a hitherto unknown regulation of PDX-1. |
| 306 | 10499550 | We found that PDX-1 mRNA level was significantly increased (p<0.01) after 2 hours and insulin mRNA level was subsequently increased (p<0.01) after 3 hours of treatment with GLP-1 (10 nM) in RIN 1046-38 insulinoma cells. |
| 307 | 10499550 | Overexpression of PDX-1 in these cells confirmed the finding of the wild type cells such that GLP-1 induced a 2-fold increase in whole cell extracts and a 3-fold increase in nuclear extracts of PDX-1 protein levels. |
| 308 | 10499550 | The results of electrophoretic mobility shift experiments showed that PDX-1 protein binding to the Al element of the rat insulin II promoter was also increased 2 h post treatment with GLP-1. |
| 309 | 10499550 | Glucagon-like peptide-1 regulates the beta cell transcription factor, PDX-1, in insulinoma cells. |
| 310 | 10499550 | Glucagon-like peptide-1 (GLP-1) enhances insulin biosynthesis and secretion as well as transcription of the insulin, GLUT2 and glucokinase genes. |
| 311 | 10499550 | We investigated the possibility that GLP-1 may be having its long-term pleiotropic effects through a hitherto unknown regulation of PDX-1. |
| 312 | 10499550 | We found that PDX-1 mRNA level was significantly increased (p<0.01) after 2 hours and insulin mRNA level was subsequently increased (p<0.01) after 3 hours of treatment with GLP-1 (10 nM) in RIN 1046-38 insulinoma cells. |
| 313 | 10499550 | Overexpression of PDX-1 in these cells confirmed the finding of the wild type cells such that GLP-1 induced a 2-fold increase in whole cell extracts and a 3-fold increase in nuclear extracts of PDX-1 protein levels. |
| 314 | 10499550 | The results of electrophoretic mobility shift experiments showed that PDX-1 protein binding to the Al element of the rat insulin II promoter was also increased 2 h post treatment with GLP-1. |
| 315 | 10499550 | Glucagon-like peptide-1 regulates the beta cell transcription factor, PDX-1, in insulinoma cells. |
| 316 | 10499550 | Glucagon-like peptide-1 (GLP-1) enhances insulin biosynthesis and secretion as well as transcription of the insulin, GLUT2 and glucokinase genes. |
| 317 | 10499550 | We investigated the possibility that GLP-1 may be having its long-term pleiotropic effects through a hitherto unknown regulation of PDX-1. |
| 318 | 10499550 | We found that PDX-1 mRNA level was significantly increased (p<0.01) after 2 hours and insulin mRNA level was subsequently increased (p<0.01) after 3 hours of treatment with GLP-1 (10 nM) in RIN 1046-38 insulinoma cells. |
| 319 | 10499550 | Overexpression of PDX-1 in these cells confirmed the finding of the wild type cells such that GLP-1 induced a 2-fold increase in whole cell extracts and a 3-fold increase in nuclear extracts of PDX-1 protein levels. |
| 320 | 10499550 | The results of electrophoretic mobility shift experiments showed that PDX-1 protein binding to the Al element of the rat insulin II promoter was also increased 2 h post treatment with GLP-1. |
| 321 | 10512364 | In vivo prevention of hyperglycemia also prevents glucotoxic effects on PDX-1 and insulin gene expression. |
| 322 | 10512364 | As glycemia increased in 12- and 16-week-old ZDF rats, we observed decrements in glucose-induced insulin secretion during static incubations of pancreatic islets and in insulin mRNA levels, PDX-1 mRNA levels, and PDX-1 protein binding to the insulin promoter compared with age-matched ZLC rats and 6-week-old ZDF rats. |
| 323 | 10512364 | Furthermore, troglitazone-treated ZDF animals had greater levels of insulin and PDX-1 mRNAs compared with untreated ZDF animals of the same ages at 12 and 16 weeks. |
| 324 | 10512364 | Our results demonstrate that chronic and progressive hyperglycemia resulting from type 2 diabetes in ZDF rats is associated with loss of insulin and PDX-1 mRNAs and loss of glucose-stimulated insulin secretion. |
| 325 | 10512364 | Prevention of hyperglycemia prevented the associated defects in insulin and PDX-1 gene expression and improved insulin secretion. |
| 326 | 10512364 | These findings provide the first in vivo evidence that prevention of progressive hyperglycemia in a model of type 2 diabetes preserves insulin and PDX-1 gene expression. |
| 327 | 10512364 | In vivo prevention of hyperglycemia also prevents glucotoxic effects on PDX-1 and insulin gene expression. |
| 328 | 10512364 | As glycemia increased in 12- and 16-week-old ZDF rats, we observed decrements in glucose-induced insulin secretion during static incubations of pancreatic islets and in insulin mRNA levels, PDX-1 mRNA levels, and PDX-1 protein binding to the insulin promoter compared with age-matched ZLC rats and 6-week-old ZDF rats. |
| 329 | 10512364 | Furthermore, troglitazone-treated ZDF animals had greater levels of insulin and PDX-1 mRNAs compared with untreated ZDF animals of the same ages at 12 and 16 weeks. |
| 330 | 10512364 | Our results demonstrate that chronic and progressive hyperglycemia resulting from type 2 diabetes in ZDF rats is associated with loss of insulin and PDX-1 mRNAs and loss of glucose-stimulated insulin secretion. |
| 331 | 10512364 | Prevention of hyperglycemia prevented the associated defects in insulin and PDX-1 gene expression and improved insulin secretion. |
| 332 | 10512364 | These findings provide the first in vivo evidence that prevention of progressive hyperglycemia in a model of type 2 diabetes preserves insulin and PDX-1 gene expression. |
| 333 | 10512364 | In vivo prevention of hyperglycemia also prevents glucotoxic effects on PDX-1 and insulin gene expression. |
| 334 | 10512364 | As glycemia increased in 12- and 16-week-old ZDF rats, we observed decrements in glucose-induced insulin secretion during static incubations of pancreatic islets and in insulin mRNA levels, PDX-1 mRNA levels, and PDX-1 protein binding to the insulin promoter compared with age-matched ZLC rats and 6-week-old ZDF rats. |
| 335 | 10512364 | Furthermore, troglitazone-treated ZDF animals had greater levels of insulin and PDX-1 mRNAs compared with untreated ZDF animals of the same ages at 12 and 16 weeks. |
| 336 | 10512364 | Our results demonstrate that chronic and progressive hyperglycemia resulting from type 2 diabetes in ZDF rats is associated with loss of insulin and PDX-1 mRNAs and loss of glucose-stimulated insulin secretion. |
| 337 | 10512364 | Prevention of hyperglycemia prevented the associated defects in insulin and PDX-1 gene expression and improved insulin secretion. |
| 338 | 10512364 | These findings provide the first in vivo evidence that prevention of progressive hyperglycemia in a model of type 2 diabetes preserves insulin and PDX-1 gene expression. |
| 339 | 10512364 | In vivo prevention of hyperglycemia also prevents glucotoxic effects on PDX-1 and insulin gene expression. |
| 340 | 10512364 | As glycemia increased in 12- and 16-week-old ZDF rats, we observed decrements in glucose-induced insulin secretion during static incubations of pancreatic islets and in insulin mRNA levels, PDX-1 mRNA levels, and PDX-1 protein binding to the insulin promoter compared with age-matched ZLC rats and 6-week-old ZDF rats. |
| 341 | 10512364 | Furthermore, troglitazone-treated ZDF animals had greater levels of insulin and PDX-1 mRNAs compared with untreated ZDF animals of the same ages at 12 and 16 weeks. |
| 342 | 10512364 | Our results demonstrate that chronic and progressive hyperglycemia resulting from type 2 diabetes in ZDF rats is associated with loss of insulin and PDX-1 mRNAs and loss of glucose-stimulated insulin secretion. |
| 343 | 10512364 | Prevention of hyperglycemia prevented the associated defects in insulin and PDX-1 gene expression and improved insulin secretion. |
| 344 | 10512364 | These findings provide the first in vivo evidence that prevention of progressive hyperglycemia in a model of type 2 diabetes preserves insulin and PDX-1 gene expression. |
| 345 | 10512364 | In vivo prevention of hyperglycemia also prevents glucotoxic effects on PDX-1 and insulin gene expression. |
| 346 | 10512364 | As glycemia increased in 12- and 16-week-old ZDF rats, we observed decrements in glucose-induced insulin secretion during static incubations of pancreatic islets and in insulin mRNA levels, PDX-1 mRNA levels, and PDX-1 protein binding to the insulin promoter compared with age-matched ZLC rats and 6-week-old ZDF rats. |
| 347 | 10512364 | Furthermore, troglitazone-treated ZDF animals had greater levels of insulin and PDX-1 mRNAs compared with untreated ZDF animals of the same ages at 12 and 16 weeks. |
| 348 | 10512364 | Our results demonstrate that chronic and progressive hyperglycemia resulting from type 2 diabetes in ZDF rats is associated with loss of insulin and PDX-1 mRNAs and loss of glucose-stimulated insulin secretion. |
| 349 | 10512364 | Prevention of hyperglycemia prevented the associated defects in insulin and PDX-1 gene expression and improved insulin secretion. |
| 350 | 10512364 | These findings provide the first in vivo evidence that prevention of progressive hyperglycemia in a model of type 2 diabetes preserves insulin and PDX-1 gene expression. |
| 351 | 10512364 | In vivo prevention of hyperglycemia also prevents glucotoxic effects on PDX-1 and insulin gene expression. |
| 352 | 10512364 | As glycemia increased in 12- and 16-week-old ZDF rats, we observed decrements in glucose-induced insulin secretion during static incubations of pancreatic islets and in insulin mRNA levels, PDX-1 mRNA levels, and PDX-1 protein binding to the insulin promoter compared with age-matched ZLC rats and 6-week-old ZDF rats. |
| 353 | 10512364 | Furthermore, troglitazone-treated ZDF animals had greater levels of insulin and PDX-1 mRNAs compared with untreated ZDF animals of the same ages at 12 and 16 weeks. |
| 354 | 10512364 | Our results demonstrate that chronic and progressive hyperglycemia resulting from type 2 diabetes in ZDF rats is associated with loss of insulin and PDX-1 mRNAs and loss of glucose-stimulated insulin secretion. |
| 355 | 10512364 | Prevention of hyperglycemia prevented the associated defects in insulin and PDX-1 gene expression and improved insulin secretion. |
| 356 | 10512364 | These findings provide the first in vivo evidence that prevention of progressive hyperglycemia in a model of type 2 diabetes preserves insulin and PDX-1 gene expression. |
| 357 | 10545531 | Functional transactivation assays of these IPF-1 mutant isoforms in a beta-pancreatic tumor cell line transfected with a transcriptional reporter and IPF-1 expression plasmids demonstrate a significant inhibition of basal insulin promoter activity (stronger with the InsCCG243 mutant). |
| 358 | 10567373 | Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a neonatal disease characterized by dysregulation of insulin secretion accompanied by profound hypoglycemia. |
| 359 | 10567373 | The PHHI-derived cell line (NES2Y) exhibits insulin secretory characteristics typical of islet cells derived from these patients, i.e. they have no K(ATP) channel activity and as a consequence secrete insulin at constitutively high levels in the absence of glucose. |
| 360 | 10567373 | In addition, they exhibit impaired expression of the homeodomain transcription factor PDX1, which is a key component of the signaling pathway linking nutrient metabolism to the regulation of insulin gene expression. |
| 361 | 10567373 | To repair these defects NES2Y cells were triple-transfected with cDNAs encoding the two components of the K(ATP) channel (SUR1 and Kir6.2) and PDX1. |
| 362 | 10567373 | This approach to engineering PHHI-derived islet cells may be of use in gene therapy for PHHI and in cell engineering techniques for administering insulin for the treatment of diabetes mellitus. |
| 363 | 10567373 | Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a neonatal disease characterized by dysregulation of insulin secretion accompanied by profound hypoglycemia. |
| 364 | 10567373 | The PHHI-derived cell line (NES2Y) exhibits insulin secretory characteristics typical of islet cells derived from these patients, i.e. they have no K(ATP) channel activity and as a consequence secrete insulin at constitutively high levels in the absence of glucose. |
| 365 | 10567373 | In addition, they exhibit impaired expression of the homeodomain transcription factor PDX1, which is a key component of the signaling pathway linking nutrient metabolism to the regulation of insulin gene expression. |
| 366 | 10567373 | To repair these defects NES2Y cells were triple-transfected with cDNAs encoding the two components of the K(ATP) channel (SUR1 and Kir6.2) and PDX1. |
| 367 | 10567373 | This approach to engineering PHHI-derived islet cells may be of use in gene therapy for PHHI and in cell engineering techniques for administering insulin for the treatment of diabetes mellitus. |
| 368 | 10567702 | Pancreatic duodenal homeobox-containing transcription factor 1 (PDX-1) plays a crucial role in pancreas development and beta-cell gene regulation. |
| 369 | 10567702 | PDX-1 has been suggested to be involved in the glucose-dependent regulation of insulin gene transcription. |
| 370 | 10567702 | Pancreatic duodenal homeobox-containing transcription factor 1 (PDX-1) plays a crucial role in pancreas development and beta-cell gene regulation. |
| 371 | 10567702 | PDX-1 has been suggested to be involved in the glucose-dependent regulation of insulin gene transcription. |
| 372 | 10580420 | To investigate if this sensitivity represents an acquired trait during beta-cell maturation, we used two in vitro cultured cell systems: 1) a pluripotent glucagon-positive pre-beta-cell phenotype (NHI-glu) that, after in vivo passage, matures into an insulin-producing beta-cell phenotype (NHI-ins) and 2) a glucagonoma cell-type (AN-glu) that, after stable transfection with pancreatic duodenal homeobox factor-1 (PDX-1), acquires the ability to produce insulin (AN-ins). |
| 373 | 10609119 | These genes encode hepatocyte nuclear factor-4 alpha (HNF-4 alpha, MODY1), glucokinase (MODY2), hepatocyte nuclear factor-1 alpha (HNF-1 alpha, MODY3), insulin promoter factor-1 (IPF-1, MODY4), and hepatocyte nuclear factor-1 beta (HNF-1 beta, MODY5). |
| 374 | 10677506 | Recent genetic studies have identified a network of transcription factors, including Pdx1, Isl1, Pax4, Pax6, NeuroD, Nkx2.2, and Hlxb9, regulating the development of islet cells at different stages, but the molecular mechanisms controlling the specification of pancreatic endocrine precursors remain unknown. neurogenin3 (ngn3) is a member of a family of basic helix-loop-helix transcription factors that is involved in the determination of neural precursor cells in the neuroectoderm. ngn3 is expressed in discrete regions of the nervous system and in scattered cells in the embryonic pancreas. |
| 375 | 10677506 | Expression of Isl1, Pax4, Pax6, and NeuroD is lost, and endocrine precursors are lacking in the mutant pancreatic epithelium. |
| 376 | 10720084 | Maturity-onset diabetes of the young (MODY) now exists in five subtypes (MODY1-5), four of which are caused by mutations in transcription factors hepatocyte nuclear factor-4alpha (HNF-4alpha), HNF-1alpha, insulin promoter factor-1 (IPF-1), and HNF-1beta (MODY1, -3, -4, and -5). |
| 377 | 10720084 | Thus, highlighting the potential role of this transcription factor in the genetic basis of Danish and Italian MODY as well as in Danish patients with late-onset type 2 diabetes mellitus, we have examined the human IPF-1 gene for mutations by single strand conformation polymorphism and heteroduplex analysis in 200 Danish patients with late-onset type 2 diabetes and in 44 Danish and Italian MODY patients. |
| 378 | 10720084 | We conclude that variants in IPF-1 are not a common cause of MODY or late-onset type 2 diabetes in the Caucasian population, and that in terms of insulin transcription both the N76 and the T140 mutations are likely to represent functionally normal IPF-1 variants with no direct role in the pathogenesis of MODY or late-onset type 2 diabetes mellitus. |
| 379 | 10720084 | Maturity-onset diabetes of the young (MODY) now exists in five subtypes (MODY1-5), four of which are caused by mutations in transcription factors hepatocyte nuclear factor-4alpha (HNF-4alpha), HNF-1alpha, insulin promoter factor-1 (IPF-1), and HNF-1beta (MODY1, -3, -4, and -5). |
| 380 | 10720084 | Thus, highlighting the potential role of this transcription factor in the genetic basis of Danish and Italian MODY as well as in Danish patients with late-onset type 2 diabetes mellitus, we have examined the human IPF-1 gene for mutations by single strand conformation polymorphism and heteroduplex analysis in 200 Danish patients with late-onset type 2 diabetes and in 44 Danish and Italian MODY patients. |
| 381 | 10720084 | We conclude that variants in IPF-1 are not a common cause of MODY or late-onset type 2 diabetes in the Caucasian population, and that in terms of insulin transcription both the N76 and the T140 mutations are likely to represent functionally normal IPF-1 variants with no direct role in the pathogenesis of MODY or late-onset type 2 diabetes mellitus. |
| 382 | 10720084 | Maturity-onset diabetes of the young (MODY) now exists in five subtypes (MODY1-5), four of which are caused by mutations in transcription factors hepatocyte nuclear factor-4alpha (HNF-4alpha), HNF-1alpha, insulin promoter factor-1 (IPF-1), and HNF-1beta (MODY1, -3, -4, and -5). |
| 383 | 10720084 | Thus, highlighting the potential role of this transcription factor in the genetic basis of Danish and Italian MODY as well as in Danish patients with late-onset type 2 diabetes mellitus, we have examined the human IPF-1 gene for mutations by single strand conformation polymorphism and heteroduplex analysis in 200 Danish patients with late-onset type 2 diabetes and in 44 Danish and Italian MODY patients. |
| 384 | 10720084 | We conclude that variants in IPF-1 are not a common cause of MODY or late-onset type 2 diabetes in the Caucasian population, and that in terms of insulin transcription both the N76 and the T140 mutations are likely to represent functionally normal IPF-1 variants with no direct role in the pathogenesis of MODY or late-onset type 2 diabetes mellitus. |
| 385 | 10851133 | We used an islet-specific regulatory element (pdx1(PB)) from pancreatic/duodenal homeobox (pdx1) gene to maintain HNF6 expression in endocrine cells beyond 18.5 d.p.c. |
| 386 | 10851133 | As glucose uptake/metabolism is essential for insulin secretion, decreased GLUT2 may contribute to the etiology of diabetes in pdx1(PB)-HNF6 transgenics. |
| 387 | 10851133 | We used an islet-specific regulatory element (pdx1(PB)) from pancreatic/duodenal homeobox (pdx1) gene to maintain HNF6 expression in endocrine cells beyond 18.5 d.p.c. |
| 388 | 10851133 | As glucose uptake/metabolism is essential for insulin secretion, decreased GLUT2 may contribute to the etiology of diabetes in pdx1(PB)-HNF6 transgenics. |
| 389 | 10866047 | Sulfonylurea receptor 1 and Kir6.2 expression in the novel human insulin-secreting cell line NES2Y. |
| 390 | 10866047 | NES2Y cells, like beta-cells isolated from the patient of origin, lack functional ATP-sensitive potassium channels (KATP) and also carry a defect in the insulin gene-regulatory transcription factor PDX1. |
| 391 | 10866047 | Here, we report that the NES2Y beta-cells that are transfected with the genes encoding the components of KATP channels in beta-cells, sulfonylurea receptor (SUR) 1 and Kir6.2, have operational KATP channels and show normal intracellular Ca2+ and secretory responses to glucose. |
| 392 | 10866047 | NES2Y beta-cells that are transfected with either Kir6.2 or SUR1 alone do not express functional KATP channels and have impaired intracellular free Ca2+ concentration-signaling responses to depolarization-dependent beta-cell agonists. |
| 393 | 10868931 | Alternatively, beta-cells have been suggested to arise late, directly from the GLUT2- and pancreatic duodenal homeobox factor-1 (PDX1)-expressing epithelium, which gives rise also to the acinar cells during this stage. |
| 394 | 10868931 | In this study, we have identified a subset of the PDX1+ epithelial cells that are marked by expression of Neurogenin3 (Ngn3). |
| 395 | 10868931 | Detailed analysis of Ngn3/paired box factor 6 (PAX6) and NeuroD/PAX6 co-expression shows that the two bHLH factors are expressed in a largely nonoverlapping set of cells, but such analysis also suggests that the NeuroD+ cells arise from cells expressing Ngn3 transiently. |
| 396 | 10868931 | NeuroD+ cells do not express Ki-67, a marker of proliferating cells, which shows that these cells are postmitotic. |
| 397 | 10868931 | The earliest sign of alpha-cell development appears to be Brain4 expression, which apparently precedes Islet-1 (ISL1) expression. |
| 398 | 10868931 | Alternatively, beta-cells have been suggested to arise late, directly from the GLUT2- and pancreatic duodenal homeobox factor-1 (PDX1)-expressing epithelium, which gives rise also to the acinar cells during this stage. |
| 399 | 10868931 | In this study, we have identified a subset of the PDX1+ epithelial cells that are marked by expression of Neurogenin3 (Ngn3). |
| 400 | 10868931 | Detailed analysis of Ngn3/paired box factor 6 (PAX6) and NeuroD/PAX6 co-expression shows that the two bHLH factors are expressed in a largely nonoverlapping set of cells, but such analysis also suggests that the NeuroD+ cells arise from cells expressing Ngn3 transiently. |
| 401 | 10868931 | NeuroD+ cells do not express Ki-67, a marker of proliferating cells, which shows that these cells are postmitotic. |
| 402 | 10868931 | The earliest sign of alpha-cell development appears to be Brain4 expression, which apparently precedes Islet-1 (ISL1) expression. |
| 403 | 10868948 | Mutations in the transcription factors hepatocyte nuclear factor (HNF)-4alpha and -1alpha, insulin promoter factor-1, and HNF-1beta are the causes of four forms of maturity-onset diabetes of the young (MODY1 and 3-5, respectively). |
| 404 | 10868948 | The winged-helix transcription factor HNF-3beta has been implicated in the regulation of expression of each of these MODY genes, suggesting that mutations in the HNF-3beta gene (HNF3B) may also cause MODY. |
| 405 | 10868949 | Because the HNF-3beta gene is implicated in this network, we screened it for mutations in 21 probands of French ancestry with clinical diagnosis of MODY and early-onset type 2 diabetes. |
| 406 | 10868949 | All of the five known MODY genes, HNF-4alpha, glucokinase, HNF-1alpha, HNF-1beta, and IPF1, were previously excluded as being the cause of diabetes in these families. |
| 407 | 10868954 | After a 24-h culture with IL-1beta (30 U/ml), beta-cells exhibited a lower expression of the beta-cell-specific protein transcription factor pancreatic and duodenal homeobox gene (PDX)-1, glucose transporter GLUT2, and proinsulin convertase PC2, with a marked reduction (60-70%) in glucose-induced insulin production and selective sensitivity to the toxins alloxan (ALX) and streptozotocin (STZ). |
| 408 | 10868954 | On the other hand, the cells presented an increased expression of Mn-superoxide dismutase, heat shock protein 70, inducible heme oxygenase, and inducible nitrite oxide synthase. |
| 409 | 10868954 | Exposure to IL-1beta can thus protect beta-cells against conditions that cause necrosis; however, it did not protect against apoptosis induced by the additional presence of interferon-gamma or tumor necrosis factor-alpha. |
| 410 | 10868963 | Glucose modulation of insulin mRNA levels is dependent on transcription factor PDX-1 and occurs independently of changes in intracellular Ca2+. |
| 411 | 10868963 | These effects are partially mediated through the activity of a homeodomain transcription factor, PDX-1, which binds to four sites within the human insulin gene promoter. |
| 412 | 10868963 | The availability of a human beta-like cell line, NES2Y, which lacks PDX-1 but expresses the insulin gene, allowed us to determine whether PDX-1 was essential for the stimulatory effect of glucose on insulin mRNA levels. |
| 413 | 10868963 | However, in NES2Y cells stably transfected with PDX-1 (NES-PDX-1), glucose exhibited a marked stimulatory effect on both the insulin promoter (5+/-0.2-fold, n = 6) and insulin mRNA levels (4.8+/-0.5-fold, n = 4). |
| 414 | 10868963 | Despite the loss of control of Ca2+ channel activity, NES-PDX-1 cells maintained normal glucose-responsive insulin gene regulation. |
| 415 | 10868963 | These results demonstrate that glucose modulation of insulin mRNA levels is dependent on the activity of PDX-1 and that these effects are independent of changes in intracellular Ca2+ concentrations. |
| 416 | 10868963 | Glucose modulation of insulin mRNA levels is dependent on transcription factor PDX-1 and occurs independently of changes in intracellular Ca2+. |
| 417 | 10868963 | These effects are partially mediated through the activity of a homeodomain transcription factor, PDX-1, which binds to four sites within the human insulin gene promoter. |
| 418 | 10868963 | The availability of a human beta-like cell line, NES2Y, which lacks PDX-1 but expresses the insulin gene, allowed us to determine whether PDX-1 was essential for the stimulatory effect of glucose on insulin mRNA levels. |
| 419 | 10868963 | However, in NES2Y cells stably transfected with PDX-1 (NES-PDX-1), glucose exhibited a marked stimulatory effect on both the insulin promoter (5+/-0.2-fold, n = 6) and insulin mRNA levels (4.8+/-0.5-fold, n = 4). |
| 420 | 10868963 | Despite the loss of control of Ca2+ channel activity, NES-PDX-1 cells maintained normal glucose-responsive insulin gene regulation. |
| 421 | 10868963 | These results demonstrate that glucose modulation of insulin mRNA levels is dependent on the activity of PDX-1 and that these effects are independent of changes in intracellular Ca2+ concentrations. |
| 422 | 10868963 | Glucose modulation of insulin mRNA levels is dependent on transcription factor PDX-1 and occurs independently of changes in intracellular Ca2+. |
| 423 | 10868963 | These effects are partially mediated through the activity of a homeodomain transcription factor, PDX-1, which binds to four sites within the human insulin gene promoter. |
| 424 | 10868963 | The availability of a human beta-like cell line, NES2Y, which lacks PDX-1 but expresses the insulin gene, allowed us to determine whether PDX-1 was essential for the stimulatory effect of glucose on insulin mRNA levels. |
| 425 | 10868963 | However, in NES2Y cells stably transfected with PDX-1 (NES-PDX-1), glucose exhibited a marked stimulatory effect on both the insulin promoter (5+/-0.2-fold, n = 6) and insulin mRNA levels (4.8+/-0.5-fold, n = 4). |
| 426 | 10868963 | Despite the loss of control of Ca2+ channel activity, NES-PDX-1 cells maintained normal glucose-responsive insulin gene regulation. |
| 427 | 10868963 | These results demonstrate that glucose modulation of insulin mRNA levels is dependent on the activity of PDX-1 and that these effects are independent of changes in intracellular Ca2+ concentrations. |
| 428 | 10868963 | Glucose modulation of insulin mRNA levels is dependent on transcription factor PDX-1 and occurs independently of changes in intracellular Ca2+. |
| 429 | 10868963 | These effects are partially mediated through the activity of a homeodomain transcription factor, PDX-1, which binds to four sites within the human insulin gene promoter. |
| 430 | 10868963 | The availability of a human beta-like cell line, NES2Y, which lacks PDX-1 but expresses the insulin gene, allowed us to determine whether PDX-1 was essential for the stimulatory effect of glucose on insulin mRNA levels. |
| 431 | 10868963 | However, in NES2Y cells stably transfected with PDX-1 (NES-PDX-1), glucose exhibited a marked stimulatory effect on both the insulin promoter (5+/-0.2-fold, n = 6) and insulin mRNA levels (4.8+/-0.5-fold, n = 4). |
| 432 | 10868963 | Despite the loss of control of Ca2+ channel activity, NES-PDX-1 cells maintained normal glucose-responsive insulin gene regulation. |
| 433 | 10868963 | These results demonstrate that glucose modulation of insulin mRNA levels is dependent on the activity of PDX-1 and that these effects are independent of changes in intracellular Ca2+ concentrations. |
| 434 | 10868963 | Glucose modulation of insulin mRNA levels is dependent on transcription factor PDX-1 and occurs independently of changes in intracellular Ca2+. |
| 435 | 10868963 | These effects are partially mediated through the activity of a homeodomain transcription factor, PDX-1, which binds to four sites within the human insulin gene promoter. |
| 436 | 10868963 | The availability of a human beta-like cell line, NES2Y, which lacks PDX-1 but expresses the insulin gene, allowed us to determine whether PDX-1 was essential for the stimulatory effect of glucose on insulin mRNA levels. |
| 437 | 10868963 | However, in NES2Y cells stably transfected with PDX-1 (NES-PDX-1), glucose exhibited a marked stimulatory effect on both the insulin promoter (5+/-0.2-fold, n = 6) and insulin mRNA levels (4.8+/-0.5-fold, n = 4). |
| 438 | 10868963 | Despite the loss of control of Ca2+ channel activity, NES-PDX-1 cells maintained normal glucose-responsive insulin gene regulation. |
| 439 | 10868963 | These results demonstrate that glucose modulation of insulin mRNA levels is dependent on the activity of PDX-1 and that these effects are independent of changes in intracellular Ca2+ concentrations. |
| 440 | 10868963 | Glucose modulation of insulin mRNA levels is dependent on transcription factor PDX-1 and occurs independently of changes in intracellular Ca2+. |
| 441 | 10868963 | These effects are partially mediated through the activity of a homeodomain transcription factor, PDX-1, which binds to four sites within the human insulin gene promoter. |
| 442 | 10868963 | The availability of a human beta-like cell line, NES2Y, which lacks PDX-1 but expresses the insulin gene, allowed us to determine whether PDX-1 was essential for the stimulatory effect of glucose on insulin mRNA levels. |
| 443 | 10868963 | However, in NES2Y cells stably transfected with PDX-1 (NES-PDX-1), glucose exhibited a marked stimulatory effect on both the insulin promoter (5+/-0.2-fold, n = 6) and insulin mRNA levels (4.8+/-0.5-fold, n = 4). |
| 444 | 10868963 | Despite the loss of control of Ca2+ channel activity, NES-PDX-1 cells maintained normal glucose-responsive insulin gene regulation. |
| 445 | 10868963 | These results demonstrate that glucose modulation of insulin mRNA levels is dependent on the activity of PDX-1 and that these effects are independent of changes in intracellular Ca2+ concentrations. |
| 446 | 10871194 | After isolation and culture, both duct and islet cell preparations contained the Ipf-1 immunoreactive proteins p42 and p45 (42 and 45 kDa, respectively) in similar proportions, but the expression levels were twofold lower in duct cells. |
| 447 | 10871194 | After 4 h of labeling, the endocrine cells exhibited a sevenfold higher phosphorylation of p42 than the duct cells, whereas p45 was phosphorylated only in endocrine cells. |
| 448 | 10899756 | Gene expression studies have shown that HNF3 proteins are critical regulators of the early-onset type 2 diabetes genes HNF-1 alpha, HNF-4 alpha and IPF-1/PDX-1 (MODY3, 1 and 4, respectively) and of glucagon transcription and pancreatic alpha-cell function. |
| 449 | 10905482 | Insulinotropic glucagon-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas. |
| 450 | 10905482 | Here, we show that the insulinotropic hormone glucagon-like peptide (GLP)-1, which is produced by the intestine, enhances the pancreatic expression of the homeodomain transcription factor IDX-1 that is critical for pancreas development and the transcriptional regulation of the insulin gene. |
| 451 | 10905482 | Concomitantly, GLP-1 administered to diabetic mice stimulates insulin secretion and effectively lowers their blood sugar levels. |
| 452 | 10905482 | Thus, in addition to stimulating insulin secretion, GLP-1 stimulates the expression of the transcription factor IDX-1 while stimulating beta-cell neogenesis and may thereby be an effective treatment for diabetes. |
| 453 | 10905482 | Insulinotropic glucagon-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas. |
| 454 | 10905482 | Here, we show that the insulinotropic hormone glucagon-like peptide (GLP)-1, which is produced by the intestine, enhances the pancreatic expression of the homeodomain transcription factor IDX-1 that is critical for pancreas development and the transcriptional regulation of the insulin gene. |
| 455 | 10905482 | Concomitantly, GLP-1 administered to diabetic mice stimulates insulin secretion and effectively lowers their blood sugar levels. |
| 456 | 10905482 | Thus, in addition to stimulating insulin secretion, GLP-1 stimulates the expression of the transcription factor IDX-1 while stimulating beta-cell neogenesis and may thereby be an effective treatment for diabetes. |
| 457 | 10905482 | Insulinotropic glucagon-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas. |
| 458 | 10905482 | Here, we show that the insulinotropic hormone glucagon-like peptide (GLP)-1, which is produced by the intestine, enhances the pancreatic expression of the homeodomain transcription factor IDX-1 that is critical for pancreas development and the transcriptional regulation of the insulin gene. |
| 459 | 10905482 | Concomitantly, GLP-1 administered to diabetic mice stimulates insulin secretion and effectively lowers their blood sugar levels. |
| 460 | 10905482 | Thus, in addition to stimulating insulin secretion, GLP-1 stimulates the expression of the transcription factor IDX-1 while stimulating beta-cell neogenesis and may thereby be an effective treatment for diabetes. |
| 461 | 10909415 | We demonstrated that PDX-1 is sufficient to activate the endogenous, otherwise silent, mouse insulin 1 and 2 and pro-insulin convertase gene expression in liver. |
| 462 | 10909415 | PDX-1 expression in liver resulted in a 25-fold increase in hepatic immunoreactive insulin content and a threefold increase in plasma immunoreactive insulin levels, as compared to control adenovirus-treated mice. |
| 463 | 10909415 | Hepatic immunoreactive insulin, induced by PDX-1, was processed to mature mI-1 and mI-2 and was biologically active; it ameliorated hyperglycemia in streptozotocin-treated diabetic mice. |
| 464 | 10909415 | We demonstrated that PDX-1 is sufficient to activate the endogenous, otherwise silent, mouse insulin 1 and 2 and pro-insulin convertase gene expression in liver. |
| 465 | 10909415 | PDX-1 expression in liver resulted in a 25-fold increase in hepatic immunoreactive insulin content and a threefold increase in plasma immunoreactive insulin levels, as compared to control adenovirus-treated mice. |
| 466 | 10909415 | Hepatic immunoreactive insulin, induced by PDX-1, was processed to mature mI-1 and mI-2 and was biologically active; it ameliorated hyperglycemia in streptozotocin-treated diabetic mice. |
| 467 | 10909415 | We demonstrated that PDX-1 is sufficient to activate the endogenous, otherwise silent, mouse insulin 1 and 2 and pro-insulin convertase gene expression in liver. |
| 468 | 10909415 | PDX-1 expression in liver resulted in a 25-fold increase in hepatic immunoreactive insulin content and a threefold increase in plasma immunoreactive insulin levels, as compared to control adenovirus-treated mice. |
| 469 | 10909415 | Hepatic immunoreactive insulin, induced by PDX-1, was processed to mature mI-1 and mI-2 and was biologically active; it ameliorated hyperglycemia in streptozotocin-treated diabetic mice. |
| 470 | 10943822 | Mutations in hepatocyte nuclear factor-4alpha, hepatocyte nuclear factor-1alpha, insulin promoter factor-1 and hepatocyte nuclear factor-1beta, respectively, cause MODY1, MODY3, MODY4, and MODY5. |
| 471 | 10953613 | Mutations in the glucokinase gene and the genes for the transcription factors HNF-1 alpha, HNF-4 alpha, IPF-1, HNF-1 beta y HNF-3 beta have been demonstrated to cause MODY, a subtype of NIDDM characterized by autosomal dominate pattern of inheritance and an early-onset. |
| 472 | 10953613 | Mutations in any of the genes associated to MODY may contribute to the insulin secretion deficiency frequently observed in early-onset type 2 diabetic patients. |
| 473 | 10967107 | During pancreatic development, the paired homeodomain transcription factor PAX4 is required for the differentiation of the insulin-producing beta cells and somatostatin-producing delta cells. |
| 474 | 10967107 | Serial deletions through this region reveal the presence of positive elements that bind several pancreatic transcription factors as follows: the POU homeodomain factor HNF1alpha, the orphan nuclear receptor HNF4alpha, the homeodomain factor PDX1, and a heterodimer composed of two basic helix-loop-helix factors. |
| 475 | 10969830 | The c-Jun amino-terminal kinase pathway is preferentially activated by interleukin-1 and controls apoptosis in differentiating pancreatic beta-cells. |
| 476 | 10969830 | To characterize the differentiation events that selectively target insulin-producing cells to interleukin (IL)-1beta-induced apoptosis, we studied IL-1beta signaling via mitogen-activated protein kinase (MAPK) and stress-activated protein kinase in 2 pancreatic endocrine cell lines. |
| 477 | 10969830 | We studied the glucagon-secreting AN-glu cell line and the insulin and the islet amyloid polypeptide-producing beta-cell line (AN-ins cells), which is derived by stable transfection of AN-glu cells with the transcription factor pancreatic duodenal homeobox factor-1. |
| 478 | 10969830 | This increased sensitivity was not associated with a more pronounced IL-l-induced nitric oxide production in AN-ins cells, but it correlated with a more marked activation of the 3 MAPKs extracellular signal-regulated kinases (ERKs)-1/2, c-Jun NH2-terminal kinase (JNK), and p38 MAPK (p38). |
| 479 | 10969830 | This led to increased phosphorylation of the transcription factors c-Jun, Elk-1, and ATF2 and of heat shock protein 25. |
| 480 | 10969830 | Inhibition of ERK-1/2 and p38 did not prevent but aggravated IL-1beta-induced cell death. |
| 481 | 10969830 | Cell death could be elicited by overexpressing the catalytic domain of MAPK kinase kinase 1, a specific activator of JNK and nuclear factor-kappaB, which does not recruit ERK-1/2 or p38. |
| 482 | 10969830 | Coactivation of ERK-1/2 with JNK did not prevent apoptosis. |
| 483 | 10969830 | In conclusion, increased MAPK signaling in response to IL-1beta may represent a novel molecular marker of beta-cell differentiation. |
| 484 | 11016451 | Adult human cytokeratin 19-positive cells reexpress insulin promoter factor 1 in vitro: further evidence for pluripotent pancreatic stem cells in humans. |
| 485 | 11016451 | We investigated the protein and mRNA expression of insulin promoter factor 1 (IPF-1) (or pancreas/duodenal homeobox 1), a transcription factor critical for pancreatic development and endocrine cell neogenesis, in human pancreatic ductal cells derived from cultured exocrine tissue. |
| 486 | 11016451 | Double immunocytochemistry showed direct evidence that IPF-1 appeared during culture in these exocrine-derived ductal cells (cytokeratin 7-positive) and was not merely in contaminating endocrine cells (chromogranin A-positive). |
| 487 | 11016451 | Adult human cytokeratin 19-positive cells reexpress insulin promoter factor 1 in vitro: further evidence for pluripotent pancreatic stem cells in humans. |
| 488 | 11016451 | We investigated the protein and mRNA expression of insulin promoter factor 1 (IPF-1) (or pancreas/duodenal homeobox 1), a transcription factor critical for pancreatic development and endocrine cell neogenesis, in human pancreatic ductal cells derived from cultured exocrine tissue. |
| 489 | 11016451 | Double immunocytochemistry showed direct evidence that IPF-1 appeared during culture in these exocrine-derived ductal cells (cytokeratin 7-positive) and was not merely in contaminating endocrine cells (chromogranin A-positive). |
| 490 | 11016451 | Adult human cytokeratin 19-positive cells reexpress insulin promoter factor 1 in vitro: further evidence for pluripotent pancreatic stem cells in humans. |
| 491 | 11016451 | We investigated the protein and mRNA expression of insulin promoter factor 1 (IPF-1) (or pancreas/duodenal homeobox 1), a transcription factor critical for pancreatic development and endocrine cell neogenesis, in human pancreatic ductal cells derived from cultured exocrine tissue. |
| 492 | 11016451 | Double immunocytochemistry showed direct evidence that IPF-1 appeared during culture in these exocrine-derived ductal cells (cytokeratin 7-positive) and was not merely in contaminating endocrine cells (chromogranin A-positive). |
| 493 | 11024035 | Transcription factors (PDX-1 and HNF-1 alpha) binding to A elements are critical regulators of insulin gene expression and/or pancreatic development. |
| 494 | 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. |
| 495 | 11058894 | MODY is genetically heterogeneous with five different genes identified to date: hepatocyte nuclear factor-4 alpha (HNF-4 alpha) [MODY1]; glucokinase [MODY2]; hepatocyte nuclear factor-1 alpha (HNF-1 alpha) [MODY3]; insulin promoter factor-1 (IPF-1) [MODY4]; and hepatocyte nuclear factor-1 beta (HNF-1 beta) [MODY5]. |
| 496 | 11058894 | Mutations in the HNF-1 alpha gene represent a common cause of MODY in the majority of populations studied. |
| 497 | 11058894 | The identification of an HNF-1 alpha gene mutation in a patient with type 2 diabetes confirms the diagnosis of MODY and has important implications for clinical management. |
| 498 | 11075995 | IFN-gamma overexpression within the pancreas is not sufficient to rescue Pax4, Pax6, and Pdx-1 mutant mice from death. |
| 499 | 11075995 | We analyzed the effect of a transgene on lethality in mice lacking the transcription factors Pax4, Pax6, or Pdx-1, by intercrossing such mice with transgenic mice whose pancreatic cells make IFN-gamma (ins-IFN-gamma mice). |
| 500 | 11075995 | This outcome demonstrates that the pathway for IFN-gamma regeneration requires the participation of Pax4, Pax6, and Pdx-1. |
| 501 | 11075995 | IFN-gamma overexpression within the pancreas is not sufficient to rescue Pax4, Pax6, and Pdx-1 mutant mice from death. |
| 502 | 11075995 | We analyzed the effect of a transgene on lethality in mice lacking the transcription factors Pax4, Pax6, or Pdx-1, by intercrossing such mice with transgenic mice whose pancreatic cells make IFN-gamma (ins-IFN-gamma mice). |
| 503 | 11075995 | This outcome demonstrates that the pathway for IFN-gamma regeneration requires the participation of Pax4, Pax6, and Pdx-1. |
| 504 | 11075995 | IFN-gamma overexpression within the pancreas is not sufficient to rescue Pax4, Pax6, and Pdx-1 mutant mice from death. |
| 505 | 11075995 | We analyzed the effect of a transgene on lethality in mice lacking the transcription factors Pax4, Pax6, or Pdx-1, by intercrossing such mice with transgenic mice whose pancreatic cells make IFN-gamma (ins-IFN-gamma mice). |
| 506 | 11075995 | This outcome demonstrates that the pathway for IFN-gamma regeneration requires the participation of Pax4, Pax6, and Pdx-1. |
| 507 | 11090239 | Cell proliferation nuclear antigen (PCNA) was used as a marker of cell proliferation and cells were stained for putative markers of islet neogenesis, cytokeratin 20 (CK20) and Bcl-2. |
| 508 | 11090239 | Most of the insulin(+)clusters were also homeodomain-containing transcription factor pancreas duodenum homeobox gene-1 (PDX-1) positive. |
| 509 | 11108273 | Glucagon-like peptide-1 induces cell proliferation and pancreatic-duodenum homeobox-1 expression and increases endocrine cell mass in the pancreas of old, glucose-intolerant rats. |
| 510 | 11108273 | Here, we show that continuous infusion of glucagon-like peptide-1 (7-36) (GLP-1; an insulinotropic agent), to young and old animals, had effects on the beta-cell of the pancreas other than simply on the insulin secretory apparatus. |
| 511 | 11108273 | Our current results in both young and old rats demonstrate that treatment caused an up-regulation of pancreatic-duodenum homeobox-1 (PDX-1) expression in islets and total pancreas, induced pancreatic cell proliferation, and beta-cell neogenesis. |
| 512 | 11108273 | The effects on levels of PDX-1 messenger RNA were abrogated by simultaneous infusion of Exendin (9-39), a specific antagonist of GLP-1. |
| 513 | 11108273 | Glucagon-like peptide-1 induces cell proliferation and pancreatic-duodenum homeobox-1 expression and increases endocrine cell mass in the pancreas of old, glucose-intolerant rats. |
| 514 | 11108273 | Here, we show that continuous infusion of glucagon-like peptide-1 (7-36) (GLP-1; an insulinotropic agent), to young and old animals, had effects on the beta-cell of the pancreas other than simply on the insulin secretory apparatus. |
| 515 | 11108273 | Our current results in both young and old rats demonstrate that treatment caused an up-regulation of pancreatic-duodenum homeobox-1 (PDX-1) expression in islets and total pancreas, induced pancreatic cell proliferation, and beta-cell neogenesis. |
| 516 | 11108273 | The effects on levels of PDX-1 messenger RNA were abrogated by simultaneous infusion of Exendin (9-39), a specific antagonist of GLP-1. |
| 517 | 11118882 | This promoter region contains sequence motifs that have been shown to be involved in beta-cell-specific expression of insulin, Pdx1 and islet amyloid polypeptide (IAPP). |
| 518 | 11130726 | Here we show that the FGF receptors (FGFRs) 1 and 2, together with the ligands FGF1, FGF2, FGF4, FGF5, FGF7 and FGF10, are expressed in adult mouse beta-cells, indicating that FGF signalling may have a role in differentiated beta-cells. |
| 519 | 11130726 | We also show that Ipf1/Pdx1 is required for the expression of FGFR1 signalling components in beta-cells, indicating that Ipf1/Pdx1 acts upstream of FGFR1 signalling in beta-cells to maintain proper glucose sensing, insulin processing and glucose homeostasis. |
| 520 | 11181516 | An antiserum directed against the transcription factor islet duodenum homeobox-1 (IDX-1), a regulator of pancreas development and activator of the insulin gene promoter, attenuated the binding activity of Hh-responsive protein complexes. |
| 521 | 11181516 | Nuclear IDX-1 protein levels on Western blots were increased by ectopic Hh expression, thereby providing a mechanism for Hh-mediated regulation of the insulin promoter. |
| 522 | 11181516 | Thus, the IDX-1 gene is a direct regulatory target of Hh signaling in insulin-producing pancreatic beta-cells. |
| 523 | 11181516 | We propose that Hh signaling activates the insulin gene promoter indirectly via the direct activation of IDX-1 expression. |
| 524 | 11181516 | Because IDX-1 gene expression is essential for insulin gene expression, pancreatic beta-cell development, and normal glucose homeostasis, our findings that Hh signaling regulates IDX-1 expression in the endocrine pancreas suggest possible novel therapeutic approaches for diabetes mellitus. |
| 525 | 11181516 | An antiserum directed against the transcription factor islet duodenum homeobox-1 (IDX-1), a regulator of pancreas development and activator of the insulin gene promoter, attenuated the binding activity of Hh-responsive protein complexes. |
| 526 | 11181516 | Nuclear IDX-1 protein levels on Western blots were increased by ectopic Hh expression, thereby providing a mechanism for Hh-mediated regulation of the insulin promoter. |
| 527 | 11181516 | Thus, the IDX-1 gene is a direct regulatory target of Hh signaling in insulin-producing pancreatic beta-cells. |
| 528 | 11181516 | We propose that Hh signaling activates the insulin gene promoter indirectly via the direct activation of IDX-1 expression. |
| 529 | 11181516 | Because IDX-1 gene expression is essential for insulin gene expression, pancreatic beta-cell development, and normal glucose homeostasis, our findings that Hh signaling regulates IDX-1 expression in the endocrine pancreas suggest possible novel therapeutic approaches for diabetes mellitus. |
| 530 | 11181516 | An antiserum directed against the transcription factor islet duodenum homeobox-1 (IDX-1), a regulator of pancreas development and activator of the insulin gene promoter, attenuated the binding activity of Hh-responsive protein complexes. |
| 531 | 11181516 | Nuclear IDX-1 protein levels on Western blots were increased by ectopic Hh expression, thereby providing a mechanism for Hh-mediated regulation of the insulin promoter. |
| 532 | 11181516 | Thus, the IDX-1 gene is a direct regulatory target of Hh signaling in insulin-producing pancreatic beta-cells. |
| 533 | 11181516 | We propose that Hh signaling activates the insulin gene promoter indirectly via the direct activation of IDX-1 expression. |
| 534 | 11181516 | Because IDX-1 gene expression is essential for insulin gene expression, pancreatic beta-cell development, and normal glucose homeostasis, our findings that Hh signaling regulates IDX-1 expression in the endocrine pancreas suggest possible novel therapeutic approaches for diabetes mellitus. |
| 535 | 11181516 | An antiserum directed against the transcription factor islet duodenum homeobox-1 (IDX-1), a regulator of pancreas development and activator of the insulin gene promoter, attenuated the binding activity of Hh-responsive protein complexes. |
| 536 | 11181516 | Nuclear IDX-1 protein levels on Western blots were increased by ectopic Hh expression, thereby providing a mechanism for Hh-mediated regulation of the insulin promoter. |
| 537 | 11181516 | Thus, the IDX-1 gene is a direct regulatory target of Hh signaling in insulin-producing pancreatic beta-cells. |
| 538 | 11181516 | We propose that Hh signaling activates the insulin gene promoter indirectly via the direct activation of IDX-1 expression. |
| 539 | 11181516 | Because IDX-1 gene expression is essential for insulin gene expression, pancreatic beta-cell development, and normal glucose homeostasis, our findings that Hh signaling regulates IDX-1 expression in the endocrine pancreas suggest possible novel therapeutic approaches for diabetes mellitus. |
| 540 | 11181516 | An antiserum directed against the transcription factor islet duodenum homeobox-1 (IDX-1), a regulator of pancreas development and activator of the insulin gene promoter, attenuated the binding activity of Hh-responsive protein complexes. |
| 541 | 11181516 | Nuclear IDX-1 protein levels on Western blots were increased by ectopic Hh expression, thereby providing a mechanism for Hh-mediated regulation of the insulin promoter. |
| 542 | 11181516 | Thus, the IDX-1 gene is a direct regulatory target of Hh signaling in insulin-producing pancreatic beta-cells. |
| 543 | 11181516 | We propose that Hh signaling activates the insulin gene promoter indirectly via the direct activation of IDX-1 expression. |
| 544 | 11181516 | Because IDX-1 gene expression is essential for insulin gene expression, pancreatic beta-cell development, and normal glucose homeostasis, our findings that Hh signaling regulates IDX-1 expression in the endocrine pancreas suggest possible novel therapeutic approaches for diabetes mellitus. |
| 545 | 11202217 | The subgroups that result in non-insulin-dependent DM in children are as follows: the 'honeymoon' phase of type 1 DM, type 2 DM, genetic syndromes accompanied by DM, and maturity-onset diabetes of the young (MODY). |
| 546 | 11202217 | It should be emphasized that MODY comprises two discrete clinical syndromes: glucokinase diabetes and transcription factor diabetes, the latter of which results from mutations in the genes encoding hepatocyte nuclear factor (HNF)-1alpha, HNF-1beta, HNF-4alpha and insulin promoter factor-1. |
| 547 | 11222748 | Induction of beta-cell differentiation was achieved by stimulating the signaling pathways downstream of the transcription factor PDX-1, cell-cell contact, and the glucagon-like peptide (GLP-1) receptor. |
| 548 | 11237222 | Glucagon-like peptide-1 (GLP-1) is a potent insulin secretagogue that has multiple synergetic effects on the glucose-dependent insulin secretion pathways of the beta-cell. |
| 549 | 11237222 | Our investigations into the mechanisms of action of GLP-1 began by using the reverse hemolytic plaque assay to quantify insulin secretion from individual cells of the RIN 1046-38 insulinoma cell line in response to acute treatment with the peptide. |
| 550 | 11237222 | GLP-1 increases both the number of cells secreting insulin and the amount secreted per cell. |
| 551 | 11237222 | This response to GLP-1 is retained even in the beta cell of the old (i.e., 22-month), glucose-intolerant Wistar rat, which exhibits a normal, first-phase insulin response to glucose following an acute bolus of GLP-1. |
| 552 | 11237222 | Preincubation with GLP-1 (24 hours) potentiates glucose- and GLP-1-dependent insulin secretion and increases insulin content in the insulinoma cells. |
| 553 | 11237222 | Treatment of old Wistar rats for 48 hours with GLP-1 leads to normalization of the insulin response and an increase in islet insulin content and mRNA levels of GLUT 2 and glucokinase. |
| 554 | 11237222 | PDX-1, a transcriptional factor activator of these three genes, also is upregulated in the insulinoma cell line in aged rats and diabetic mice following treatment with GLP-1. |
| 555 | 11237222 | Administration of GLP-1 to old rats leads to pancreatic cell proliferation, insulin-positive clusters, and an increase in beta-cell mass. |
| 556 | 11237222 | Thus, the actions of GLP-1 on the beta-cell are complex, with possible benefits to the diabetic patient that extend beyond a simple glucose-dependent increase in insulin secretion. |
| 557 | 11246869 | Characterization of the mouse islet-specific glucose-6-phosphatase catalytic subunit-related protein gene promoter by in situ footprinting: correlation with fusion gene expression in the islet-derived betaTC-3 and hamster insulinoma tumor cell lines. |
| 558 | 11246869 | To begin to investigate the molecular basis for the islet-specific expression of the IGRP gene, a series of truncated IGRP-chloramphenicol acetyltransferase (CAT) fusion genes were transiently transfected into the islet-derived mouse betaTC-3 and hamster insulinoma tumor cell lines. |
| 559 | 11246869 | The data suggest that hepatocyte nuclear factor 3 may be important for basal IGRP gene expression, as it is for glucagon, GLUT2, and Pdx-1 gene expression. |
| 560 | 11246871 | Nestin-positive cells within pancreatic islets express neither the hormones insulin, glucagon, somatostatin, or pancreatic polypeptide nor the markers of vascular endothelium or neurons, such as collagen IV and galanin. |
| 561 | 11246871 | Nestin-positive cells in the islets and in pancreatic ducts are distinct from ductal epithelium because they do not express the ductal marker cytokeratin 19 (CK19). |
| 562 | 11246871 | Upon confluence, they are able to differentiate into cells that express liver and exocrine pancreas markers, such as alpha-fetoprotein and pancreatic amylase, and display a ductal/endocrine phenotype with expression of CK19, neural-specific cell adhesion molecule, insulin, glucagon, and the pancreas/duodenum specific homeodomain transcription factor, IDX-1. |
| 563 | 11246894 | Mutations in transcription factors that play a role in the development of the endocrine pancreas, such as insulin promoter factor-1 and NeuroD1/BETA2, have been associated with diabetes. |
| 564 | 11249068 | PDX-1 plays a critical role in pancreatic development and insulin secretion. |
| 565 | 11249068 | The ARIP and ARIP/PDX-1 cells were treated with known growth and differentiation factors including hepatocyte growth factor, activin A, betacellulin, reg, INGAP, nicotinamide, and retinoic acid. |
| 566 | 11249068 | PDX-1 plays a critical role in pancreatic development and insulin secretion. |
| 567 | 11249068 | The ARIP and ARIP/PDX-1 cells were treated with known growth and differentiation factors including hepatocyte growth factor, activin A, betacellulin, reg, INGAP, nicotinamide, and retinoic acid. |
| 568 | 11272167 | The resulting depletion of the insulin stores may be related to deficient glucose-regulated insulin gene transcription, possibly due to defective PDX-1 (pancreatic duodenal homeobox factor-1) expression in the adult P. obesus. |
| 569 | 11272171 | beta-cell-specific expression of insulin and PDX-1 genes. |
| 570 | 11272175 | Defective glucose-regulated insulin gene expression associated with PDX-1 deficiency in the Psammomys obesus model of type 2 diabetes. |
| 571 | 11272177 | The lack of IR did not result in major changes in the expression of islet hormone genes or of beta-cell-specific marker genes encoding pancreas duodenum homeobox-containing transcription factor-1 (PDX-1), glucokinase (GCK), and GLUT2, as shown by reverse transcriptase-polymerase chain reaction analysis. |
| 572 | 11272196 | PDX-1 was shown to be expressed early during development in cells of both exocrine and endocrine origin; later it becomes restricted primarily to beta-cells where it regulates the expression of beta-cell-specific genes and mediates the glucose effect on insulin gene transcription. |
| 573 | 11272196 | This comparison revealed three short conserved regions, designated PH1, PH2, and PH3. |
| 574 | 11272196 | We showed that HNF-3beta can bind and stimulate the activity of the human PH1 and PH2 elements in non-beta-cells. |
| 575 | 11272196 | Results reported by Wu et al. (7) and Sharma et al. (6) also indicate that expression of the mouse pdx-1 is controlled by an HNF-3-like element. |
| 576 | 11272196 | Thus, it can be stated that at least some aspects of pdx-1 expression rely on the transcription factor HNF-3beta. |
| 577 | 11272196 | Because HNF-3beta is not restricted to beta-cells, the selective transcription of pdx-1 is likely to rely on additional factors. |
| 578 | 11272196 | Our findings that the PH1 enhancer element binds both HNF-3beta and PDX-1 and that mutations in each individual site dramatically impair its transcriptional activity suggest that these factors cooperate with one another. |
| 579 | 11272196 | PDX-1 was shown to be expressed early during development in cells of both exocrine and endocrine origin; later it becomes restricted primarily to beta-cells where it regulates the expression of beta-cell-specific genes and mediates the glucose effect on insulin gene transcription. |
| 580 | 11272196 | This comparison revealed three short conserved regions, designated PH1, PH2, and PH3. |
| 581 | 11272196 | We showed that HNF-3beta can bind and stimulate the activity of the human PH1 and PH2 elements in non-beta-cells. |
| 582 | 11272196 | Results reported by Wu et al. (7) and Sharma et al. (6) also indicate that expression of the mouse pdx-1 is controlled by an HNF-3-like element. |
| 583 | 11272196 | Thus, it can be stated that at least some aspects of pdx-1 expression rely on the transcription factor HNF-3beta. |
| 584 | 11272196 | Because HNF-3beta is not restricted to beta-cells, the selective transcription of pdx-1 is likely to rely on additional factors. |
| 585 | 11272196 | Our findings that the PH1 enhancer element binds both HNF-3beta and PDX-1 and that mutations in each individual site dramatically impair its transcriptional activity suggest that these factors cooperate with one another. |
| 586 | 11272196 | PDX-1 was shown to be expressed early during development in cells of both exocrine and endocrine origin; later it becomes restricted primarily to beta-cells where it regulates the expression of beta-cell-specific genes and mediates the glucose effect on insulin gene transcription. |
| 587 | 11272196 | This comparison revealed three short conserved regions, designated PH1, PH2, and PH3. |
| 588 | 11272196 | We showed that HNF-3beta can bind and stimulate the activity of the human PH1 and PH2 elements in non-beta-cells. |
| 589 | 11272196 | Results reported by Wu et al. (7) and Sharma et al. (6) also indicate that expression of the mouse pdx-1 is controlled by an HNF-3-like element. |
| 590 | 11272196 | Thus, it can be stated that at least some aspects of pdx-1 expression rely on the transcription factor HNF-3beta. |
| 591 | 11272196 | Because HNF-3beta is not restricted to beta-cells, the selective transcription of pdx-1 is likely to rely on additional factors. |
| 592 | 11272196 | Our findings that the PH1 enhancer element binds both HNF-3beta and PDX-1 and that mutations in each individual site dramatically impair its transcriptional activity suggest that these factors cooperate with one another. |
| 593 | 11272196 | PDX-1 was shown to be expressed early during development in cells of both exocrine and endocrine origin; later it becomes restricted primarily to beta-cells where it regulates the expression of beta-cell-specific genes and mediates the glucose effect on insulin gene transcription. |
| 594 | 11272196 | This comparison revealed three short conserved regions, designated PH1, PH2, and PH3. |
| 595 | 11272196 | We showed that HNF-3beta can bind and stimulate the activity of the human PH1 and PH2 elements in non-beta-cells. |
| 596 | 11272196 | Results reported by Wu et al. (7) and Sharma et al. (6) also indicate that expression of the mouse pdx-1 is controlled by an HNF-3-like element. |
| 597 | 11272196 | Thus, it can be stated that at least some aspects of pdx-1 expression rely on the transcription factor HNF-3beta. |
| 598 | 11272196 | Because HNF-3beta is not restricted to beta-cells, the selective transcription of pdx-1 is likely to rely on additional factors. |
| 599 | 11272196 | Our findings that the PH1 enhancer element binds both HNF-3beta and PDX-1 and that mutations in each individual site dramatically impair its transcriptional activity suggest that these factors cooperate with one another. |
| 600 | 11272196 | PDX-1 was shown to be expressed early during development in cells of both exocrine and endocrine origin; later it becomes restricted primarily to beta-cells where it regulates the expression of beta-cell-specific genes and mediates the glucose effect on insulin gene transcription. |
| 601 | 11272196 | This comparison revealed three short conserved regions, designated PH1, PH2, and PH3. |
| 602 | 11272196 | We showed that HNF-3beta can bind and stimulate the activity of the human PH1 and PH2 elements in non-beta-cells. |
| 603 | 11272196 | Results reported by Wu et al. (7) and Sharma et al. (6) also indicate that expression of the mouse pdx-1 is controlled by an HNF-3-like element. |
| 604 | 11272196 | Thus, it can be stated that at least some aspects of pdx-1 expression rely on the transcription factor HNF-3beta. |
| 605 | 11272196 | Because HNF-3beta is not restricted to beta-cells, the selective transcription of pdx-1 is likely to rely on additional factors. |
| 606 | 11272196 | Our findings that the PH1 enhancer element binds both HNF-3beta and PDX-1 and that mutations in each individual site dramatically impair its transcriptional activity suggest that these factors cooperate with one another. |
| 607 | 11272211 | beta-Cell transcription factor genes are important in the pathophysiology of the beta-cell, with mutations in hepatocyte nuclear factor (HNF)-1alpha, HNF-4alpha, insulin promoter factor (IPF)-1, HNF-1beta, and NeuroD1/BETA2, all resulting in early-onset type 2 diabetes. |
| 608 | 11272211 | The relative distribution of the 90 families fitting maturity-onset diabetes of the young (MODY) criteria was 63% HNF-1alpha, 2% HNF-4alpha, 0% IPF-1, 1% HNF-1beta, 0% NeuroD1/ BETA2, and 20% glucokinase. |
| 609 | 11272211 | IPF-1 mutations are associated with a higher age at diagnosis (42.7 years) than HNF-1alpha (20.4 years), HNF-1beta (24.2 years), or HNF-4alpha (26.3 years) gene mutations. |
| 610 | 11289043 | Glucagon-like peptide 1 induces differentiation of islet duodenal homeobox-1-positive pancreatic ductal cells into insulin-secreting cells. |
| 611 | 11289043 | Whether the antidiabetic properties of GLP-1 are exclusively due to its insulin secretory activity remains to be determined. |
| 612 | 11289043 | The aim of this study was to investigate whether pancreatic ductal epithelial cells could be differentiated into insulin-secreting cells by exposing them to GLP-1. |
| 613 | 11289043 | A major difference distinguishes these two cell lines: whereas ARIP cells spontaneously express the beta-cell differentiation factor islet duodenal homeobox-1 (IDX-1), PANC-1 cells are characteristically IDX-1 negative. |
| 614 | 11289043 | GLP-1 induced the differentiation of ARIP cells into insulin-synthesizing cells, although it did not affect the phenotype of PANC-1 cells, as determined by fluorescence-activated cell sorting (FACS) analysis. |
| 615 | 11289043 | Differentiation of ARIP cells by exposure to human GLP-1 occurs in a time- and dose-dependent manner, and this is associated with an increase in IDX-1 and insulin mRNA levels. |
| 616 | 11289043 | Interestingly, PANC-1 cells, when stably transfected with human IDX-1, gained responsiveness to GLP-1 and were able to differentiate into beta-cells, as determined by FACS analysis, insulin gene expression, intracellular insulin content, and insulin accumulation in the culture medium. |
| 617 | 11289043 | Finally, we demonstrated that the receptor for GLP-1 is constitutively expressed by ARIP and PANC-1 cells and that the mRNA level for this transcript was increased by cellular transfection with human IDX-1. |
| 618 | 11289043 | In summary, our study provides evidence that GLP-1 is a differentiation factor for pancreatic ductal cells and that its effect requires the expression of IDX-1. |
| 619 | 11289043 | Glucagon-like peptide 1 induces differentiation of islet duodenal homeobox-1-positive pancreatic ductal cells into insulin-secreting cells. |
| 620 | 11289043 | Whether the antidiabetic properties of GLP-1 are exclusively due to its insulin secretory activity remains to be determined. |
| 621 | 11289043 | The aim of this study was to investigate whether pancreatic ductal epithelial cells could be differentiated into insulin-secreting cells by exposing them to GLP-1. |
| 622 | 11289043 | A major difference distinguishes these two cell lines: whereas ARIP cells spontaneously express the beta-cell differentiation factor islet duodenal homeobox-1 (IDX-1), PANC-1 cells are characteristically IDX-1 negative. |
| 623 | 11289043 | GLP-1 induced the differentiation of ARIP cells into insulin-synthesizing cells, although it did not affect the phenotype of PANC-1 cells, as determined by fluorescence-activated cell sorting (FACS) analysis. |
| 624 | 11289043 | Differentiation of ARIP cells by exposure to human GLP-1 occurs in a time- and dose-dependent manner, and this is associated with an increase in IDX-1 and insulin mRNA levels. |
| 625 | 11289043 | Interestingly, PANC-1 cells, when stably transfected with human IDX-1, gained responsiveness to GLP-1 and were able to differentiate into beta-cells, as determined by FACS analysis, insulin gene expression, intracellular insulin content, and insulin accumulation in the culture medium. |
| 626 | 11289043 | Finally, we demonstrated that the receptor for GLP-1 is constitutively expressed by ARIP and PANC-1 cells and that the mRNA level for this transcript was increased by cellular transfection with human IDX-1. |
| 627 | 11289043 | In summary, our study provides evidence that GLP-1 is a differentiation factor for pancreatic ductal cells and that its effect requires the expression of IDX-1. |
| 628 | 11289043 | Glucagon-like peptide 1 induces differentiation of islet duodenal homeobox-1-positive pancreatic ductal cells into insulin-secreting cells. |
| 629 | 11289043 | Whether the antidiabetic properties of GLP-1 are exclusively due to its insulin secretory activity remains to be determined. |
| 630 | 11289043 | The aim of this study was to investigate whether pancreatic ductal epithelial cells could be differentiated into insulin-secreting cells by exposing them to GLP-1. |
| 631 | 11289043 | A major difference distinguishes these two cell lines: whereas ARIP cells spontaneously express the beta-cell differentiation factor islet duodenal homeobox-1 (IDX-1), PANC-1 cells are characteristically IDX-1 negative. |
| 632 | 11289043 | GLP-1 induced the differentiation of ARIP cells into insulin-synthesizing cells, although it did not affect the phenotype of PANC-1 cells, as determined by fluorescence-activated cell sorting (FACS) analysis. |
| 633 | 11289043 | Differentiation of ARIP cells by exposure to human GLP-1 occurs in a time- and dose-dependent manner, and this is associated with an increase in IDX-1 and insulin mRNA levels. |
| 634 | 11289043 | Interestingly, PANC-1 cells, when stably transfected with human IDX-1, gained responsiveness to GLP-1 and were able to differentiate into beta-cells, as determined by FACS analysis, insulin gene expression, intracellular insulin content, and insulin accumulation in the culture medium. |
| 635 | 11289043 | Finally, we demonstrated that the receptor for GLP-1 is constitutively expressed by ARIP and PANC-1 cells and that the mRNA level for this transcript was increased by cellular transfection with human IDX-1. |
| 636 | 11289043 | In summary, our study provides evidence that GLP-1 is a differentiation factor for pancreatic ductal cells and that its effect requires the expression of IDX-1. |
| 637 | 11289043 | Glucagon-like peptide 1 induces differentiation of islet duodenal homeobox-1-positive pancreatic ductal cells into insulin-secreting cells. |
| 638 | 11289043 | Whether the antidiabetic properties of GLP-1 are exclusively due to its insulin secretory activity remains to be determined. |
| 639 | 11289043 | The aim of this study was to investigate whether pancreatic ductal epithelial cells could be differentiated into insulin-secreting cells by exposing them to GLP-1. |
| 640 | 11289043 | A major difference distinguishes these two cell lines: whereas ARIP cells spontaneously express the beta-cell differentiation factor islet duodenal homeobox-1 (IDX-1), PANC-1 cells are characteristically IDX-1 negative. |
| 641 | 11289043 | GLP-1 induced the differentiation of ARIP cells into insulin-synthesizing cells, although it did not affect the phenotype of PANC-1 cells, as determined by fluorescence-activated cell sorting (FACS) analysis. |
| 642 | 11289043 | Differentiation of ARIP cells by exposure to human GLP-1 occurs in a time- and dose-dependent manner, and this is associated with an increase in IDX-1 and insulin mRNA levels. |
| 643 | 11289043 | Interestingly, PANC-1 cells, when stably transfected with human IDX-1, gained responsiveness to GLP-1 and were able to differentiate into beta-cells, as determined by FACS analysis, insulin gene expression, intracellular insulin content, and insulin accumulation in the culture medium. |
| 644 | 11289043 | Finally, we demonstrated that the receptor for GLP-1 is constitutively expressed by ARIP and PANC-1 cells and that the mRNA level for this transcript was increased by cellular transfection with human IDX-1. |
| 645 | 11289043 | In summary, our study provides evidence that GLP-1 is a differentiation factor for pancreatic ductal cells and that its effect requires the expression of IDX-1. |
| 646 | 11289043 | Glucagon-like peptide 1 induces differentiation of islet duodenal homeobox-1-positive pancreatic ductal cells into insulin-secreting cells. |
| 647 | 11289043 | Whether the antidiabetic properties of GLP-1 are exclusively due to its insulin secretory activity remains to be determined. |
| 648 | 11289043 | The aim of this study was to investigate whether pancreatic ductal epithelial cells could be differentiated into insulin-secreting cells by exposing them to GLP-1. |
| 649 | 11289043 | A major difference distinguishes these two cell lines: whereas ARIP cells spontaneously express the beta-cell differentiation factor islet duodenal homeobox-1 (IDX-1), PANC-1 cells are characteristically IDX-1 negative. |
| 650 | 11289043 | GLP-1 induced the differentiation of ARIP cells into insulin-synthesizing cells, although it did not affect the phenotype of PANC-1 cells, as determined by fluorescence-activated cell sorting (FACS) analysis. |
| 651 | 11289043 | Differentiation of ARIP cells by exposure to human GLP-1 occurs in a time- and dose-dependent manner, and this is associated with an increase in IDX-1 and insulin mRNA levels. |
| 652 | 11289043 | Interestingly, PANC-1 cells, when stably transfected with human IDX-1, gained responsiveness to GLP-1 and were able to differentiate into beta-cells, as determined by FACS analysis, insulin gene expression, intracellular insulin content, and insulin accumulation in the culture medium. |
| 653 | 11289043 | Finally, we demonstrated that the receptor for GLP-1 is constitutively expressed by ARIP and PANC-1 cells and that the mRNA level for this transcript was increased by cellular transfection with human IDX-1. |
| 654 | 11289043 | In summary, our study provides evidence that GLP-1 is a differentiation factor for pancreatic ductal cells and that its effect requires the expression of IDX-1. |
| 655 | 11307309 | This form of diabetes can result from mutations in at least seven different genes: hepatocyte nuclear factor(HNF)-4 alpha/MODY1, glucokinase/MODY2, HNF-1 alpha/MODY3, insulin promoter factor(IPF-1)/MODY4, HNF-1 beta/MODY5, NeuroD1/MODY6 and Islet(Isl)-1/MODY7. |
| 656 | 11307309 | Mutations in HNF-1 alpha/MODY3 are the most common cause of MODY in Japanese identified to date accounting for about 15% of cases of MODY. |
| 657 | 11307309 | Mutations in the HNF-4 alpha/MODY1, glucokinase/MODY2, HNF-1 beta/MODY5 and Isl-1/MODY7 genes have also been found in Japanese; however, they are rare causes of MODY. |
| 658 | 11307309 | Patients who have mutations in the HNF-1 beta/MODY5 gene have non-diabetic kidney dysfunction including renal cysts. |
| 659 | 11307309 | Genetic approach for type 2 diabetes had done by using non-parameteric linkage analysis such as sibpair analysis which worked well and NIDDM1 and NIDDM2 have been identified to date. |
| 660 | 11307309 | The responsible gene for NIDDM1 was recently identified to be Calpain 10, and SNP43 in this gene could explain all of the evidence for linkage in Mexican American type 2 diabetes. |
| 661 | 11316746 | Glucagon-like peptide-1 causes pancreatic duodenal homeobox-1 protein translocation from the cytoplasm to the nucleus of pancreatic beta-cells by a cyclic adenosine monophosphate/protein kinase A-dependent mechanism. |
| 662 | 11316746 | Glucagon-like peptide-1 (GLP-1) enhances insulin secretion and synthesis. |
| 663 | 11316746 | It also regulates the insulin, glucokinase, and GLUT2 genes. |
| 664 | 11316746 | It mediates increases in glucose-stimulated insulin secretion by activating adenylyl cyclase and elevating free cytosolic calcium levels in the beta-cell. |
| 665 | 11316746 | In addition, GLP-1 has been shown, both in vitro and in vivo, to be involved in regulation of the transcription factor, pancreatic duodenal homeobox-1 protein (PDX-1), by increasing its total protein levels, its translocation to the nucleus and its binding and resultant increase in activity of the insulin gene promoter in beta-cells of the pancreas. |
| 666 | 11316746 | Three separate inhibitors of PKA, and a cAMP antagonist, inhibited the effects of GLP-1 on PDX-1. |
| 667 | 11316746 | Furthermore, forskolin, (which stimulates adenylyl cyclase and insulin secretion), and 8-Bromo-cAMP, (an analog of cAMP which also stimulates insulin secretion), mimicked the effects of GLP-1 on PDX-1. |
| 668 | 11316746 | Our results suggest that regulation of PDX-1 by GLP-1 occurs through activation of adenylyl cyclase and the resultant increase in intracellular cAMP, in turn, activates PKA, which ultimately leads to increases in PDX-1 protein levels and translocation of the protein to the nuclei of beta-cells. |
| 669 | 11316746 | Glucagon-like peptide-1 causes pancreatic duodenal homeobox-1 protein translocation from the cytoplasm to the nucleus of pancreatic beta-cells by a cyclic adenosine monophosphate/protein kinase A-dependent mechanism. |
| 670 | 11316746 | Glucagon-like peptide-1 (GLP-1) enhances insulin secretion and synthesis. |
| 671 | 11316746 | It also regulates the insulin, glucokinase, and GLUT2 genes. |
| 672 | 11316746 | It mediates increases in glucose-stimulated insulin secretion by activating adenylyl cyclase and elevating free cytosolic calcium levels in the beta-cell. |
| 673 | 11316746 | In addition, GLP-1 has been shown, both in vitro and in vivo, to be involved in regulation of the transcription factor, pancreatic duodenal homeobox-1 protein (PDX-1), by increasing its total protein levels, its translocation to the nucleus and its binding and resultant increase in activity of the insulin gene promoter in beta-cells of the pancreas. |
| 674 | 11316746 | Three separate inhibitors of PKA, and a cAMP antagonist, inhibited the effects of GLP-1 on PDX-1. |
| 675 | 11316746 | Furthermore, forskolin, (which stimulates adenylyl cyclase and insulin secretion), and 8-Bromo-cAMP, (an analog of cAMP which also stimulates insulin secretion), mimicked the effects of GLP-1 on PDX-1. |
| 676 | 11316746 | Our results suggest that regulation of PDX-1 by GLP-1 occurs through activation of adenylyl cyclase and the resultant increase in intracellular cAMP, in turn, activates PKA, which ultimately leads to increases in PDX-1 protein levels and translocation of the protein to the nuclei of beta-cells. |
| 677 | 11316746 | Glucagon-like peptide-1 causes pancreatic duodenal homeobox-1 protein translocation from the cytoplasm to the nucleus of pancreatic beta-cells by a cyclic adenosine monophosphate/protein kinase A-dependent mechanism. |
| 678 | 11316746 | Glucagon-like peptide-1 (GLP-1) enhances insulin secretion and synthesis. |
| 679 | 11316746 | It also regulates the insulin, glucokinase, and GLUT2 genes. |
| 680 | 11316746 | It mediates increases in glucose-stimulated insulin secretion by activating adenylyl cyclase and elevating free cytosolic calcium levels in the beta-cell. |
| 681 | 11316746 | In addition, GLP-1 has been shown, both in vitro and in vivo, to be involved in regulation of the transcription factor, pancreatic duodenal homeobox-1 protein (PDX-1), by increasing its total protein levels, its translocation to the nucleus and its binding and resultant increase in activity of the insulin gene promoter in beta-cells of the pancreas. |
| 682 | 11316746 | Three separate inhibitors of PKA, and a cAMP antagonist, inhibited the effects of GLP-1 on PDX-1. |
| 683 | 11316746 | Furthermore, forskolin, (which stimulates adenylyl cyclase and insulin secretion), and 8-Bromo-cAMP, (an analog of cAMP which also stimulates insulin secretion), mimicked the effects of GLP-1 on PDX-1. |
| 684 | 11316746 | Our results suggest that regulation of PDX-1 by GLP-1 occurs through activation of adenylyl cyclase and the resultant increase in intracellular cAMP, in turn, activates PKA, which ultimately leads to increases in PDX-1 protein levels and translocation of the protein to the nuclei of beta-cells. |
| 685 | 11316746 | Glucagon-like peptide-1 causes pancreatic duodenal homeobox-1 protein translocation from the cytoplasm to the nucleus of pancreatic beta-cells by a cyclic adenosine monophosphate/protein kinase A-dependent mechanism. |
| 686 | 11316746 | Glucagon-like peptide-1 (GLP-1) enhances insulin secretion and synthesis. |
| 687 | 11316746 | It also regulates the insulin, glucokinase, and GLUT2 genes. |
| 688 | 11316746 | It mediates increases in glucose-stimulated insulin secretion by activating adenylyl cyclase and elevating free cytosolic calcium levels in the beta-cell. |
| 689 | 11316746 | In addition, GLP-1 has been shown, both in vitro and in vivo, to be involved in regulation of the transcription factor, pancreatic duodenal homeobox-1 protein (PDX-1), by increasing its total protein levels, its translocation to the nucleus and its binding and resultant increase in activity of the insulin gene promoter in beta-cells of the pancreas. |
| 690 | 11316746 | Three separate inhibitors of PKA, and a cAMP antagonist, inhibited the effects of GLP-1 on PDX-1. |
| 691 | 11316746 | Furthermore, forskolin, (which stimulates adenylyl cyclase and insulin secretion), and 8-Bromo-cAMP, (an analog of cAMP which also stimulates insulin secretion), mimicked the effects of GLP-1 on PDX-1. |
| 692 | 11316746 | Our results suggest that regulation of PDX-1 by GLP-1 occurs through activation of adenylyl cyclase and the resultant increase in intracellular cAMP, in turn, activates PKA, which ultimately leads to increases in PDX-1 protein levels and translocation of the protein to the nuclei of beta-cells. |
| 693 | 11423476 | The homeodomain protein PDX-1 is critical for pancreas development and is a key regulator of insulin gene expression. |
| 694 | 11423476 | Transgenic (TG) mice were generated in which PDX-1 was expressed in the exocrine pancreas using the exocrine-specific elastase-1 promoter. |
| 695 | 11423476 | The homeodomain protein PDX-1 is critical for pancreas development and is a key regulator of insulin gene expression. |
| 696 | 11423476 | Transgenic (TG) mice were generated in which PDX-1 was expressed in the exocrine pancreas using the exocrine-specific elastase-1 promoter. |
| 697 | 11457885 | Mutations in the homeodomain transcription factor IDX-1, a critical regulator of pancreas development and insulin gene transcription, confer a strong predisposition to the development of diabetes mellitus in humans. |
| 698 | 11457885 | Doxycycline-induced impairment of IDX-1 expression reduced activation of the Insulin promoter but activated the Idx-1 promoter, suggesting that pancreatic beta cells regulate IDX-1 transcription to maintain IDX-1 levels within a narrow range. |
| 699 | 11457885 | In transgenic mice that express both rtTA and the antisense ribozyme construct, impaired IDX-1 expression elevated glycated hemoglobin levels, diminished glucose tolerance, and decreased insulin/glucose ratios. |
| 700 | 11457885 | Mutations in the homeodomain transcription factor IDX-1, a critical regulator of pancreas development and insulin gene transcription, confer a strong predisposition to the development of diabetes mellitus in humans. |
| 701 | 11457885 | Doxycycline-induced impairment of IDX-1 expression reduced activation of the Insulin promoter but activated the Idx-1 promoter, suggesting that pancreatic beta cells regulate IDX-1 transcription to maintain IDX-1 levels within a narrow range. |
| 702 | 11457885 | In transgenic mice that express both rtTA and the antisense ribozyme construct, impaired IDX-1 expression elevated glycated hemoglobin levels, diminished glucose tolerance, and decreased insulin/glucose ratios. |
| 703 | 11457885 | Mutations in the homeodomain transcription factor IDX-1, a critical regulator of pancreas development and insulin gene transcription, confer a strong predisposition to the development of diabetes mellitus in humans. |
| 704 | 11457885 | Doxycycline-induced impairment of IDX-1 expression reduced activation of the Insulin promoter but activated the Idx-1 promoter, suggesting that pancreatic beta cells regulate IDX-1 transcription to maintain IDX-1 levels within a narrow range. |
| 705 | 11457885 | In transgenic mice that express both rtTA and the antisense ribozyme construct, impaired IDX-1 expression elevated glycated hemoglobin levels, diminished glucose tolerance, and decreased insulin/glucose ratios. |
| 706 | 11467342 | Unusual causes of diabetes have been identified, including autosomal dominant, single gene forms due to mutations of glucokinase, the hepatocyte nuclear factors, and insulin promoter factor 1. |
| 707 | 11473041 | The homeodomain transcription factor IPF1/PDX1 is required in beta-cells for efficient expression of insulin, glucose transporter 2, and prohormone convertases 1/3 and 2. |
| 708 | 11473041 | Other beta-cell transcription factors (e.g., ISL-1, Nkx2.2, and Nkx6.1) were expressed in P. obesus islets, and the DNA binding activity of the insulin transcription factors RIPE3b1-Act and IEF1 was intact. |
| 709 | 11473041 | Ipf1/Pdx1 gene transfer to isolated P. obesus islets normalized the defect in glucose-stimulated insulin gene expression and prevented the rapid depletion of insulin content after exposure to high glucose. |
| 710 | 11473041 | Taken together, these results suggest that the inability of P. obesus islets to adapt to dietary overload, with depletion of insulin content as a consequence, results from IPF1/PDX1 deficiency. |
| 711 | 11473041 | The homeodomain transcription factor IPF1/PDX1 is required in beta-cells for efficient expression of insulin, glucose transporter 2, and prohormone convertases 1/3 and 2. |
| 712 | 11473041 | Other beta-cell transcription factors (e.g., ISL-1, Nkx2.2, and Nkx6.1) were expressed in P. obesus islets, and the DNA binding activity of the insulin transcription factors RIPE3b1-Act and IEF1 was intact. |
| 713 | 11473041 | Ipf1/Pdx1 gene transfer to isolated P. obesus islets normalized the defect in glucose-stimulated insulin gene expression and prevented the rapid depletion of insulin content after exposure to high glucose. |
| 714 | 11473041 | Taken together, these results suggest that the inability of P. obesus islets to adapt to dietary overload, with depletion of insulin content as a consequence, results from IPF1/PDX1 deficiency. |
| 715 | 11473041 | The homeodomain transcription factor IPF1/PDX1 is required in beta-cells for efficient expression of insulin, glucose transporter 2, and prohormone convertases 1/3 and 2. |
| 716 | 11473041 | Other beta-cell transcription factors (e.g., ISL-1, Nkx2.2, and Nkx6.1) were expressed in P. obesus islets, and the DNA binding activity of the insulin transcription factors RIPE3b1-Act and IEF1 was intact. |
| 717 | 11473041 | Ipf1/Pdx1 gene transfer to isolated P. obesus islets normalized the defect in glucose-stimulated insulin gene expression and prevented the rapid depletion of insulin content after exposure to high glucose. |
| 718 | 11473041 | Taken together, these results suggest that the inability of P. obesus islets to adapt to dietary overload, with depletion of insulin content as a consequence, results from IPF1/PDX1 deficiency. |
| 719 | 11554773 | Diabetes is caused either by mutations in the glucokinase gene (glucokinase MODY) or by mutations in transcription factors (transcription factor MODY). |
| 720 | 11554773 | Transcription factor maturity-onset diabetes of the young, caused by mutations in the hepatocyte nuclear factor genes HNF-1alpha, HNF-4alpha and HNF-1beta, and in insulin promoter factor-1 results in a progressive beta-cell defect with increasing treatment requirements and diabetic complications. |
| 721 | 11574405 | Pancreatic duodenal homeobox-1 (PDX-1) is a homeodomain protein that plays an important role in the development of the pancreas and in maintaining the identity and function of the islets of Langerhans. |
| 722 | 11574405 | Glucose and insulin regulate PDX-1 by way of a signaling pathway involving phosphatidylinositol 3-kinase (PI 3-kinase) and SAPK2/p38. |
| 723 | 11574405 | Insulin and sodium arsenite, an activator of the stress-activated pathway, also stimulated PDX-1 movement from the nuclear periphery to the nucleoplasm. |
| 724 | 11574405 | Glucose- and insulin-stimulated translocation of PDX-1 to the nucleoplasm was inhibited by wortmannin and SB 203580, indicating that a pathway involving PI 3-kinase and SAPK2/p38 was involved; translocation was unaffected by PD 098959 and rapamycin, suggesting that neither mitogen-activated protein kinase nor p70(s6k) were involved. |
| 725 | 11574405 | These results demonstrated that PDX-1 shuttles between the nuclear periphery and nucleoplasm in response to changes in glucose and insulin concentrations and that these events are dependent on PI 3-kinase, SAPK2/p38, and a nuclear phosphatase(s). |
| 726 | 11574405 | Pancreatic duodenal homeobox-1 (PDX-1) is a homeodomain protein that plays an important role in the development of the pancreas and in maintaining the identity and function of the islets of Langerhans. |
| 727 | 11574405 | Glucose and insulin regulate PDX-1 by way of a signaling pathway involving phosphatidylinositol 3-kinase (PI 3-kinase) and SAPK2/p38. |
| 728 | 11574405 | Insulin and sodium arsenite, an activator of the stress-activated pathway, also stimulated PDX-1 movement from the nuclear periphery to the nucleoplasm. |
| 729 | 11574405 | Glucose- and insulin-stimulated translocation of PDX-1 to the nucleoplasm was inhibited by wortmannin and SB 203580, indicating that a pathway involving PI 3-kinase and SAPK2/p38 was involved; translocation was unaffected by PD 098959 and rapamycin, suggesting that neither mitogen-activated protein kinase nor p70(s6k) were involved. |
| 730 | 11574405 | These results demonstrated that PDX-1 shuttles between the nuclear periphery and nucleoplasm in response to changes in glucose and insulin concentrations and that these events are dependent on PI 3-kinase, SAPK2/p38, and a nuclear phosphatase(s). |
| 731 | 11574405 | Pancreatic duodenal homeobox-1 (PDX-1) is a homeodomain protein that plays an important role in the development of the pancreas and in maintaining the identity and function of the islets of Langerhans. |
| 732 | 11574405 | Glucose and insulin regulate PDX-1 by way of a signaling pathway involving phosphatidylinositol 3-kinase (PI 3-kinase) and SAPK2/p38. |
| 733 | 11574405 | Insulin and sodium arsenite, an activator of the stress-activated pathway, also stimulated PDX-1 movement from the nuclear periphery to the nucleoplasm. |
| 734 | 11574405 | Glucose- and insulin-stimulated translocation of PDX-1 to the nucleoplasm was inhibited by wortmannin and SB 203580, indicating that a pathway involving PI 3-kinase and SAPK2/p38 was involved; translocation was unaffected by PD 098959 and rapamycin, suggesting that neither mitogen-activated protein kinase nor p70(s6k) were involved. |
| 735 | 11574405 | These results demonstrated that PDX-1 shuttles between the nuclear periphery and nucleoplasm in response to changes in glucose and insulin concentrations and that these events are dependent on PI 3-kinase, SAPK2/p38, and a nuclear phosphatase(s). |
| 736 | 11574405 | Pancreatic duodenal homeobox-1 (PDX-1) is a homeodomain protein that plays an important role in the development of the pancreas and in maintaining the identity and function of the islets of Langerhans. |
| 737 | 11574405 | Glucose and insulin regulate PDX-1 by way of a signaling pathway involving phosphatidylinositol 3-kinase (PI 3-kinase) and SAPK2/p38. |
| 738 | 11574405 | Insulin and sodium arsenite, an activator of the stress-activated pathway, also stimulated PDX-1 movement from the nuclear periphery to the nucleoplasm. |
| 739 | 11574405 | Glucose- and insulin-stimulated translocation of PDX-1 to the nucleoplasm was inhibited by wortmannin and SB 203580, indicating that a pathway involving PI 3-kinase and SAPK2/p38 was involved; translocation was unaffected by PD 098959 and rapamycin, suggesting that neither mitogen-activated protein kinase nor p70(s6k) were involved. |
| 740 | 11574405 | These results demonstrated that PDX-1 shuttles between the nuclear periphery and nucleoplasm in response to changes in glucose and insulin concentrations and that these events are dependent on PI 3-kinase, SAPK2/p38, and a nuclear phosphatase(s). |
| 741 | 11574405 | Pancreatic duodenal homeobox-1 (PDX-1) is a homeodomain protein that plays an important role in the development of the pancreas and in maintaining the identity and function of the islets of Langerhans. |
| 742 | 11574405 | Glucose and insulin regulate PDX-1 by way of a signaling pathway involving phosphatidylinositol 3-kinase (PI 3-kinase) and SAPK2/p38. |
| 743 | 11574405 | Insulin and sodium arsenite, an activator of the stress-activated pathway, also stimulated PDX-1 movement from the nuclear periphery to the nucleoplasm. |
| 744 | 11574405 | Glucose- and insulin-stimulated translocation of PDX-1 to the nucleoplasm was inhibited by wortmannin and SB 203580, indicating that a pathway involving PI 3-kinase and SAPK2/p38 was involved; translocation was unaffected by PD 098959 and rapamycin, suggesting that neither mitogen-activated protein kinase nor p70(s6k) were involved. |
| 745 | 11574405 | These results demonstrated that PDX-1 shuttles between the nuclear periphery and nucleoplasm in response to changes in glucose and insulin concentrations and that these events are dependent on PI 3-kinase, SAPK2/p38, and a nuclear phosphatase(s). |
| 746 | 11590126 | Maturity-onset diabetes of the young (MODY) is a monogenic, autosomal dominant subtype of early-onset diabetes mellitus due to defective insulin secretion by the pancreatic beta-cell in humans. |
| 747 | 11590126 | HNF-4alpha (MODY1), HNF-1alpha (MODY3), IPF-1 (also known as PDX-1, MODY4) and HNF-1beta (MODY5). |
| 748 | 11590126 | Transfection assays with various deletions and mutants of the P2 promoter reveal functional binding sites for HNF-1alpha, HNF-1beta and IPF-1, the other transcription factors known to encode MODY genes. |
| 749 | 11590126 | We demonstrate the significance of this alternative promoter in a large MODY family where a mutated IPF-1 binding site in the P2 promoter of the HNF-4alpha gene co-segregates with diabetes (LOD score 3.25). |
| 750 | 11590126 | Maturity-onset diabetes of the young (MODY) is a monogenic, autosomal dominant subtype of early-onset diabetes mellitus due to defective insulin secretion by the pancreatic beta-cell in humans. |
| 751 | 11590126 | HNF-4alpha (MODY1), HNF-1alpha (MODY3), IPF-1 (also known as PDX-1, MODY4) and HNF-1beta (MODY5). |
| 752 | 11590126 | Transfection assays with various deletions and mutants of the P2 promoter reveal functional binding sites for HNF-1alpha, HNF-1beta and IPF-1, the other transcription factors known to encode MODY genes. |
| 753 | 11590126 | We demonstrate the significance of this alternative promoter in a large MODY family where a mutated IPF-1 binding site in the P2 promoter of the HNF-4alpha gene co-segregates with diabetes (LOD score 3.25). |
| 754 | 11590126 | Maturity-onset diabetes of the young (MODY) is a monogenic, autosomal dominant subtype of early-onset diabetes mellitus due to defective insulin secretion by the pancreatic beta-cell in humans. |
| 755 | 11590126 | HNF-4alpha (MODY1), HNF-1alpha (MODY3), IPF-1 (also known as PDX-1, MODY4) and HNF-1beta (MODY5). |
| 756 | 11590126 | Transfection assays with various deletions and mutants of the P2 promoter reveal functional binding sites for HNF-1alpha, HNF-1beta and IPF-1, the other transcription factors known to encode MODY genes. |
| 757 | 11590126 | We demonstrate the significance of this alternative promoter in a large MODY family where a mutated IPF-1 binding site in the P2 promoter of the HNF-4alpha gene co-segregates with diabetes (LOD score 3.25). |
| 758 | 11679424 | We found decreased steady-state mRNA levels of genes encoding glucose transporter 2 (Glut2), neutral and basic amino acid transporter, liver pyruvate kinase (L-Pk), and insulin in Hnf-1alpha(-/-) mice. |
| 759 | 11679424 | In addition, we determined that the expression of several islet-enriched transcription factors, including Pdx-1, Hnf-4alpha, and Neuro-D1/Beta-2, was reduced in Hnf-1alpha(-/-) mice. |
| 760 | 11679424 | This expression profile was pancreatic islet-specific and distinct from hepatocytes, where we found normal expression of Glut2, L-Pk, and Hnf-4alpha in the liver of Hnf-1alpha(-/-) mice. |
| 761 | 11679424 | The expression of small heterodimer partner (Shp-1), an orphan receptor that can heterodimerize with Hnf-4alpha and inhibit its transcriptional activity, was also reduced in Hnf-1alpha(-/-) islets. |
| 762 | 11679424 | We characterized a 0.58-kb Shp-1 promoter and determined that the decreased expression of Shp-1 may be indirectly mediated by a downregulation of Hnf-4alpha. |
| 763 | 11679424 | We further showed that Shp-1 can repress its own transcriptional activation by inhibiting Hnf-4alpha function, thereby establishing a feedback autoregulatory loop. |
| 764 | 11687580 | Cytokines, such as interleukin-1 beta and interferon-gamma, are putative mediators of immune-induced beta-cell death and, under in vitro conditions, cause beta-cell apoptosis. |
| 765 | 11687580 | We have recently shown that interleukin-1 beta + interferon-gamma modifies the expression of >200 genes in beta-cells. |
| 766 | 11687580 | To identify cytokine-induced and NF-kappa B-regulated genes in primary rat beta-cells, we presently combined two experimental approaches: 1) blocking of NF-kappa B activation in cytokine-exposed beta-cells by a recombinant adenovirus (AdI kappa B((SA)2)) containing an inhibitor of NF-kappa B alpha (I kappa Bac) super-repressor (S32A/S36A) and 2) study of gene expression by microarray analysis. |
| 767 | 11687580 | Cytokine-induced NF-kappa B activation decreased Pdx-1 and increased c-Myc expression. |
| 768 | 11687580 | This, together with NF-kappa B-dependent inhibition of Glut-2, pro-hormone convertase-1, and Isl-1 expression, probably contributes to the loss of differentiated beta-cell functions. |
| 769 | 11692168 | Pancreatic duodenal homeobox-1, PDX-1, a major regulator of beta cell identity and function. |
| 770 | 11692168 | Heterozygous mutations in the gene result in impaired glucose tolerance and symptoms of diabetes as seen in MODY4 and late-onset Type II (non-insulin-dependent) diabetes mellitus. |
| 771 | 11692168 | Defects in pancreatic duodenal homeobox-1 could therefore contribute to Type II diabetes by affecting compensatory mechanisms that increase the rate of beta-cell neogenesis to meet the increased insulin secretory demand. |
| 772 | 11692168 | Pancreatic duodenal homeobox-1, PDX-1, a major regulator of beta cell identity and function. |
| 773 | 11692168 | Heterozygous mutations in the gene result in impaired glucose tolerance and symptoms of diabetes as seen in MODY4 and late-onset Type II (non-insulin-dependent) diabetes mellitus. |
| 774 | 11692168 | Defects in pancreatic duodenal homeobox-1 could therefore contribute to Type II diabetes by affecting compensatory mechanisms that increase the rate of beta-cell neogenesis to meet the increased insulin secretory demand. |
| 775 | 11697865 | We observed an increased mRNA expression of insulin, proendocrine gene neurogenin 3, and beta-cell transcription factor Pdx1 when the cells were grown on bovine collagen I gels. |
| 776 | 11697865 | Application of GIP, GLP-1 derivative NN2211, and activin-A/betacellulin to IMPAN cells in normal culture did not lead to endocrine differentiation. |
| 777 | 11717395 | Mutations in the human genes encoding hepatocyte nuclear factors (HNF) 1alpha, 1beta, 4alpha, and IPF1(PDX1/IDX1/STF1) result in pancreatic beta cell dysfunction and diabetes mellitus. |
| 778 | 11717395 | Hnf1alpha also exerts direct control of pancreatic-specific expression of hnf4gamma and hnf3gamma. |
| 779 | 11717395 | Hnf1alpha dependence of hnf4alpha, hnf4gamma, hnf3gamma, and two previously characterized distal targets (glut2 and pklr) is established only after differentiated cells arise during pancreatic embryonic development. |
| 780 | 11731484 | We further provide evidence that vhnf1 regulates the expression of key patterning genes for these organs. vhnf1 is required for the proper expression of pdx1 and shh (sonic hedgehog) in the gut endoderm, pax2 and wt1 in the pronephric primordial, and valentino (val) in the hindbrain. |
| 781 | 11756345 | Whereas heterozygous mutations in islet-cell transcription factors such as IPF1/IDX-1/STF-1/PDX-1 and NEUROD1/BETA2 serve as a genetic cause of diabetes or glucose intolerance, we investigated the possibility of PAX6 gene mutations being a genetic factor common to aniridia and diabetes. |
| 782 | 11756345 | Oral glucose tolerance tests revealed that all of the patients with a PAX6 gene mutation had glucose intolerance characterized by impaired insulin secretion. |
| 783 | 11776473 | Strategies to increase islet precursor cells from embryonic stem cells include the expression of relevant transcription factors (Pdx1, Ngn3, Isl-1, etc), together with the use of extracellular factors. |
| 784 | 11781323 | Reduction in pancreatic transcription factor PDX-1 impairs glucose-stimulated insulin secretion. |
| 785 | 11781323 | To determine how alterations in PDX-1 affect islet function, we examined insulin secretion and islet physiology in mice with one PDX-1 allele inactivated. |
| 786 | 11781323 | PDX-1(+/-) mice had a normal fasting blood glucose and pancreatic insulin content but had impaired glucose tolerance and secreted less insulin during glucose tolerance testing. |
| 787 | 11781323 | The expression of PDX-1 and glucose transporter 2 in islets from PDX-1(+/-) mice was reduced to 68 and 55%, respectively, whereas glucokinase expression was not significantly altered. |
| 788 | 11781323 | The in situ perfused pancreas of PDX-1(+/-) mice secreted about 45% less insulin when stimulated with 16.7 mm glucose. |
| 789 | 11781323 | The K(m) for insulin release was similar in wild type and PDX-1(+/-) mice. |
| 790 | 11781323 | Insulin secretion in response to 20 mm arginine was unchanged; the response to 10 nm glucagon-like peptide-1 was slightly increased. |
| 791 | 11781323 | These results indicate that a modest reduction in PDX-1 impairs several events in glucose-stimulated insulin secretion (such as NAD(P)H generation, mitochondrial function, and/or mobilization of intracellular Ca(2+)) and that PDX-1 is important for normal function of adult pancreatic islets. |
| 792 | 11781323 | Reduction in pancreatic transcription factor PDX-1 impairs glucose-stimulated insulin secretion. |
| 793 | 11781323 | To determine how alterations in PDX-1 affect islet function, we examined insulin secretion and islet physiology in mice with one PDX-1 allele inactivated. |
| 794 | 11781323 | PDX-1(+/-) mice had a normal fasting blood glucose and pancreatic insulin content but had impaired glucose tolerance and secreted less insulin during glucose tolerance testing. |
| 795 | 11781323 | The expression of PDX-1 and glucose transporter 2 in islets from PDX-1(+/-) mice was reduced to 68 and 55%, respectively, whereas glucokinase expression was not significantly altered. |
| 796 | 11781323 | The in situ perfused pancreas of PDX-1(+/-) mice secreted about 45% less insulin when stimulated with 16.7 mm glucose. |
| 797 | 11781323 | The K(m) for insulin release was similar in wild type and PDX-1(+/-) mice. |
| 798 | 11781323 | Insulin secretion in response to 20 mm arginine was unchanged; the response to 10 nm glucagon-like peptide-1 was slightly increased. |
| 799 | 11781323 | These results indicate that a modest reduction in PDX-1 impairs several events in glucose-stimulated insulin secretion (such as NAD(P)H generation, mitochondrial function, and/or mobilization of intracellular Ca(2+)) and that PDX-1 is important for normal function of adult pancreatic islets. |
| 800 | 11781323 | Reduction in pancreatic transcription factor PDX-1 impairs glucose-stimulated insulin secretion. |
| 801 | 11781323 | To determine how alterations in PDX-1 affect islet function, we examined insulin secretion and islet physiology in mice with one PDX-1 allele inactivated. |
| 802 | 11781323 | PDX-1(+/-) mice had a normal fasting blood glucose and pancreatic insulin content but had impaired glucose tolerance and secreted less insulin during glucose tolerance testing. |
| 803 | 11781323 | The expression of PDX-1 and glucose transporter 2 in islets from PDX-1(+/-) mice was reduced to 68 and 55%, respectively, whereas glucokinase expression was not significantly altered. |
| 804 | 11781323 | The in situ perfused pancreas of PDX-1(+/-) mice secreted about 45% less insulin when stimulated with 16.7 mm glucose. |
| 805 | 11781323 | The K(m) for insulin release was similar in wild type and PDX-1(+/-) mice. |
| 806 | 11781323 | Insulin secretion in response to 20 mm arginine was unchanged; the response to 10 nm glucagon-like peptide-1 was slightly increased. |
| 807 | 11781323 | These results indicate that a modest reduction in PDX-1 impairs several events in glucose-stimulated insulin secretion (such as NAD(P)H generation, mitochondrial function, and/or mobilization of intracellular Ca(2+)) and that PDX-1 is important for normal function of adult pancreatic islets. |
| 808 | 11781323 | Reduction in pancreatic transcription factor PDX-1 impairs glucose-stimulated insulin secretion. |
| 809 | 11781323 | To determine how alterations in PDX-1 affect islet function, we examined insulin secretion and islet physiology in mice with one PDX-1 allele inactivated. |
| 810 | 11781323 | PDX-1(+/-) mice had a normal fasting blood glucose and pancreatic insulin content but had impaired glucose tolerance and secreted less insulin during glucose tolerance testing. |
| 811 | 11781323 | The expression of PDX-1 and glucose transporter 2 in islets from PDX-1(+/-) mice was reduced to 68 and 55%, respectively, whereas glucokinase expression was not significantly altered. |
| 812 | 11781323 | The in situ perfused pancreas of PDX-1(+/-) mice secreted about 45% less insulin when stimulated with 16.7 mm glucose. |
| 813 | 11781323 | The K(m) for insulin release was similar in wild type and PDX-1(+/-) mice. |
| 814 | 11781323 | Insulin secretion in response to 20 mm arginine was unchanged; the response to 10 nm glucagon-like peptide-1 was slightly increased. |
| 815 | 11781323 | These results indicate that a modest reduction in PDX-1 impairs several events in glucose-stimulated insulin secretion (such as NAD(P)H generation, mitochondrial function, and/or mobilization of intracellular Ca(2+)) and that PDX-1 is important for normal function of adult pancreatic islets. |
| 816 | 11781323 | Reduction in pancreatic transcription factor PDX-1 impairs glucose-stimulated insulin secretion. |
| 817 | 11781323 | To determine how alterations in PDX-1 affect islet function, we examined insulin secretion and islet physiology in mice with one PDX-1 allele inactivated. |
| 818 | 11781323 | PDX-1(+/-) mice had a normal fasting blood glucose and pancreatic insulin content but had impaired glucose tolerance and secreted less insulin during glucose tolerance testing. |
| 819 | 11781323 | The expression of PDX-1 and glucose transporter 2 in islets from PDX-1(+/-) mice was reduced to 68 and 55%, respectively, whereas glucokinase expression was not significantly altered. |
| 820 | 11781323 | The in situ perfused pancreas of PDX-1(+/-) mice secreted about 45% less insulin when stimulated with 16.7 mm glucose. |
| 821 | 11781323 | The K(m) for insulin release was similar in wild type and PDX-1(+/-) mice. |
| 822 | 11781323 | Insulin secretion in response to 20 mm arginine was unchanged; the response to 10 nm glucagon-like peptide-1 was slightly increased. |
| 823 | 11781323 | These results indicate that a modest reduction in PDX-1 impairs several events in glucose-stimulated insulin secretion (such as NAD(P)H generation, mitochondrial function, and/or mobilization of intracellular Ca(2+)) and that PDX-1 is important for normal function of adult pancreatic islets. |
| 824 | 11781323 | Reduction in pancreatic transcription factor PDX-1 impairs glucose-stimulated insulin secretion. |
| 825 | 11781323 | To determine how alterations in PDX-1 affect islet function, we examined insulin secretion and islet physiology in mice with one PDX-1 allele inactivated. |
| 826 | 11781323 | PDX-1(+/-) mice had a normal fasting blood glucose and pancreatic insulin content but had impaired glucose tolerance and secreted less insulin during glucose tolerance testing. |
| 827 | 11781323 | The expression of PDX-1 and glucose transporter 2 in islets from PDX-1(+/-) mice was reduced to 68 and 55%, respectively, whereas glucokinase expression was not significantly altered. |
| 828 | 11781323 | The in situ perfused pancreas of PDX-1(+/-) mice secreted about 45% less insulin when stimulated with 16.7 mm glucose. |
| 829 | 11781323 | The K(m) for insulin release was similar in wild type and PDX-1(+/-) mice. |
| 830 | 11781323 | Insulin secretion in response to 20 mm arginine was unchanged; the response to 10 nm glucagon-like peptide-1 was slightly increased. |
| 831 | 11781323 | These results indicate that a modest reduction in PDX-1 impairs several events in glucose-stimulated insulin secretion (such as NAD(P)H generation, mitochondrial function, and/or mobilization of intracellular Ca(2+)) and that PDX-1 is important for normal function of adult pancreatic islets. |
| 832 | 11781323 | Reduction in pancreatic transcription factor PDX-1 impairs glucose-stimulated insulin secretion. |
| 833 | 11781323 | To determine how alterations in PDX-1 affect islet function, we examined insulin secretion and islet physiology in mice with one PDX-1 allele inactivated. |
| 834 | 11781323 | PDX-1(+/-) mice had a normal fasting blood glucose and pancreatic insulin content but had impaired glucose tolerance and secreted less insulin during glucose tolerance testing. |
| 835 | 11781323 | The expression of PDX-1 and glucose transporter 2 in islets from PDX-1(+/-) mice was reduced to 68 and 55%, respectively, whereas glucokinase expression was not significantly altered. |
| 836 | 11781323 | The in situ perfused pancreas of PDX-1(+/-) mice secreted about 45% less insulin when stimulated with 16.7 mm glucose. |
| 837 | 11781323 | The K(m) for insulin release was similar in wild type and PDX-1(+/-) mice. |
| 838 | 11781323 | Insulin secretion in response to 20 mm arginine was unchanged; the response to 10 nm glucagon-like peptide-1 was slightly increased. |
| 839 | 11781323 | These results indicate that a modest reduction in PDX-1 impairs several events in glucose-stimulated insulin secretion (such as NAD(P)H generation, mitochondrial function, and/or mobilization of intracellular Ca(2+)) and that PDX-1 is important for normal function of adult pancreatic islets. |
| 840 | 11799123 | Induction of c-Myc expression suppresses insulin gene transcription by inhibiting NeuroD/BETA2-mediated transcriptional activation. |
| 841 | 11799123 | We have found that hyperglycemia induces the expression of the basic helix-loop-helix transcription factor c-Myc in islets in several different diabetic models. |
| 842 | 11799123 | Adenovirus-mediated c-Myc overexpression suppressed both insulin gene transcription and glucose-stimulated insulin secretion. |
| 843 | 11799123 | Insulin protein content, determined by immunostaining, was markedly decreased in c-Myc-overexpressing cells. |
| 844 | 11799123 | In gel-shift assays c-Myc bound to the E-box in the insulin gene promoter region. |
| 845 | 11799123 | Furthermore, in betaTC1, MIN6, and HIT-T15 cells and primary rat islets, wild type insulin gene promoter activity was dramatically decreased by c-Myc overexpression, whereas the activity of an E-box mutated insulin promoter was not affected. |
| 846 | 11799123 | In HeLa and HepG2 cells c-Myc exerted a suppressive effect on the insulin promoter activity only in the presence of NeuroD/BETA2 but not PDX-1. |
| 847 | 11799123 | Both c-Myc and NeuroD can bind the E-box element in the insulin promoter, but unlike NeuroD, the c-Myc transactivation domain lacked the ability to activate insulin gene expression. |
| 848 | 11799123 | Additionally p300, a co-activator of NeuroD, did not function as a co-activator of c-Myc. |
| 849 | 11799123 | In conclusion, increased expression of c-Myc in beta-cells suppresses the insulin gene transcription by inhibiting NeuroD-mediated transcriptional activation. |
| 850 | 11815473 | Altered beta-cell distribution of pdx-1 and GLUT-2 after a short-term challenge with a high-fat diet in C57BL/6J mice. |
| 851 | 11815473 | However, the nuclear translocation of the homeobox transcription factor, pdx-1, and the plasma membrane translocation of GLUT2 were both impaired in high-fat-fed animals after 1 week. |
| 852 | 11815473 | The early-onset islet dysfunction is accompanied by impaired beta-cell trafficking of two factors, pdx-1 and GLUT-2, which are involved in beta-cell proliferation and glucose recognition. |
| 853 | 11815473 | Altered beta-cell distribution of pdx-1 and GLUT-2 after a short-term challenge with a high-fat diet in C57BL/6J mice. |
| 854 | 11815473 | However, the nuclear translocation of the homeobox transcription factor, pdx-1, and the plasma membrane translocation of GLUT2 were both impaired in high-fat-fed animals after 1 week. |
| 855 | 11815473 | The early-onset islet dysfunction is accompanied by impaired beta-cell trafficking of two factors, pdx-1 and GLUT-2, which are involved in beta-cell proliferation and glucose recognition. |
| 856 | 11815473 | Altered beta-cell distribution of pdx-1 and GLUT-2 after a short-term challenge with a high-fat diet in C57BL/6J mice. |
| 857 | 11815473 | However, the nuclear translocation of the homeobox transcription factor, pdx-1, and the plasma membrane translocation of GLUT2 were both impaired in high-fat-fed animals after 1 week. |
| 858 | 11815473 | The early-onset islet dysfunction is accompanied by impaired beta-cell trafficking of two factors, pdx-1 and GLUT-2, which are involved in beta-cell proliferation and glucose recognition. |
| 859 | 11834421 | Pancreas duodenum homeobox-1 (PDX-1) (also known as insulin promoter factor-1, islet/duodenum homeobox-1, somatostatin transactivating factor-1, insulin upstream factor-1 and glucose-sensitive factor) is a transcription factor encoded by a Hox-like homeodomain gene. |
| 860 | 11834421 | In adult subjects, PDX-1 is essential for normal pancreatic islet function as suggested by its regulatory action on the expression of a number of pancreatic genes, including insulin, somatostatin, islet amyloid polypeptide, the glucose transporter type 2 and glucokinase. |
| 861 | 11834421 | Pancreas duodenum homeobox-1 (PDX-1) (also known as insulin promoter factor-1, islet/duodenum homeobox-1, somatostatin transactivating factor-1, insulin upstream factor-1 and glucose-sensitive factor) is a transcription factor encoded by a Hox-like homeodomain gene. |
| 862 | 11834421 | In adult subjects, PDX-1 is essential for normal pancreatic islet function as suggested by its regulatory action on the expression of a number of pancreatic genes, including insulin, somatostatin, islet amyloid polypeptide, the glucose transporter type 2 and glucokinase. |
| 863 | 11904435 | Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. |
| 864 | 11904435 | In mice, a heterozygous mutation in Pdx-1 alone, but not Hnf-1alpha(+/-), Hnf-3beta(+/-), or Hnf-4alpha(+/-), causes impaired glucose-stimulated insulin secretion in mice. |
| 865 | 11904435 | To investigate the possible functional relationships between these transcription factors on beta-cell activity in vivo, we generated mice with the following combined heterozygous mutations: Pdx-1(+/-)/Hnf-1alpha(+/-), Pdx-1(+/-)/Hnf-3beta(+/-), Pdx-1(+/-)/Hnf-4alpha(+/-), Hnf-1alpha(+/-)/Hnf-4alpha(+/-), and Hnf-3beta(+/-)/Hnf-4alpha(+/-). |
| 866 | 11904435 | The greatest loss in function was in combined heterozygous null alleles of Pdx-1 and Hnf-1alpha (Pdx-1(+/-)/Hnf-1alpha(+/-)), or Pdx-1 and Hnf-3beta (Pdx-1(+/-)/Hnf-3beta(+/-)). |
| 867 | 11904435 | Both double mutants develop progressively impaired glucose tolerance and acquire a compromised first- and second-phase insulin secretion profile in response to glucose compared with Pdx-1(+/-) mice alone. |
| 868 | 11904435 | The loss in beta-cell function in Pdx-1(+/-)/Hnf-3beta(+/-) mice was associated with decreased expression of Nkx-6.1, glucokinase (Gck), aldolase B (aldo-B), and insulin, whereas Nkx2.2, Nkx-6.1, Glut-2, Gck, aldo-B, the liver isoform of pyruvate kinase, and insulin expression was reduced in Pdx-1(+/-)/Hnf-1alpha(+/-) mice. |
| 869 | 11904435 | The islet cell architecture was also abnormal in Pdx-1(+/-)/Hnf-3beta(+/-) and Pdx-1(+/-)/Hnf-1alpha(+/-) mice, with glucagon-expressing cells scattered throughout the islet, a defect that may be connected to decreased E-cadherin expression. |
| 870 | 11904435 | Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. |
| 871 | 11904435 | In mice, a heterozygous mutation in Pdx-1 alone, but not Hnf-1alpha(+/-), Hnf-3beta(+/-), or Hnf-4alpha(+/-), causes impaired glucose-stimulated insulin secretion in mice. |
| 872 | 11904435 | To investigate the possible functional relationships between these transcription factors on beta-cell activity in vivo, we generated mice with the following combined heterozygous mutations: Pdx-1(+/-)/Hnf-1alpha(+/-), Pdx-1(+/-)/Hnf-3beta(+/-), Pdx-1(+/-)/Hnf-4alpha(+/-), Hnf-1alpha(+/-)/Hnf-4alpha(+/-), and Hnf-3beta(+/-)/Hnf-4alpha(+/-). |
| 873 | 11904435 | The greatest loss in function was in combined heterozygous null alleles of Pdx-1 and Hnf-1alpha (Pdx-1(+/-)/Hnf-1alpha(+/-)), or Pdx-1 and Hnf-3beta (Pdx-1(+/-)/Hnf-3beta(+/-)). |
| 874 | 11904435 | Both double mutants develop progressively impaired glucose tolerance and acquire a compromised first- and second-phase insulin secretion profile in response to glucose compared with Pdx-1(+/-) mice alone. |
| 875 | 11904435 | The loss in beta-cell function in Pdx-1(+/-)/Hnf-3beta(+/-) mice was associated with decreased expression of Nkx-6.1, glucokinase (Gck), aldolase B (aldo-B), and insulin, whereas Nkx2.2, Nkx-6.1, Glut-2, Gck, aldo-B, the liver isoform of pyruvate kinase, and insulin expression was reduced in Pdx-1(+/-)/Hnf-1alpha(+/-) mice. |
| 876 | 11904435 | The islet cell architecture was also abnormal in Pdx-1(+/-)/Hnf-3beta(+/-) and Pdx-1(+/-)/Hnf-1alpha(+/-) mice, with glucagon-expressing cells scattered throughout the islet, a defect that may be connected to decreased E-cadherin expression. |
| 877 | 11904435 | Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. |
| 878 | 11904435 | In mice, a heterozygous mutation in Pdx-1 alone, but not Hnf-1alpha(+/-), Hnf-3beta(+/-), or Hnf-4alpha(+/-), causes impaired glucose-stimulated insulin secretion in mice. |
| 879 | 11904435 | To investigate the possible functional relationships between these transcription factors on beta-cell activity in vivo, we generated mice with the following combined heterozygous mutations: Pdx-1(+/-)/Hnf-1alpha(+/-), Pdx-1(+/-)/Hnf-3beta(+/-), Pdx-1(+/-)/Hnf-4alpha(+/-), Hnf-1alpha(+/-)/Hnf-4alpha(+/-), and Hnf-3beta(+/-)/Hnf-4alpha(+/-). |
| 880 | 11904435 | The greatest loss in function was in combined heterozygous null alleles of Pdx-1 and Hnf-1alpha (Pdx-1(+/-)/Hnf-1alpha(+/-)), or Pdx-1 and Hnf-3beta (Pdx-1(+/-)/Hnf-3beta(+/-)). |
| 881 | 11904435 | Both double mutants develop progressively impaired glucose tolerance and acquire a compromised first- and second-phase insulin secretion profile in response to glucose compared with Pdx-1(+/-) mice alone. |
| 882 | 11904435 | The loss in beta-cell function in Pdx-1(+/-)/Hnf-3beta(+/-) mice was associated with decreased expression of Nkx-6.1, glucokinase (Gck), aldolase B (aldo-B), and insulin, whereas Nkx2.2, Nkx-6.1, Glut-2, Gck, aldo-B, the liver isoform of pyruvate kinase, and insulin expression was reduced in Pdx-1(+/-)/Hnf-1alpha(+/-) mice. |
| 883 | 11904435 | The islet cell architecture was also abnormal in Pdx-1(+/-)/Hnf-3beta(+/-) and Pdx-1(+/-)/Hnf-1alpha(+/-) mice, with glucagon-expressing cells scattered throughout the islet, a defect that may be connected to decreased E-cadherin expression. |
| 884 | 11904435 | Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. |
| 885 | 11904435 | In mice, a heterozygous mutation in Pdx-1 alone, but not Hnf-1alpha(+/-), Hnf-3beta(+/-), or Hnf-4alpha(+/-), causes impaired glucose-stimulated insulin secretion in mice. |
| 886 | 11904435 | To investigate the possible functional relationships between these transcription factors on beta-cell activity in vivo, we generated mice with the following combined heterozygous mutations: Pdx-1(+/-)/Hnf-1alpha(+/-), Pdx-1(+/-)/Hnf-3beta(+/-), Pdx-1(+/-)/Hnf-4alpha(+/-), Hnf-1alpha(+/-)/Hnf-4alpha(+/-), and Hnf-3beta(+/-)/Hnf-4alpha(+/-). |
| 887 | 11904435 | The greatest loss in function was in combined heterozygous null alleles of Pdx-1 and Hnf-1alpha (Pdx-1(+/-)/Hnf-1alpha(+/-)), or Pdx-1 and Hnf-3beta (Pdx-1(+/-)/Hnf-3beta(+/-)). |
| 888 | 11904435 | Both double mutants develop progressively impaired glucose tolerance and acquire a compromised first- and second-phase insulin secretion profile in response to glucose compared with Pdx-1(+/-) mice alone. |
| 889 | 11904435 | The loss in beta-cell function in Pdx-1(+/-)/Hnf-3beta(+/-) mice was associated with decreased expression of Nkx-6.1, glucokinase (Gck), aldolase B (aldo-B), and insulin, whereas Nkx2.2, Nkx-6.1, Glut-2, Gck, aldo-B, the liver isoform of pyruvate kinase, and insulin expression was reduced in Pdx-1(+/-)/Hnf-1alpha(+/-) mice. |
| 890 | 11904435 | The islet cell architecture was also abnormal in Pdx-1(+/-)/Hnf-3beta(+/-) and Pdx-1(+/-)/Hnf-1alpha(+/-) mice, with glucagon-expressing cells scattered throughout the islet, a defect that may be connected to decreased E-cadherin expression. |
| 891 | 11904435 | Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. |
| 892 | 11904435 | In mice, a heterozygous mutation in Pdx-1 alone, but not Hnf-1alpha(+/-), Hnf-3beta(+/-), or Hnf-4alpha(+/-), causes impaired glucose-stimulated insulin secretion in mice. |
| 893 | 11904435 | To investigate the possible functional relationships between these transcription factors on beta-cell activity in vivo, we generated mice with the following combined heterozygous mutations: Pdx-1(+/-)/Hnf-1alpha(+/-), Pdx-1(+/-)/Hnf-3beta(+/-), Pdx-1(+/-)/Hnf-4alpha(+/-), Hnf-1alpha(+/-)/Hnf-4alpha(+/-), and Hnf-3beta(+/-)/Hnf-4alpha(+/-). |
| 894 | 11904435 | The greatest loss in function was in combined heterozygous null alleles of Pdx-1 and Hnf-1alpha (Pdx-1(+/-)/Hnf-1alpha(+/-)), or Pdx-1 and Hnf-3beta (Pdx-1(+/-)/Hnf-3beta(+/-)). |
| 895 | 11904435 | Both double mutants develop progressively impaired glucose tolerance and acquire a compromised first- and second-phase insulin secretion profile in response to glucose compared with Pdx-1(+/-) mice alone. |
| 896 | 11904435 | The loss in beta-cell function in Pdx-1(+/-)/Hnf-3beta(+/-) mice was associated with decreased expression of Nkx-6.1, glucokinase (Gck), aldolase B (aldo-B), and insulin, whereas Nkx2.2, Nkx-6.1, Glut-2, Gck, aldo-B, the liver isoform of pyruvate kinase, and insulin expression was reduced in Pdx-1(+/-)/Hnf-1alpha(+/-) mice. |
| 897 | 11904435 | The islet cell architecture was also abnormal in Pdx-1(+/-)/Hnf-3beta(+/-) and Pdx-1(+/-)/Hnf-1alpha(+/-) mice, with glucagon-expressing cells scattered throughout the islet, a defect that may be connected to decreased E-cadherin expression. |
| 898 | 11904435 | Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. |
| 899 | 11904435 | In mice, a heterozygous mutation in Pdx-1 alone, but not Hnf-1alpha(+/-), Hnf-3beta(+/-), or Hnf-4alpha(+/-), causes impaired glucose-stimulated insulin secretion in mice. |
| 900 | 11904435 | To investigate the possible functional relationships between these transcription factors on beta-cell activity in vivo, we generated mice with the following combined heterozygous mutations: Pdx-1(+/-)/Hnf-1alpha(+/-), Pdx-1(+/-)/Hnf-3beta(+/-), Pdx-1(+/-)/Hnf-4alpha(+/-), Hnf-1alpha(+/-)/Hnf-4alpha(+/-), and Hnf-3beta(+/-)/Hnf-4alpha(+/-). |
| 901 | 11904435 | The greatest loss in function was in combined heterozygous null alleles of Pdx-1 and Hnf-1alpha (Pdx-1(+/-)/Hnf-1alpha(+/-)), or Pdx-1 and Hnf-3beta (Pdx-1(+/-)/Hnf-3beta(+/-)). |
| 902 | 11904435 | Both double mutants develop progressively impaired glucose tolerance and acquire a compromised first- and second-phase insulin secretion profile in response to glucose compared with Pdx-1(+/-) mice alone. |
| 903 | 11904435 | The loss in beta-cell function in Pdx-1(+/-)/Hnf-3beta(+/-) mice was associated with decreased expression of Nkx-6.1, glucokinase (Gck), aldolase B (aldo-B), and insulin, whereas Nkx2.2, Nkx-6.1, Glut-2, Gck, aldo-B, the liver isoform of pyruvate kinase, and insulin expression was reduced in Pdx-1(+/-)/Hnf-1alpha(+/-) mice. |
| 904 | 11904435 | The islet cell architecture was also abnormal in Pdx-1(+/-)/Hnf-3beta(+/-) and Pdx-1(+/-)/Hnf-1alpha(+/-) mice, with glucagon-expressing cells scattered throughout the islet, a defect that may be connected to decreased E-cadherin expression. |
| 905 | 11904435 | Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. |
| 906 | 11904435 | In mice, a heterozygous mutation in Pdx-1 alone, but not Hnf-1alpha(+/-), Hnf-3beta(+/-), or Hnf-4alpha(+/-), causes impaired glucose-stimulated insulin secretion in mice. |
| 907 | 11904435 | To investigate the possible functional relationships between these transcription factors on beta-cell activity in vivo, we generated mice with the following combined heterozygous mutations: Pdx-1(+/-)/Hnf-1alpha(+/-), Pdx-1(+/-)/Hnf-3beta(+/-), Pdx-1(+/-)/Hnf-4alpha(+/-), Hnf-1alpha(+/-)/Hnf-4alpha(+/-), and Hnf-3beta(+/-)/Hnf-4alpha(+/-). |
| 908 | 11904435 | The greatest loss in function was in combined heterozygous null alleles of Pdx-1 and Hnf-1alpha (Pdx-1(+/-)/Hnf-1alpha(+/-)), or Pdx-1 and Hnf-3beta (Pdx-1(+/-)/Hnf-3beta(+/-)). |
| 909 | 11904435 | Both double mutants develop progressively impaired glucose tolerance and acquire a compromised first- and second-phase insulin secretion profile in response to glucose compared with Pdx-1(+/-) mice alone. |
| 910 | 11904435 | The loss in beta-cell function in Pdx-1(+/-)/Hnf-3beta(+/-) mice was associated with decreased expression of Nkx-6.1, glucokinase (Gck), aldolase B (aldo-B), and insulin, whereas Nkx2.2, Nkx-6.1, Glut-2, Gck, aldo-B, the liver isoform of pyruvate kinase, and insulin expression was reduced in Pdx-1(+/-)/Hnf-1alpha(+/-) mice. |
| 911 | 11904435 | The islet cell architecture was also abnormal in Pdx-1(+/-)/Hnf-3beta(+/-) and Pdx-1(+/-)/Hnf-1alpha(+/-) mice, with glucagon-expressing cells scattered throughout the islet, a defect that may be connected to decreased E-cadherin expression. |
| 912 | 11912494 | In vitro studies have shown that Pbx1 regulates the activity of Ipf1 (also known as Pdx1), a ParaHox homeodomain transcription factor required for the development and function of the pancreas in mice and humans. |
| 913 | 11912494 | In these embryos, expression of Isl1 and Atoh5, essential regulators of pancreatic morphogenesis and differentiation, was severely reduced. |
| 914 | 11912494 | Analysis of trans-heterozygous Pbx1+/- Ipf1+/- mice revealed in vivo genetic interactions between Pbx1 and Ipf1 that are essential for postnatal pancreatic function; these mice developed age-dependent overt diabetes mellitus, unlike Pbx1+/- or Ipf1+/- mice. |
| 915 | 11912494 | In vitro studies have shown that Pbx1 regulates the activity of Ipf1 (also known as Pdx1), a ParaHox homeodomain transcription factor required for the development and function of the pancreas in mice and humans. |
| 916 | 11912494 | In these embryos, expression of Isl1 and Atoh5, essential regulators of pancreatic morphogenesis and differentiation, was severely reduced. |
| 917 | 11912494 | Analysis of trans-heterozygous Pbx1+/- Ipf1+/- mice revealed in vivo genetic interactions between Pbx1 and Ipf1 that are essential for postnatal pancreatic function; these mice developed age-dependent overt diabetes mellitus, unlike Pbx1+/- or Ipf1+/- mice. |
| 918 | 11914043 | Insulin promotor factor-1 (IPF-1) is a gene critical for pancreatic development and insulin transcription. |
| 919 | 11914736 | The majority of the islet-restricted (BETA2, PDX-1, RIP3b1-Act/C1) and ubiquitous (E2A, HEB) insulin-binding proteins have been characterized. |
| 920 | 11914736 | Their DNA binding activity and their transactivating potency can be modified in response to nutrients (glucose, NEFA) or hormonal stimuli (insulin, leptin, glucagon like peptide-1, growth hormone, prolactin) through kinase-dependent signalling pathways (PI3-K, p38MAPK, PKA, CaMK) modulating their affinities for DNA and/or for each other. |
| 921 | 11924926 | In humans, mutations in leptin, leptin receptor, proopiomelanocortin (POMC), melanocortin-4 receptor (MC4R) and prohormone convertase 1 (PC1) have been described in patients with severe obesity. |
| 922 | 11924926 | Most of these obesity disorders, with the exception of the MC4R mutations, exhibit recessive inheritance and a distinct phenotype with varying degrees of hypothalamic dysfunction, and they unravel the critical role of the central leptin and melanocortin pathways in human appetite control and energy homeostasis. |
| 923 | 11924926 | To date, six MODY genes have been identified, the glucokinase gene and five beta cell-specific transcription factor genes, hepatocyte nuclear factor-1alpha (HNF-1alpha), HNF-1beta, HNF-4alpha, insulin promoter factor-1 (IPF-1) and NeuroD1/BETA2. |
| 924 | 11924926 | At the other end of the spectrum are the inherited syndromes of insulin resistance that are caused by mutations in the insulin receptor gene and in the adipocyte-specific transcription factor PPARgamma. |
| 925 | 11961501 | GLP-1, released from intestinal L-cells, is renowned for its potent stimulation of insulin biosynthesis and release from pancreatic b-cells. |
| 926 | 11961501 | Exogenous administration of GLP-1 to subjects with type 2 diabetes results in the normalization of plasma glucose concentrations, in part, as a result of augmented glucose-stimulated insulin secretion. |
| 927 | 11961501 | GLP-1 also reduces plasma glucose levels by suppressing glucagon secretion from pancreatic a-cells and potentially by improving insulin sensitivity in peripheral tissues. |
| 928 | 11961501 | Further-more, GLP-1 upregulates expression of b-cell genes (GLUT2, glucokinase, insulin, and PDX-1) and promotes b-cell neogenesis and differentiation of ductal cells into insulin secreting cells. |
| 929 | 11978636 | Immature rat intestinal stem cells (IEC-6) given the ability to express the transcription factor, pancreatic duodenal homeobox 1 (Pdx-1), yielded YK cells. |
| 930 | 11978636 | Exposure of YK cells to 2 nmol/l betacellulin yielded BYK cells that showed the presence of insulin expression in cytoplasm and that secreted insulin into culture media. |
| 931 | 11978636 | These results indicated that combined expression of Pdx-1 and Isl-1 in IEC-6 cells was required for the production of insulin. |
| 932 | 11978636 | In fact, overexpression of both Pdx-1 and Isl-1 in IEC-6 cells (Isl-YK-12, -14, and -15 cells) gave them the ability to express insulin without exposure to betacellulin. |
| 933 | 11978636 | In summary, our results indicated that immature intestinal stem cells can differentiate into insulin-producing cells given the ability to express the transcription factors Pdx-1 and Isl-1. |
| 934 | 11978636 | Immature rat intestinal stem cells (IEC-6) given the ability to express the transcription factor, pancreatic duodenal homeobox 1 (Pdx-1), yielded YK cells. |
| 935 | 11978636 | Exposure of YK cells to 2 nmol/l betacellulin yielded BYK cells that showed the presence of insulin expression in cytoplasm and that secreted insulin into culture media. |
| 936 | 11978636 | These results indicated that combined expression of Pdx-1 and Isl-1 in IEC-6 cells was required for the production of insulin. |
| 937 | 11978636 | In fact, overexpression of both Pdx-1 and Isl-1 in IEC-6 cells (Isl-YK-12, -14, and -15 cells) gave them the ability to express insulin without exposure to betacellulin. |
| 938 | 11978636 | In summary, our results indicated that immature intestinal stem cells can differentiate into insulin-producing cells given the ability to express the transcription factors Pdx-1 and Isl-1. |
| 939 | 11978636 | Immature rat intestinal stem cells (IEC-6) given the ability to express the transcription factor, pancreatic duodenal homeobox 1 (Pdx-1), yielded YK cells. |
| 940 | 11978636 | Exposure of YK cells to 2 nmol/l betacellulin yielded BYK cells that showed the presence of insulin expression in cytoplasm and that secreted insulin into culture media. |
| 941 | 11978636 | These results indicated that combined expression of Pdx-1 and Isl-1 in IEC-6 cells was required for the production of insulin. |
| 942 | 11978636 | In fact, overexpression of both Pdx-1 and Isl-1 in IEC-6 cells (Isl-YK-12, -14, and -15 cells) gave them the ability to express insulin without exposure to betacellulin. |
| 943 | 11978636 | In summary, our results indicated that immature intestinal stem cells can differentiate into insulin-producing cells given the ability to express the transcription factors Pdx-1 and Isl-1. |
| 944 | 11978636 | Immature rat intestinal stem cells (IEC-6) given the ability to express the transcription factor, pancreatic duodenal homeobox 1 (Pdx-1), yielded YK cells. |
| 945 | 11978636 | Exposure of YK cells to 2 nmol/l betacellulin yielded BYK cells that showed the presence of insulin expression in cytoplasm and that secreted insulin into culture media. |
| 946 | 11978636 | These results indicated that combined expression of Pdx-1 and Isl-1 in IEC-6 cells was required for the production of insulin. |
| 947 | 11978636 | In fact, overexpression of both Pdx-1 and Isl-1 in IEC-6 cells (Isl-YK-12, -14, and -15 cells) gave them the ability to express insulin without exposure to betacellulin. |
| 948 | 11978636 | In summary, our results indicated that immature intestinal stem cells can differentiate into insulin-producing cells given the ability to express the transcription factors Pdx-1 and Isl-1. |
| 949 | 11979019 | Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of familial diabetes mellitus characterized by early onset, autosomal dominant inheritance and primary defects of insulin secretion. |
| 950 | 11979019 | These genes encode the enzyme glucokinase and the transcription factors hepatocyte nuclear factor 4alpha, hepatocyte nuclear factor 1alpha, insulin promoter factor-1, hepatocyte nuclear factor 1beta and neuroD1. |
| 951 | 11984998 | Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of type 2 diabetes characterised by an early onset, an autosomal dominant inheritance, and a primary defect in insulin secretion. |
| 952 | 11984998 | So far, six MODY genes have been identified (MODY1-6): hepatocyte nuclear factor (HNF-4 alpha), glucokinase, HNF-1 alpha, HNF-1 beta, insulin promoter factor 1(IPF-1), and neurogenic differentiation factor 1 (NEUROD1). |
| 953 | 11984998 | MODY2 and MODY3 are the most common forms of MODY. |
| 954 | 11984998 | In contrast, MODY3 and some of the other MODY forms are characterised by major insulin secretory defects and severe hyperglycaemia associated with microvascular complications. |
| 955 | 11994408 | Pdx1 restores beta cell function in Irs2 knockout mice. |
| 956 | 11994408 | Mutations in Pdx1 or upstream hepatocyte nuclear factors cause autosomal forms of early-onset diabetes (maturity-onset diabetes of the young [MODY]). |
| 957 | 11994408 | In mice, the Irs2 branch of the insulin/Igf signaling system mediates peripheral insulin action and pancreatic beta cell growth and function. |
| 958 | 11994408 | To investigate whether beta cell failure in Irs2(-/-) mice might be related to dysfunction of MODY-related transcription factors, we measured the expression of Pdx1 in islets from young Irs2(-/-) mice. |
| 959 | 11994408 | Before the onset of diabetes, Pdx1 was reduced in islets from Irs2(-/-) mice, whereas it was expressed normally in islets from wild-type or Irs1(-/-) mice, which do not develop diabetes. |
| 960 | 11994408 | Whereas male Irs2(-/-)Pdx1(+/+) mice developed diabetes between 8 and 10 weeks of age, haploinsufficiency for Pdx1 caused diabetes in newborn Irs2(-/-) mice. |
| 961 | 11994408 | By contrast, transgenic expression of Pdx1 restored beta cell mass and function in Irs2(-/-) mice and promoted glucose tolerance throughout life, as these mice survived for at least 20 months without diabetes. |
| 962 | 11994408 | Our results suggest that dysregulation of Pdx1 might represent a common link between ordinary type 2 diabetes and MODY. |
| 963 | 11994408 | Pdx1 restores beta cell function in Irs2 knockout mice. |
| 964 | 11994408 | Mutations in Pdx1 or upstream hepatocyte nuclear factors cause autosomal forms of early-onset diabetes (maturity-onset diabetes of the young [MODY]). |
| 965 | 11994408 | In mice, the Irs2 branch of the insulin/Igf signaling system mediates peripheral insulin action and pancreatic beta cell growth and function. |
| 966 | 11994408 | To investigate whether beta cell failure in Irs2(-/-) mice might be related to dysfunction of MODY-related transcription factors, we measured the expression of Pdx1 in islets from young Irs2(-/-) mice. |
| 967 | 11994408 | Before the onset of diabetes, Pdx1 was reduced in islets from Irs2(-/-) mice, whereas it was expressed normally in islets from wild-type or Irs1(-/-) mice, which do not develop diabetes. |
| 968 | 11994408 | Whereas male Irs2(-/-)Pdx1(+/+) mice developed diabetes between 8 and 10 weeks of age, haploinsufficiency for Pdx1 caused diabetes in newborn Irs2(-/-) mice. |
| 969 | 11994408 | By contrast, transgenic expression of Pdx1 restored beta cell mass and function in Irs2(-/-) mice and promoted glucose tolerance throughout life, as these mice survived for at least 20 months without diabetes. |
| 970 | 11994408 | Our results suggest that dysregulation of Pdx1 might represent a common link between ordinary type 2 diabetes and MODY. |
| 971 | 11994408 | Pdx1 restores beta cell function in Irs2 knockout mice. |
| 972 | 11994408 | Mutations in Pdx1 or upstream hepatocyte nuclear factors cause autosomal forms of early-onset diabetes (maturity-onset diabetes of the young [MODY]). |
| 973 | 11994408 | In mice, the Irs2 branch of the insulin/Igf signaling system mediates peripheral insulin action and pancreatic beta cell growth and function. |
| 974 | 11994408 | To investigate whether beta cell failure in Irs2(-/-) mice might be related to dysfunction of MODY-related transcription factors, we measured the expression of Pdx1 in islets from young Irs2(-/-) mice. |
| 975 | 11994408 | Before the onset of diabetes, Pdx1 was reduced in islets from Irs2(-/-) mice, whereas it was expressed normally in islets from wild-type or Irs1(-/-) mice, which do not develop diabetes. |
| 976 | 11994408 | Whereas male Irs2(-/-)Pdx1(+/+) mice developed diabetes between 8 and 10 weeks of age, haploinsufficiency for Pdx1 caused diabetes in newborn Irs2(-/-) mice. |
| 977 | 11994408 | By contrast, transgenic expression of Pdx1 restored beta cell mass and function in Irs2(-/-) mice and promoted glucose tolerance throughout life, as these mice survived for at least 20 months without diabetes. |
| 978 | 11994408 | Our results suggest that dysregulation of Pdx1 might represent a common link between ordinary type 2 diabetes and MODY. |
| 979 | 11994408 | Pdx1 restores beta cell function in Irs2 knockout mice. |
| 980 | 11994408 | Mutations in Pdx1 or upstream hepatocyte nuclear factors cause autosomal forms of early-onset diabetes (maturity-onset diabetes of the young [MODY]). |
| 981 | 11994408 | In mice, the Irs2 branch of the insulin/Igf signaling system mediates peripheral insulin action and pancreatic beta cell growth and function. |
| 982 | 11994408 | To investigate whether beta cell failure in Irs2(-/-) mice might be related to dysfunction of MODY-related transcription factors, we measured the expression of Pdx1 in islets from young Irs2(-/-) mice. |
| 983 | 11994408 | Before the onset of diabetes, Pdx1 was reduced in islets from Irs2(-/-) mice, whereas it was expressed normally in islets from wild-type or Irs1(-/-) mice, which do not develop diabetes. |
| 984 | 11994408 | Whereas male Irs2(-/-)Pdx1(+/+) mice developed diabetes between 8 and 10 weeks of age, haploinsufficiency for Pdx1 caused diabetes in newborn Irs2(-/-) mice. |
| 985 | 11994408 | By contrast, transgenic expression of Pdx1 restored beta cell mass and function in Irs2(-/-) mice and promoted glucose tolerance throughout life, as these mice survived for at least 20 months without diabetes. |
| 986 | 11994408 | Our results suggest that dysregulation of Pdx1 might represent a common link between ordinary type 2 diabetes and MODY. |
| 987 | 11994408 | Pdx1 restores beta cell function in Irs2 knockout mice. |
| 988 | 11994408 | Mutations in Pdx1 or upstream hepatocyte nuclear factors cause autosomal forms of early-onset diabetes (maturity-onset diabetes of the young [MODY]). |
| 989 | 11994408 | In mice, the Irs2 branch of the insulin/Igf signaling system mediates peripheral insulin action and pancreatic beta cell growth and function. |
| 990 | 11994408 | To investigate whether beta cell failure in Irs2(-/-) mice might be related to dysfunction of MODY-related transcription factors, we measured the expression of Pdx1 in islets from young Irs2(-/-) mice. |
| 991 | 11994408 | Before the onset of diabetes, Pdx1 was reduced in islets from Irs2(-/-) mice, whereas it was expressed normally in islets from wild-type or Irs1(-/-) mice, which do not develop diabetes. |
| 992 | 11994408 | Whereas male Irs2(-/-)Pdx1(+/+) mice developed diabetes between 8 and 10 weeks of age, haploinsufficiency for Pdx1 caused diabetes in newborn Irs2(-/-) mice. |
| 993 | 11994408 | By contrast, transgenic expression of Pdx1 restored beta cell mass and function in Irs2(-/-) mice and promoted glucose tolerance throughout life, as these mice survived for at least 20 months without diabetes. |
| 994 | 11994408 | Our results suggest that dysregulation of Pdx1 might represent a common link between ordinary type 2 diabetes and MODY. |
| 995 | 11994408 | Pdx1 restores beta cell function in Irs2 knockout mice. |
| 996 | 11994408 | Mutations in Pdx1 or upstream hepatocyte nuclear factors cause autosomal forms of early-onset diabetes (maturity-onset diabetes of the young [MODY]). |
| 997 | 11994408 | In mice, the Irs2 branch of the insulin/Igf signaling system mediates peripheral insulin action and pancreatic beta cell growth and function. |
| 998 | 11994408 | To investigate whether beta cell failure in Irs2(-/-) mice might be related to dysfunction of MODY-related transcription factors, we measured the expression of Pdx1 in islets from young Irs2(-/-) mice. |
| 999 | 11994408 | Before the onset of diabetes, Pdx1 was reduced in islets from Irs2(-/-) mice, whereas it was expressed normally in islets from wild-type or Irs1(-/-) mice, which do not develop diabetes. |
| 1000 | 11994408 | Whereas male Irs2(-/-)Pdx1(+/+) mice developed diabetes between 8 and 10 weeks of age, haploinsufficiency for Pdx1 caused diabetes in newborn Irs2(-/-) mice. |
| 1001 | 11994408 | By contrast, transgenic expression of Pdx1 restored beta cell mass and function in Irs2(-/-) mice and promoted glucose tolerance throughout life, as these mice survived for at least 20 months without diabetes. |
| 1002 | 11994408 | Our results suggest that dysregulation of Pdx1 might represent a common link between ordinary type 2 diabetes and MODY. |
| 1003 | 11994408 | Pdx1 restores beta cell function in Irs2 knockout mice. |
| 1004 | 11994408 | Mutations in Pdx1 or upstream hepatocyte nuclear factors cause autosomal forms of early-onset diabetes (maturity-onset diabetes of the young [MODY]). |
| 1005 | 11994408 | In mice, the Irs2 branch of the insulin/Igf signaling system mediates peripheral insulin action and pancreatic beta cell growth and function. |
| 1006 | 11994408 | To investigate whether beta cell failure in Irs2(-/-) mice might be related to dysfunction of MODY-related transcription factors, we measured the expression of Pdx1 in islets from young Irs2(-/-) mice. |
| 1007 | 11994408 | Before the onset of diabetes, Pdx1 was reduced in islets from Irs2(-/-) mice, whereas it was expressed normally in islets from wild-type or Irs1(-/-) mice, which do not develop diabetes. |
| 1008 | 11994408 | Whereas male Irs2(-/-)Pdx1(+/+) mice developed diabetes between 8 and 10 weeks of age, haploinsufficiency for Pdx1 caused diabetes in newborn Irs2(-/-) mice. |
| 1009 | 11994408 | By contrast, transgenic expression of Pdx1 restored beta cell mass and function in Irs2(-/-) mice and promoted glucose tolerance throughout life, as these mice survived for at least 20 months without diabetes. |
| 1010 | 11994408 | Our results suggest that dysregulation of Pdx1 might represent a common link between ordinary type 2 diabetes and MODY. |
| 1011 | 12011047 | Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression. |
| 1012 | 12011047 | In this study, subjecting rat islets to oxidative stress activates JNK, p38 MAPK, and protein kinase C, preceding the decrease of insulin gene expression. |
| 1013 | 12011047 | Adenovirus-mediated overexpression of dominant-negative type (DN) JNK, but not the p38 MAPK inhibitor SB203580 nor the protein kinase C inhibitor GF109203X, protected insulin gene expression and secretion from oxidative stress. |
| 1014 | 12011047 | Moreover, wild type JNK overexpression suppressed both insulin gene expression and secretion. |
| 1015 | 12011047 | These results were correlated with changes in the binding of the important transcription factor PDX-1 to the insulin promoter; adenoviral overexpression of DN-JNK preserved PDX-1 DNA binding activity in the face of oxidative stress, whereas wild type JNK overexpression decreased PDX-1 DNA binding activity. |
| 1016 | 12011047 | In conclusion, activation of JNK is involved in the reduction of insulin gene expression by oxidative stress, and suppression of the JNK pathway protects beta-cells from oxidative stress. |
| 1017 | 12031967 | Overexpression of c-Myc in beta-cells of transgenic mice causes proliferation and apoptosis, downregulation of insulin gene expression, and diabetes. |
| 1018 | 12031967 | To test the hypothesis that c-Myc plays an important role in beta-cell growth and differentiation, we generated transgenic mice overexpressing c-Myc in beta-cells under control of the rat insulin II promoter. |
| 1019 | 12031967 | GLUT2 mRNA was decreased, but other beta-cell-associated genes (IAPP [islet amyloid pancreatic polypeptide], PDX-1 [pancreatic and duodenal homeobox-1], and BETA2/NeuroD) were expressed at near-normal levels. |
| 1020 | 12031967 | Immunostaining for both GLUT2 and Nkx6.1 was mainly cytoplasmic. |
| 1021 | 12031967 | In conclusion, these studies demonstrate that activation of c-Myc in beta-cells leads to 1) increased proliferation and apoptosis, 2) initial hyperplasia with amorphous islet organization, and 3) selective downregulation of insulin gene expression and the development of overt diabetes. |
| 1022 | 12048252 | These differentiated cells can self-assemble to form three-dimensional islet cell-like clusters that express pancreatic islet cell differentiation-related transcripts detectable by reverse transcription-PCR/nested PCR (e.g., PDX-1, PAX-4, PAX-6, Nkx2.2 and Nkx6.1, insulin I, insulin II, glucose transporter 2, and glucagon) and islet-specific hormones detectable by immunocytochemistry (e.g., insulin, glucagon, and pancreatic polypeptide). |
| 1023 | 12049785 | We show here that these cells express islet amyloid polypeptide and prohormone convertase 1/3 (PC1/3), proteins that are not expressed by mature alpha cells, but are found in beta cells. |
| 1024 | 12049785 | PC1/3 converts proglucagon to the functionally distinct hormones glucagon-like peptide (GLP)-1 and GLP-2 rather than glucagon. |
| 1025 | 12049785 | Despite these differences, the early proglucagon-positive cells express, as do mature alpha cells, the POU domain transcription factor Brn-4, and do not express the beta cell factor pdx-1. |
| 1026 | 12085668 | Homozygous mutations of the IPF1/PDX1 (MODY4) and of the Glucokinase (GK, MODY2) genes have been reported. |
| 1027 | 12099699 | The pancreas-specific transcription factor Pdx-1 is important for pancreas development and beta-cell specific gene expression in insulin-producing cells. |
| 1028 | 12099699 | Pdx-1 is also able to bind and activate transcription from the A3 element of the human insulin gene promoter in yeast. |
| 1029 | 12099699 | The pancreas-specific transcription factor Pdx-1 is important for pancreas development and beta-cell specific gene expression in insulin-producing cells. |
| 1030 | 12099699 | Pdx-1 is also able to bind and activate transcription from the A3 element of the human insulin gene promoter in yeast. |
| 1031 | 12124776 | Exendin-4 differentiation of a human pancreatic duct cell line into endocrine cells: involvement of PDX-1 and HNF3beta transcription factors. |
| 1032 | 12124776 | Western blot analysis detected a progressive increase in protein levels of glucokinase and GLUT2 over 3 days of EX-4 treatment. |
| 1033 | 12124776 | We explored the sequence of activation of certain transcription factors known to be essential for the beta cell phenotype: PDX-1, Beta2/NeuroD, and hepatocyte nuclear factor 3beta (HNF3beta). |
| 1034 | 12124776 | Double immunostaining showed that PDX-1 coexisted with insulin and glucagon in EX-4-treated cells. |
| 1035 | 12124776 | EMSA results indicated that EX-4 caused a 12-fold increase in HNF3beta binding to PDX-1 promoter area II. |
| 1036 | 12124776 | Differentiation to insulin-producing cells was also seen when Capan-1 cells were transfected with pdx-1, with 80% of these cells expressing insulin 3 days after transfection. |
| 1037 | 12124776 | During the differentiation of duct cells to endocrine cells, cAMP levels (EX-4 is a ligand for the GLP-1, G-protein coupled receptor) and MAP kinase activity increased. |
| 1038 | 12124776 | Our results indicate that EX-4 activates adenylyl cyclase and MAP kinase which, in turn, may lead to activation of transcription factors necessary for an endocrine phenotype. |
| 1039 | 12124776 | Exendin-4 differentiation of a human pancreatic duct cell line into endocrine cells: involvement of PDX-1 and HNF3beta transcription factors. |
| 1040 | 12124776 | Western blot analysis detected a progressive increase in protein levels of glucokinase and GLUT2 over 3 days of EX-4 treatment. |
| 1041 | 12124776 | We explored the sequence of activation of certain transcription factors known to be essential for the beta cell phenotype: PDX-1, Beta2/NeuroD, and hepatocyte nuclear factor 3beta (HNF3beta). |
| 1042 | 12124776 | Double immunostaining showed that PDX-1 coexisted with insulin and glucagon in EX-4-treated cells. |
| 1043 | 12124776 | EMSA results indicated that EX-4 caused a 12-fold increase in HNF3beta binding to PDX-1 promoter area II. |
| 1044 | 12124776 | Differentiation to insulin-producing cells was also seen when Capan-1 cells were transfected with pdx-1, with 80% of these cells expressing insulin 3 days after transfection. |
| 1045 | 12124776 | During the differentiation of duct cells to endocrine cells, cAMP levels (EX-4 is a ligand for the GLP-1, G-protein coupled receptor) and MAP kinase activity increased. |
| 1046 | 12124776 | Our results indicate that EX-4 activates adenylyl cyclase and MAP kinase which, in turn, may lead to activation of transcription factors necessary for an endocrine phenotype. |
| 1047 | 12124776 | Exendin-4 differentiation of a human pancreatic duct cell line into endocrine cells: involvement of PDX-1 and HNF3beta transcription factors. |
| 1048 | 12124776 | Western blot analysis detected a progressive increase in protein levels of glucokinase and GLUT2 over 3 days of EX-4 treatment. |
| 1049 | 12124776 | We explored the sequence of activation of certain transcription factors known to be essential for the beta cell phenotype: PDX-1, Beta2/NeuroD, and hepatocyte nuclear factor 3beta (HNF3beta). |
| 1050 | 12124776 | Double immunostaining showed that PDX-1 coexisted with insulin and glucagon in EX-4-treated cells. |
| 1051 | 12124776 | EMSA results indicated that EX-4 caused a 12-fold increase in HNF3beta binding to PDX-1 promoter area II. |
| 1052 | 12124776 | Differentiation to insulin-producing cells was also seen when Capan-1 cells were transfected with pdx-1, with 80% of these cells expressing insulin 3 days after transfection. |
| 1053 | 12124776 | During the differentiation of duct cells to endocrine cells, cAMP levels (EX-4 is a ligand for the GLP-1, G-protein coupled receptor) and MAP kinase activity increased. |
| 1054 | 12124776 | Our results indicate that EX-4 activates adenylyl cyclase and MAP kinase which, in turn, may lead to activation of transcription factors necessary for an endocrine phenotype. |
| 1055 | 12124776 | Exendin-4 differentiation of a human pancreatic duct cell line into endocrine cells: involvement of PDX-1 and HNF3beta transcription factors. |
| 1056 | 12124776 | Western blot analysis detected a progressive increase in protein levels of glucokinase and GLUT2 over 3 days of EX-4 treatment. |
| 1057 | 12124776 | We explored the sequence of activation of certain transcription factors known to be essential for the beta cell phenotype: PDX-1, Beta2/NeuroD, and hepatocyte nuclear factor 3beta (HNF3beta). |
| 1058 | 12124776 | Double immunostaining showed that PDX-1 coexisted with insulin and glucagon in EX-4-treated cells. |
| 1059 | 12124776 | EMSA results indicated that EX-4 caused a 12-fold increase in HNF3beta binding to PDX-1 promoter area II. |
| 1060 | 12124776 | Differentiation to insulin-producing cells was also seen when Capan-1 cells were transfected with pdx-1, with 80% of these cells expressing insulin 3 days after transfection. |
| 1061 | 12124776 | During the differentiation of duct cells to endocrine cells, cAMP levels (EX-4 is a ligand for the GLP-1, G-protein coupled receptor) and MAP kinase activity increased. |
| 1062 | 12124776 | Our results indicate that EX-4 activates adenylyl cyclase and MAP kinase which, in turn, may lead to activation of transcription factors necessary for an endocrine phenotype. |
| 1063 | 12124776 | Exendin-4 differentiation of a human pancreatic duct cell line into endocrine cells: involvement of PDX-1 and HNF3beta transcription factors. |
| 1064 | 12124776 | Western blot analysis detected a progressive increase in protein levels of glucokinase and GLUT2 over 3 days of EX-4 treatment. |
| 1065 | 12124776 | We explored the sequence of activation of certain transcription factors known to be essential for the beta cell phenotype: PDX-1, Beta2/NeuroD, and hepatocyte nuclear factor 3beta (HNF3beta). |
| 1066 | 12124776 | Double immunostaining showed that PDX-1 coexisted with insulin and glucagon in EX-4-treated cells. |
| 1067 | 12124776 | EMSA results indicated that EX-4 caused a 12-fold increase in HNF3beta binding to PDX-1 promoter area II. |
| 1068 | 12124776 | Differentiation to insulin-producing cells was also seen when Capan-1 cells were transfected with pdx-1, with 80% of these cells expressing insulin 3 days after transfection. |
| 1069 | 12124776 | During the differentiation of duct cells to endocrine cells, cAMP levels (EX-4 is a ligand for the GLP-1, G-protein coupled receptor) and MAP kinase activity increased. |
| 1070 | 12124776 | Our results indicate that EX-4 activates adenylyl cyclase and MAP kinase which, in turn, may lead to activation of transcription factors necessary for an endocrine phenotype. |
| 1071 | 12145164 | PDX-1 induces differentiation of intestinal epithelioid IEC-6 into insulin-producing cells. |
| 1072 | 12145164 | By exogenous expression of the PDX-1 gene, IEC-6 cells started expressing multiple beta-cell-specific genes such as amylin, glucokinase, and Nkx6.1, which were not found in the original IEC-6 cells. |
| 1073 | 12145164 | Insulin gene expression, which was missing initially even in the PDX-1-transfected IEC-6 cells, became detectable when the cells were transplanted under the renal capsule of a rat. |
| 1074 | 12145164 | When the PDX-1(+) IEC-6 cells were kept in vitro, treatment with betacellulin could also confer insulin gene expression to them. |
| 1075 | 12145164 | The in vivo or in vitro inductions of the insulin gene expression were not observed in the PDX-1(-) IEC-6 cells. |
| 1076 | 12145164 | PDX-1 induces differentiation of intestinal epithelioid IEC-6 into insulin-producing cells. |
| 1077 | 12145164 | By exogenous expression of the PDX-1 gene, IEC-6 cells started expressing multiple beta-cell-specific genes such as amylin, glucokinase, and Nkx6.1, which were not found in the original IEC-6 cells. |
| 1078 | 12145164 | Insulin gene expression, which was missing initially even in the PDX-1-transfected IEC-6 cells, became detectable when the cells were transplanted under the renal capsule of a rat. |
| 1079 | 12145164 | When the PDX-1(+) IEC-6 cells were kept in vitro, treatment with betacellulin could also confer insulin gene expression to them. |
| 1080 | 12145164 | The in vivo or in vitro inductions of the insulin gene expression were not observed in the PDX-1(-) IEC-6 cells. |
| 1081 | 12145164 | PDX-1 induces differentiation of intestinal epithelioid IEC-6 into insulin-producing cells. |
| 1082 | 12145164 | By exogenous expression of the PDX-1 gene, IEC-6 cells started expressing multiple beta-cell-specific genes such as amylin, glucokinase, and Nkx6.1, which were not found in the original IEC-6 cells. |
| 1083 | 12145164 | Insulin gene expression, which was missing initially even in the PDX-1-transfected IEC-6 cells, became detectable when the cells were transplanted under the renal capsule of a rat. |
| 1084 | 12145164 | When the PDX-1(+) IEC-6 cells were kept in vitro, treatment with betacellulin could also confer insulin gene expression to them. |
| 1085 | 12145164 | The in vivo or in vitro inductions of the insulin gene expression were not observed in the PDX-1(-) IEC-6 cells. |
| 1086 | 12145164 | PDX-1 induces differentiation of intestinal epithelioid IEC-6 into insulin-producing cells. |
| 1087 | 12145164 | By exogenous expression of the PDX-1 gene, IEC-6 cells started expressing multiple beta-cell-specific genes such as amylin, glucokinase, and Nkx6.1, which were not found in the original IEC-6 cells. |
| 1088 | 12145164 | Insulin gene expression, which was missing initially even in the PDX-1-transfected IEC-6 cells, became detectable when the cells were transplanted under the renal capsule of a rat. |
| 1089 | 12145164 | When the PDX-1(+) IEC-6 cells were kept in vitro, treatment with betacellulin could also confer insulin gene expression to them. |
| 1090 | 12145164 | The in vivo or in vitro inductions of the insulin gene expression were not observed in the PDX-1(-) IEC-6 cells. |
| 1091 | 12145164 | PDX-1 induces differentiation of intestinal epithelioid IEC-6 into insulin-producing cells. |
| 1092 | 12145164 | By exogenous expression of the PDX-1 gene, IEC-6 cells started expressing multiple beta-cell-specific genes such as amylin, glucokinase, and Nkx6.1, which were not found in the original IEC-6 cells. |
| 1093 | 12145164 | Insulin gene expression, which was missing initially even in the PDX-1-transfected IEC-6 cells, became detectable when the cells were transplanted under the renal capsule of a rat. |
| 1094 | 12145164 | When the PDX-1(+) IEC-6 cells were kept in vitro, treatment with betacellulin could also confer insulin gene expression to them. |
| 1095 | 12145164 | The in vivo or in vitro inductions of the insulin gene expression were not observed in the PDX-1(-) IEC-6 cells. |
| 1096 | 12145169 | Foxa2 controls Pdx1 gene expression in pancreatic beta-cells in vivo. |
| 1097 | 12145169 | Prior in vitro analysis has suggested that the forkhead/winged helix transcription factor Foxa2 (formerly HNF-3beta) is a major upstream regulator of Pdx1, a homeobox gene essential for pancreatic development. |
| 1098 | 12145169 | To analyze the Foxa2/Pdx1 regulatory cascade during pancreatic beta-cell differentiation, we used conditional gene ablation of Foxa2 in mice. |
| 1099 | 12145169 | We demonstrated that the deletion of Foxa2 in beta-cell-specific knockout mice results in downregulation of Pdx1 mRNA and subsequent reduction of PDX-1 protein levels in islets. |
| 1100 | 12145169 | These data represent the first in vivo demonstration that Foxa2 acts upstream of Pdx1 in the differentiated beta-cell. |
| 1101 | 12145169 | Foxa2 controls Pdx1 gene expression in pancreatic beta-cells in vivo. |
| 1102 | 12145169 | Prior in vitro analysis has suggested that the forkhead/winged helix transcription factor Foxa2 (formerly HNF-3beta) is a major upstream regulator of Pdx1, a homeobox gene essential for pancreatic development. |
| 1103 | 12145169 | To analyze the Foxa2/Pdx1 regulatory cascade during pancreatic beta-cell differentiation, we used conditional gene ablation of Foxa2 in mice. |
| 1104 | 12145169 | We demonstrated that the deletion of Foxa2 in beta-cell-specific knockout mice results in downregulation of Pdx1 mRNA and subsequent reduction of PDX-1 protein levels in islets. |
| 1105 | 12145169 | These data represent the first in vivo demonstration that Foxa2 acts upstream of Pdx1 in the differentiated beta-cell. |
| 1106 | 12145169 | Foxa2 controls Pdx1 gene expression in pancreatic beta-cells in vivo. |
| 1107 | 12145169 | Prior in vitro analysis has suggested that the forkhead/winged helix transcription factor Foxa2 (formerly HNF-3beta) is a major upstream regulator of Pdx1, a homeobox gene essential for pancreatic development. |
| 1108 | 12145169 | To analyze the Foxa2/Pdx1 regulatory cascade during pancreatic beta-cell differentiation, we used conditional gene ablation of Foxa2 in mice. |
| 1109 | 12145169 | We demonstrated that the deletion of Foxa2 in beta-cell-specific knockout mice results in downregulation of Pdx1 mRNA and subsequent reduction of PDX-1 protein levels in islets. |
| 1110 | 12145169 | These data represent the first in vivo demonstration that Foxa2 acts upstream of Pdx1 in the differentiated beta-cell. |
| 1111 | 12145169 | Foxa2 controls Pdx1 gene expression in pancreatic beta-cells in vivo. |
| 1112 | 12145169 | Prior in vitro analysis has suggested that the forkhead/winged helix transcription factor Foxa2 (formerly HNF-3beta) is a major upstream regulator of Pdx1, a homeobox gene essential for pancreatic development. |
| 1113 | 12145169 | To analyze the Foxa2/Pdx1 regulatory cascade during pancreatic beta-cell differentiation, we used conditional gene ablation of Foxa2 in mice. |
| 1114 | 12145169 | We demonstrated that the deletion of Foxa2 in beta-cell-specific knockout mice results in downregulation of Pdx1 mRNA and subsequent reduction of PDX-1 protein levels in islets. |
| 1115 | 12145169 | These data represent the first in vivo demonstration that Foxa2 acts upstream of Pdx1 in the differentiated beta-cell. |
| 1116 | 12145169 | Foxa2 controls Pdx1 gene expression in pancreatic beta-cells in vivo. |
| 1117 | 12145169 | Prior in vitro analysis has suggested that the forkhead/winged helix transcription factor Foxa2 (formerly HNF-3beta) is a major upstream regulator of Pdx1, a homeobox gene essential for pancreatic development. |
| 1118 | 12145169 | To analyze the Foxa2/Pdx1 regulatory cascade during pancreatic beta-cell differentiation, we used conditional gene ablation of Foxa2 in mice. |
| 1119 | 12145169 | We demonstrated that the deletion of Foxa2 in beta-cell-specific knockout mice results in downregulation of Pdx1 mRNA and subsequent reduction of PDX-1 protein levels in islets. |
| 1120 | 12145169 | These data represent the first in vivo demonstration that Foxa2 acts upstream of Pdx1 in the differentiated beta-cell. |
| 1121 | 12150938 | PDX-1 mediates glucose responsiveness of GAD(67), but not GAD(65), gene transcription in islets of Langerhans. |
| 1122 | 12150938 | Glucose-regulated transcription of the insulin gene is in part mediated via the homeobox transcription factor PDX-1. |
| 1123 | 12150938 | We have studied the mRNA level of two isoforms of GAD, GAD(65) and GAD(67), and found that GAD(67) but not GAD(65) mRNA steady-state level is regulated by glucose. |
| 1124 | 12150938 | We show that PDX-1 is able to bind to two TAAT-boxes in the GAD(67) promoter and that functional disruption of these two PDX-1 binding elements has an additive effect in severely impairing glucose responsiveness of the GAD(67) promoter. |
| 1125 | 12150938 | These data strongly suggest that PDX-1 is involved in glucose-regulated expression of GAD(67). |
| 1126 | 12150938 | PDX-1 mediates glucose responsiveness of GAD(67), but not GAD(65), gene transcription in islets of Langerhans. |
| 1127 | 12150938 | Glucose-regulated transcription of the insulin gene is in part mediated via the homeobox transcription factor PDX-1. |
| 1128 | 12150938 | We have studied the mRNA level of two isoforms of GAD, GAD(65) and GAD(67), and found that GAD(67) but not GAD(65) mRNA steady-state level is regulated by glucose. |
| 1129 | 12150938 | We show that PDX-1 is able to bind to two TAAT-boxes in the GAD(67) promoter and that functional disruption of these two PDX-1 binding elements has an additive effect in severely impairing glucose responsiveness of the GAD(67) promoter. |
| 1130 | 12150938 | These data strongly suggest that PDX-1 is involved in glucose-regulated expression of GAD(67). |
| 1131 | 12150938 | PDX-1 mediates glucose responsiveness of GAD(67), but not GAD(65), gene transcription in islets of Langerhans. |
| 1132 | 12150938 | Glucose-regulated transcription of the insulin gene is in part mediated via the homeobox transcription factor PDX-1. |
| 1133 | 12150938 | We have studied the mRNA level of two isoforms of GAD, GAD(65) and GAD(67), and found that GAD(67) but not GAD(65) mRNA steady-state level is regulated by glucose. |
| 1134 | 12150938 | We show that PDX-1 is able to bind to two TAAT-boxes in the GAD(67) promoter and that functional disruption of these two PDX-1 binding elements has an additive effect in severely impairing glucose responsiveness of the GAD(67) promoter. |
| 1135 | 12150938 | These data strongly suggest that PDX-1 is involved in glucose-regulated expression of GAD(67). |
| 1136 | 12150938 | PDX-1 mediates glucose responsiveness of GAD(67), but not GAD(65), gene transcription in islets of Langerhans. |
| 1137 | 12150938 | Glucose-regulated transcription of the insulin gene is in part mediated via the homeobox transcription factor PDX-1. |
| 1138 | 12150938 | We have studied the mRNA level of two isoforms of GAD, GAD(65) and GAD(67), and found that GAD(67) but not GAD(65) mRNA steady-state level is regulated by glucose. |
| 1139 | 12150938 | We show that PDX-1 is able to bind to two TAAT-boxes in the GAD(67) promoter and that functional disruption of these two PDX-1 binding elements has an additive effect in severely impairing glucose responsiveness of the GAD(67) promoter. |
| 1140 | 12150938 | These data strongly suggest that PDX-1 is involved in glucose-regulated expression of GAD(67). |
| 1141 | 12173691 | Maturity-onset diabetes of the young (MODY) is a genetic subgroup of diabetes characterised by an autosomal dominant inheritance and early onset, non-insulin dependent diabetes. |
| 1142 | 12173691 | Patients with mutation in genes encoding the transcription factors, hepatocyte nuclear factor (HNF)- 1alpha, HNF-4alpha, HNF-1beta and insulin promoter factor 1 (IPF-1) have a common progressive beta-cell failure resulting in increasing hyperglycaemia and treatment requirements. |
| 1143 | 12173691 | Patients with transcription factor mutations have a range of discrete extra-pancreatic phenotypes including a low renal threshold for glucose with HNF-1alpha mutations, altered lipids and lipoproteins with HNF-4alpha mutations and a variety of cystic renal diseases and uterine and genital developmental disorders with HNF-1beta mutations. |
| 1144 | 12193532 | P. obesus islets do not increase proinsulin gene expression when exposed to high glucose, which may be related to absence of the conserved form of the transcription factor insulin promoter factor 1/pancreatic-duodenal homeobox 1. |
| 1145 | 12193564 | The incretin hormones glucagon-like peptide 1 (GLP-1) and cholecystokinin (CCK) are known to be released from the gut in response to oral feeding and enhance insulin secretion from pancreatic beta-cells. |
| 1146 | 12193564 | We exposed fetal pig islet-like cell clusters (ICCs) to 100 nM GLP-1, 5 micro M CCK, or 10 mM nicotinamide (NIC; a positive control) for 6 h and demonstrated 3- and 1.7-fold increases in glucose-induced insulin secretion for GLP-1 and CCK, respectively. |
| 1147 | 12193564 | However, exposure for 4 d enhanced formation of beta-cells from undifferentiated cells, from 8 +/- 1% (controls) to 17 +/- 3% for GLP-1, 20 +/- 4% for CCK, and 15 +/- 1 for NIC (P < 0.001). |
| 1148 | 12193564 | ICCs exposed to GLP-1 for 3 d also showed a 1.9-fold increase in the intensity of PDX-1(+) cells, as assessed by semiquantitative fluorescent immunocytochemistry. |
| 1149 | 12193564 | Perfusion of these grafts at 2 months showed that ICCs previously exposed to GLP-1, CCK, and NIC (but not controls), were functional and mature. |
| 1150 | 12193564 | In conclusion, GLP-1 and CCK have a dual effect on fetal pig ICCs, causing maturation of glucose-induced insulin secretion from beta-cells as well as enhancement of differentiation from undifferentiated precursors. |
| 1151 | 12193567 | Transfection of pancreatic-derived beta-cells with a minigene encoding for human glucagon-like peptide-1 regulates glucose-dependent insulin synthesis and secretion. |
| 1152 | 12193567 | Glucagon-like peptide-1 (GLP-1) is an incretin hormone derived from the proglucagon gene, capable of regulating the transcription of the three major genes that determine the pancreatic beta-cell-specific phenotype: insulin, GLUT-2, and glucokinase. |
| 1153 | 12193567 | Two constructs were generated: In one, the expression of GLP-1 was under the control of the cytomegalovirus (CMV) promoter (CMV/GLP-1), and the second was regulated by the rat insulin II promoter (RIP)/GLP-1). |
| 1154 | 12193567 | Gene expression studies revealed that although CMV/GLP-1 cells did not gain a greater glucose sensitivity as a result of the transfection with GLP-1, compared with cells transfected with the plasmid alone, RIP/GLP-1 was capable of regulating the gene expression of insulin and GLP-1 based on the concentration of glucose in the culture medium. |
| 1155 | 12193567 | Detection of the counterpart proteins (insulin and GLP-1) in the culture medium paralleled the observation derived from the Northern blot analysis. |
| 1156 | 12193567 | GLP-1 action was mediated by an IDX-1 (islet/duodenum homeobox-1) dependent transactivation of the endogenous insulin promoter, as demonstrated by gel shift analysis. |
| 1157 | 12193567 | This was further suggested by a significant increase of the glucose-dependent binding of IDX-1 to the insulin promoter in RIP/GLP-1 cells but not in CMV/GLP-1 cells or control cells. |
| 1158 | 12193567 | Finally, we observed that although the GLP-1-dependent secretion of insulin was mediated by an increase in cAMP levels, the transcription of the insulin gene, in response to GLP-1, was in large part cAMP independent. |
| 1159 | 12193567 | Transfection of pancreatic-derived beta-cells with a minigene encoding for human glucagon-like peptide-1 regulates glucose-dependent insulin synthesis and secretion. |
| 1160 | 12193567 | Glucagon-like peptide-1 (GLP-1) is an incretin hormone derived from the proglucagon gene, capable of regulating the transcription of the three major genes that determine the pancreatic beta-cell-specific phenotype: insulin, GLUT-2, and glucokinase. |
| 1161 | 12193567 | Two constructs were generated: In one, the expression of GLP-1 was under the control of the cytomegalovirus (CMV) promoter (CMV/GLP-1), and the second was regulated by the rat insulin II promoter (RIP)/GLP-1). |
| 1162 | 12193567 | Gene expression studies revealed that although CMV/GLP-1 cells did not gain a greater glucose sensitivity as a result of the transfection with GLP-1, compared with cells transfected with the plasmid alone, RIP/GLP-1 was capable of regulating the gene expression of insulin and GLP-1 based on the concentration of glucose in the culture medium. |
| 1163 | 12193567 | Detection of the counterpart proteins (insulin and GLP-1) in the culture medium paralleled the observation derived from the Northern blot analysis. |
| 1164 | 12193567 | GLP-1 action was mediated by an IDX-1 (islet/duodenum homeobox-1) dependent transactivation of the endogenous insulin promoter, as demonstrated by gel shift analysis. |
| 1165 | 12193567 | This was further suggested by a significant increase of the glucose-dependent binding of IDX-1 to the insulin promoter in RIP/GLP-1 cells but not in CMV/GLP-1 cells or control cells. |
| 1166 | 12193567 | Finally, we observed that although the GLP-1-dependent secretion of insulin was mediated by an increase in cAMP levels, the transcription of the insulin gene, in response to GLP-1, was in large part cAMP independent. |
| 1167 | 12203996 | Several genes are known to induce MODY : HNF4A/MODY1, GCK/MODY2, TCF1/MODY3, IPF1/MODY4, TCF2/MODY5 and NEUROD1/MODY6. |
| 1168 | 12219087 | Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. |
| 1169 | 12219087 | We show that haploinsufficiency of the Foxo1 gene, encoding a forkhead transcription factor (forkhead box transcription factor O1), restores insulin sensitivity and rescues the diabetic phenotype in insulin-resistant mice by reducing hepatic expression of glucogenetic genes and increasing adipocyte expression of insulin-sensitizing genes. |
| 1170 | 12219087 | Conversely, a gain-of-function Foxo1 mutation targeted to liver and pancreatic beta-cells results in diabetes arising from a combination of increased hepatic glucose production and impaired beta-cell compensation due to decreased Pdx1 expression. |
| 1171 | 12219087 | These data indicate that Foxo1 is a negative regulator of insulin sensitivity in liver, adipocytes and pancreatic beta-cells. |
| 1172 | 12219087 | Impaired insulin signaling to Foxo1 provides a unifying mechanism for the common metabolic abnormalities of type 2 diabetes.NOTE: In the AOP version of this article, the name of the fourth author was misspelled as W K Cavanee rather than the correct spelling: W K Cavenee. |
| 1173 | 12242483 | Immunohistochemically, small cells are positive for PDX-1, synaptophysin, insulin, glucagon, somatostatin, pancreatic polypeptide, alpha-fetaprotein and Bcl-2 and negative for cytokeratin 19 and nestin. |
| 1174 | 12323111 | The failure of glucose-stimulated insulin secretion (GSIS) in beta cells helps to sustain the elevations of serum glucose and free fatty acids, which in turn reinforce the failure of GSIS, possibly by inhibiting expression of the transcription factor IDX-1; NIDDM thus represents a vicious cycle that is not easily broken. |
| 1175 | 12323111 | Long-lived analogs of glucagon-like peptide-1 (GLP-1) may find a key role in BRT; this incretin hormone not only potentiates GSIS, but also appears to increase the expression and activity of IDX-1 in beta cells, thus promoting beta cell redifferentiation. |
| 1176 | 12323111 | The failure of glucose-stimulated insulin secretion (GSIS) in beta cells helps to sustain the elevations of serum glucose and free fatty acids, which in turn reinforce the failure of GSIS, possibly by inhibiting expression of the transcription factor IDX-1; NIDDM thus represents a vicious cycle that is not easily broken. |
| 1177 | 12323111 | Long-lived analogs of glucagon-like peptide-1 (GLP-1) may find a key role in BRT; this incretin hormone not only potentiates GSIS, but also appears to increase the expression and activity of IDX-1 in beta cells, thus promoting beta cell redifferentiation. |
| 1178 | 12438314 | At the same time points, high hyperglycemia rats showed a global alteration in gene expression with decreased mRNA for insulin, IAPP, islet-associated transcription factors (pancreatic and duodenal homeobox-1, BETA2/NeuroD, Nkx6.1, and hepatocyte nuclear factor 1 alpha), beta-cell metabolic enzymes (glucose transporter 2, glucokinase, mitochondrial glycerol phosphate dehydrogenase, and pyruvate carboxylase), and ion channels/pumps (Kir6.2, VDCC beta, and sarcoplasmic reticulum Ca(2+)-ATPase 3). |
| 1179 | 12438314 | Conversely, genes normally suppressed in beta-cells, such as lactate dehydrogenase-A, hexokinase I, glucose-6-phosphatase, stress genes (heme oxygenase-1, A20, and Fas), and the transcription factor c-Myc, were markedly increased. |
| 1180 | 12473241 | Insulin is a predominant autoantigen in IDDM in man and the NOD mouse. |
| 1181 | 12473241 | None of the known pancreatic transcription factors for insulin; Pdx-1, Pax6 or Nkx6.1 were detectable in the thymus of Balb/c mice. |
| 1182 | 12473241 | These results support the idea that low insulin expression in the thymus may be a predisposing cause for development of diabetes in NOD mice analogous with what has been found in humans with the disease-disposing IDDM2 allele. |
| 1183 | 12475770 | The homeodomain-containing transcription factor pancreatic duodenal homeobox 1 (PDX-1) plays a key role in pancreas development and in beta-cell function. |
| 1184 | 12475770 | A number of transcription factors binding to and modulating the transcriptional activity of the regulatory elements were identified, such as hepatocyte nuclear factor (HNF)-3beta, HNF-1alpha, SP1/3, and, interestingly, PDX-1 itself. |
| 1185 | 12475770 | The homeodomain-containing transcription factor pancreatic duodenal homeobox 1 (PDX-1) plays a key role in pancreas development and in beta-cell function. |
| 1186 | 12475770 | A number of transcription factors binding to and modulating the transcriptional activity of the regulatory elements were identified, such as hepatocyte nuclear factor (HNF)-3beta, HNF-1alpha, SP1/3, and, interestingly, PDX-1 itself. |
| 1187 | 12475772 | Except for MODY2 (glucokinase), all other MODY subtypes have been linked to transcription factors. |
| 1188 | 12475772 | The existence of a regulatory circuit between HNF-4alpha and HNF-1alpha is confirmed in these cell models. |
| 1189 | 12475772 | The MODY4 gene, IPF-1 (insulin promoter factor-1)/PDX-1 (pancreas duodenum homeobox-1), controls not only the transcription of insulin but also expression of enzymes involved in its processing. |
| 1190 | 12475772 | Suppression of Pdx-1 function in INS-1 cells does not alter glucose metabolism but rather inhibits insulin release by impairing steps distal to the generation of mitochondrial coupling factors. |
| 1191 | 12475772 | Except for MODY2 (glucokinase), all other MODY subtypes have been linked to transcription factors. |
| 1192 | 12475772 | The existence of a regulatory circuit between HNF-4alpha and HNF-1alpha is confirmed in these cell models. |
| 1193 | 12475772 | The MODY4 gene, IPF-1 (insulin promoter factor-1)/PDX-1 (pancreas duodenum homeobox-1), controls not only the transcription of insulin but also expression of enzymes involved in its processing. |
| 1194 | 12475772 | Suppression of Pdx-1 function in INS-1 cells does not alter glucose metabolism but rather inhibits insulin release by impairing steps distal to the generation of mitochondrial coupling factors. |
| 1195 | 12488434 | The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. |
| 1196 | 12488434 | We report that haploinsufficiency for the forkhead transcription factor Foxo1 reverses beta cell failure in Irs2(-/-) mice through partial restoration of beta cell proliferation and increased expression of the pancreatic transcription factor pancreas/duodenum homeobox gene-1 (Pdx1). |
| 1197 | 12488434 | Foxo1 and Pdx1 exhibit mutually exclusive patterns of nuclear localization in beta cells, and constitutive nuclear expression of a mutant Foxo1 is associated with lack of Pdx1 expression. |
| 1198 | 12488434 | We show that Foxo1 acts as a repressor of Foxa2-dependent (Hnf-3beta-dependent) expression from the Pdx1 promoter. |
| 1199 | 12488434 | We propose that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts. |
| 1200 | 12488434 | The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. |
| 1201 | 12488434 | We report that haploinsufficiency for the forkhead transcription factor Foxo1 reverses beta cell failure in Irs2(-/-) mice through partial restoration of beta cell proliferation and increased expression of the pancreatic transcription factor pancreas/duodenum homeobox gene-1 (Pdx1). |
| 1202 | 12488434 | Foxo1 and Pdx1 exhibit mutually exclusive patterns of nuclear localization in beta cells, and constitutive nuclear expression of a mutant Foxo1 is associated with lack of Pdx1 expression. |
| 1203 | 12488434 | We show that Foxo1 acts as a repressor of Foxa2-dependent (Hnf-3beta-dependent) expression from the Pdx1 promoter. |
| 1204 | 12488434 | We propose that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts. |
| 1205 | 12488434 | The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. |
| 1206 | 12488434 | We report that haploinsufficiency for the forkhead transcription factor Foxo1 reverses beta cell failure in Irs2(-/-) mice through partial restoration of beta cell proliferation and increased expression of the pancreatic transcription factor pancreas/duodenum homeobox gene-1 (Pdx1). |
| 1207 | 12488434 | Foxo1 and Pdx1 exhibit mutually exclusive patterns of nuclear localization in beta cells, and constitutive nuclear expression of a mutant Foxo1 is associated with lack of Pdx1 expression. |
| 1208 | 12488434 | We show that Foxo1 acts as a repressor of Foxa2-dependent (Hnf-3beta-dependent) expression from the Pdx1 promoter. |
| 1209 | 12488434 | We propose that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts. |
| 1210 | 12488434 | The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. |
| 1211 | 12488434 | We report that haploinsufficiency for the forkhead transcription factor Foxo1 reverses beta cell failure in Irs2(-/-) mice through partial restoration of beta cell proliferation and increased expression of the pancreatic transcription factor pancreas/duodenum homeobox gene-1 (Pdx1). |
| 1212 | 12488434 | Foxo1 and Pdx1 exhibit mutually exclusive patterns of nuclear localization in beta cells, and constitutive nuclear expression of a mutant Foxo1 is associated with lack of Pdx1 expression. |
| 1213 | 12488434 | We show that Foxo1 acts as a repressor of Foxa2-dependent (Hnf-3beta-dependent) expression from the Pdx1 promoter. |
| 1214 | 12488434 | We propose that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts. |
| 1215 | 12488434 | The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. |
| 1216 | 12488434 | We report that haploinsufficiency for the forkhead transcription factor Foxo1 reverses beta cell failure in Irs2(-/-) mice through partial restoration of beta cell proliferation and increased expression of the pancreatic transcription factor pancreas/duodenum homeobox gene-1 (Pdx1). |
| 1217 | 12488434 | Foxo1 and Pdx1 exhibit mutually exclusive patterns of nuclear localization in beta cells, and constitutive nuclear expression of a mutant Foxo1 is associated with lack of Pdx1 expression. |
| 1218 | 12488434 | We show that Foxo1 acts as a repressor of Foxa2-dependent (Hnf-3beta-dependent) expression from the Pdx1 promoter. |
| 1219 | 12488434 | We propose that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts. |
| 1220 | 12493745 | Impact of genetic background and ablation of insulin receptor substrate (IRS)-3 on IRS-2 knock-out mice. |
| 1221 | 12493745 | When mice with diabetes were excluded from the analysis of glucose and insulin tolerance test, IRS-2(-/-)IRS-3(-/-) showed a degree of glucose intolerance and insulin resistance similar to those of IRS-2(-/-) mice. |
| 1222 | 12493745 | Both IRS-2(-/-) and IRS-2(-/-)IRS-3(-/-) mice had moderately reduced beta-cell mass despite having insulin resistance. |
| 1223 | 12493745 | Insulin-positive beta-cells were decreased to nearly zero in IRS-2(-/-) mice with diabetes. |
| 1224 | 12493745 | Although Pdx1 and glucose transporter 2 expressions were essentially unaltered in islets from IRS-2(-/-) mice without diabetes, they were dramatically decreased in IRS-2(-/-) mice with diabetes. |
| 1225 | 12498053 | These cells are characterised by the expression of the neural stem cell marker nestin and by their ability to differentiate ex vivo into pancreatic endocrine, exocrine and hepatic phenotypes with the expression of insulin, glucagon, amylase, cytokeratin-19 as well as liver specific proteins such as alpha-fetoprotein. |
| 1226 | 12498053 | The insulinotropic hormone glucagon-like peptide-1 enhances the differentiation of these nestin positive islet derived progenitor (NIP) cells into insulin secreting cells by activation of IDX-1, the key transcription factor for the differentiation into a beta-cell. |
| 1227 | 12503852 | Pancreatic Duodenum Homeobox-1 (PDX-1) is a major regulator of transcription in these cells. |
| 1228 | 12503852 | Glucose, the main physiological regulator of insulin secretion, also regulates insulin gene transcription through PDX-1. |
| 1229 | 12503852 | While acute exposure to high glucose concentrations causes an increase in PDX-1 binding, and consequently in insulin mRNA levels, chronic hyperglycemia (toxic to the beta-cell) leads to a decrease in PDX-1 and insulin levels. |
| 1230 | 12503852 | Pancreatic Duodenum Homeobox-1 (PDX-1) is a major regulator of transcription in these cells. |
| 1231 | 12503852 | Glucose, the main physiological regulator of insulin secretion, also regulates insulin gene transcription through PDX-1. |
| 1232 | 12503852 | While acute exposure to high glucose concentrations causes an increase in PDX-1 binding, and consequently in insulin mRNA levels, chronic hyperglycemia (toxic to the beta-cell) leads to a decrease in PDX-1 and insulin levels. |
| 1233 | 12503852 | Pancreatic Duodenum Homeobox-1 (PDX-1) is a major regulator of transcription in these cells. |
| 1234 | 12503852 | Glucose, the main physiological regulator of insulin secretion, also regulates insulin gene transcription through PDX-1. |
| 1235 | 12503852 | While acute exposure to high glucose concentrations causes an increase in PDX-1 binding, and consequently in insulin mRNA levels, chronic hyperglycemia (toxic to the beta-cell) leads to a decrease in PDX-1 and insulin levels. |
| 1236 | 12525695 | Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells. |
| 1237 | 12525695 | We show that constitutive expression of Pax4 (Pax4(+)), and to a lesser extent Pdx1 (Pdx1(+)), affects the differentiation of ES cells and significantly promote the development of insulin-producing cells. |
| 1238 | 12525695 | In Pax4 overexpressing R1 ES cells, isl-1, ngn3, insulin, islet amyloid polypeptide, and glucose transporter 2 (Glut-2) mRNA levels increase significantly. |
| 1239 | 12525695 | Constitutive Pax4 expression combined with selection of nestin+ cells and histotypic culture conditions give rise to spheroids containing insulin-positive granules typical of embryonal and adult beta cells. |
| 1240 | 12540614 | Expression of betaGK is controlled in beta-cells by cell-enriched (i.e. pancreatic duodenal homeobox 1 [PDX-1]) and ubiquitously (i.e., Pal) distributed factors that bind to and activate from conserved sequence motifs within the upstream promoter region (termed betaGK). |
| 1241 | 12586550 | Pancreatic islets from HD transgenic mice express reduced levels of the pancreatic islet hormones insulin, somatostatin, and glucagon and exhibit intrinsic defects in insulin production. |
| 1242 | 12586550 | HD transgenic mice develop an age-dependent reduction of insulin mRNA expression and diminished expression of key regulators of insulin gene transcription, including the pancreatic homeoprotein PDX-1, E2A proteins, and the coactivators CBP and p300. |
| 1243 | 12586550 | Disrupted expression of a subset of transcription factors in pancreatic beta cells by a polyglutamine expansion tract in the huntingtin protein selectively impairs insulin gene expression to result in insulin deficiency and diabetes. |
| 1244 | 12606496 | The responsible metabolic lesion appears to involve a posttranscriptional defect in pancreas duodenum homeobox-1 (PDX-1) mRNA maturation. |
| 1245 | 12606496 | PDX-1 is a critically important transcription factor for the insulin promoter, is absent in glucotoxic islets, and, when transfected into glucotoxic beta-cells, improves insulin promoter activity. |
| 1246 | 12606496 | The responsible metabolic lesion appears to involve a posttranscriptional defect in pancreas duodenum homeobox-1 (PDX-1) mRNA maturation. |
| 1247 | 12606496 | PDX-1 is a critically important transcription factor for the insulin promoter, is absent in glucotoxic islets, and, when transfected into glucotoxic beta-cells, improves insulin promoter activity. |
| 1248 | 12621453 | Examination of the HUH7-ins cells as well as the parent cell line for beta cell transcription factors showed the presence of NeuroD but not PDX-1. |
| 1249 | 12621453 | PC1 and PC2 were also present in both cell types. |
| 1250 | 12643132 | Maturity-onset diabetes of the young (MODY) are monogenic forms of type 2 diabetes that are characterized by an early disease onset, autosomal-dominant inheritance, and defects in insulin secretion. |
| 1251 | 12643132 | The majority of the MODY subtypes are caused by mutations in transcription factors that include hepatocyte nuclear factor (HNF)-4 alpha, HNF-1 alpha, PDX-1, HNF-1 beta, and NEURO-DI/BETA-2. |
| 1252 | 12643132 | In addition, genetic defects in the glucokinase gene, the glucose sensor of the pancreatic beta cells, and the insulin gene also lead to impaired glucose tolerance. |
| 1253 | 12677187 | Finding a way to increase Pdx-1 expression and the neogenesis of beta cells, perhaps through the stimulating effects of glucagon-like peptide-1, may be useful for the treatment of this crippling disease. |
| 1254 | 12684063 | In this study, we found that the basic helix-loop-helix transcription factor Mad, which usually acts as a repressor to c-Myc, enhances insulin gene transcription. |
| 1255 | 12684063 | In isolated rat islets adenoviral overexpression of Mad augmented insulin mRNA expression and insulin protein content, as well as glucokinase and GLUT2 mRNA expression. |
| 1256 | 12684063 | That the effects of Mad on insulin expression were mediated through PDX-1 was further substantiated by studies showing inhibition of insulin promoter activation by Mad in the presence of mutated PDX-1 binding site. |
| 1257 | 12684063 | Such regulation of insulin expression by Mad with modulation of PDX-1 expression and DNA binding activity could offer useful therapeutic and/or experimental tools to promote insulin production in appropriate cell types. |
| 1258 | 12684063 | In this study, we found that the basic helix-loop-helix transcription factor Mad, which usually acts as a repressor to c-Myc, enhances insulin gene transcription. |
| 1259 | 12684063 | In isolated rat islets adenoviral overexpression of Mad augmented insulin mRNA expression and insulin protein content, as well as glucokinase and GLUT2 mRNA expression. |
| 1260 | 12684063 | That the effects of Mad on insulin expression were mediated through PDX-1 was further substantiated by studies showing inhibition of insulin promoter activation by Mad in the presence of mutated PDX-1 binding site. |
| 1261 | 12684063 | Such regulation of insulin expression by Mad with modulation of PDX-1 expression and DNA binding activity could offer useful therapeutic and/or experimental tools to promote insulin production in appropriate cell types. |
| 1262 | 12688639 | Pancreatic sections were fixed in Bouin's solution and evaluated using immunohistochemistry and image analysis by staining with antibodies for islet hormones: insulin, glucagon; cell proliferation markers: PCNA, BrdU; markers of islet neogenesis: PDX-1, cytokeratin 20; apoptosis was assessed by morphological changes and TUNEL staining. |
| 1263 | 12697734 | Mice with 50% Pdx1, a homeobox gene critical for pancreatic development, had worsening glucose tolerance with age and reduced insulin release in response to glucose, KCl, and arginine from the perfused pancreas. |
| 1264 | 12697734 | Surprisingly, insulin secretion in perifusion or static incubation experiments in response to glucose and other secretagogues was similar in islets isolated from Pdx1(+/-) mice compared with Pdx1(+/+) littermate controls. |
| 1265 | 12697734 | Bcl(XL) and Bcl-2 expression were reduced in Pdx1(+/-) islets. |
| 1266 | 12697734 | These results suggest that an increase in apoptosis, with abnormal regulation of islet number and beta cell mass, represents a key mechanism whereby partial PDX1 deficiency leads to an organ-level defect in insulin secretion and diabetes. |
| 1267 | 12697734 | Mice with 50% Pdx1, a homeobox gene critical for pancreatic development, had worsening glucose tolerance with age and reduced insulin release in response to glucose, KCl, and arginine from the perfused pancreas. |
| 1268 | 12697734 | Surprisingly, insulin secretion in perifusion or static incubation experiments in response to glucose and other secretagogues was similar in islets isolated from Pdx1(+/-) mice compared with Pdx1(+/+) littermate controls. |
| 1269 | 12697734 | Bcl(XL) and Bcl-2 expression were reduced in Pdx1(+/-) islets. |
| 1270 | 12697734 | These results suggest that an increase in apoptosis, with abnormal regulation of islet number and beta cell mass, represents a key mechanism whereby partial PDX1 deficiency leads to an organ-level defect in insulin secretion and diabetes. |
| 1271 | 12697734 | Mice with 50% Pdx1, a homeobox gene critical for pancreatic development, had worsening glucose tolerance with age and reduced insulin release in response to glucose, KCl, and arginine from the perfused pancreas. |
| 1272 | 12697734 | Surprisingly, insulin secretion in perifusion or static incubation experiments in response to glucose and other secretagogues was similar in islets isolated from Pdx1(+/-) mice compared with Pdx1(+/+) littermate controls. |
| 1273 | 12697734 | Bcl(XL) and Bcl-2 expression were reduced in Pdx1(+/-) islets. |
| 1274 | 12697734 | These results suggest that an increase in apoptosis, with abnormal regulation of islet number and beta cell mass, represents a key mechanism whereby partial PDX1 deficiency leads to an organ-level defect in insulin secretion and diabetes. |
| 1275 | 12697734 | Mice with 50% Pdx1, a homeobox gene critical for pancreatic development, had worsening glucose tolerance with age and reduced insulin release in response to glucose, KCl, and arginine from the perfused pancreas. |
| 1276 | 12697734 | Surprisingly, insulin secretion in perifusion or static incubation experiments in response to glucose and other secretagogues was similar in islets isolated from Pdx1(+/-) mice compared with Pdx1(+/+) littermate controls. |
| 1277 | 12697734 | Bcl(XL) and Bcl-2 expression were reduced in Pdx1(+/-) islets. |
| 1278 | 12697734 | These results suggest that an increase in apoptosis, with abnormal regulation of islet number and beta cell mass, represents a key mechanism whereby partial PDX1 deficiency leads to an organ-level defect in insulin secretion and diabetes. |
| 1279 | 12704384 | To explore induced islet neogenesis in the liver as a strategy for the treatment of diabetes, we used helper-dependent adenovirus (HDAD) to deliver the pancreatic duodenal homeobox-1 gene (Ipf1; also known as Pdx-1) to streptozotocin (STZ)-treated diabetic mice. |
| 1280 | 12704384 | The diabetes of STZ mice was partially reversed by HDAD-mediated transfer of NeuroD (Neurod), a factor downstream of Ipf1, and completely reversed by a combination of Neurod and betacellulin (Btc), without producing hepatitis. |
| 1281 | 12704384 | We detected in the liver insulin and other islet-specific transcripts, including proinsulin-processing enzymes, beta-cell-specific glucokinase and sulfonylurea receptor. |
| 1282 | 12704384 | Immunocytochemistry detected the presence of insulin, glucagon, pancreatic polypeptide and somatostatin-producing cells organized into islet clusters; immuno-electron microscopy showed typical insulin-containing granules. |
| 1283 | 12704384 | To explore induced islet neogenesis in the liver as a strategy for the treatment of diabetes, we used helper-dependent adenovirus (HDAD) to deliver the pancreatic duodenal homeobox-1 gene (Ipf1; also known as Pdx-1) to streptozotocin (STZ)-treated diabetic mice. |
| 1284 | 12704384 | The diabetes of STZ mice was partially reversed by HDAD-mediated transfer of NeuroD (Neurod), a factor downstream of Ipf1, and completely reversed by a combination of Neurod and betacellulin (Btc), without producing hepatitis. |
| 1285 | 12704384 | We detected in the liver insulin and other islet-specific transcripts, including proinsulin-processing enzymes, beta-cell-specific glucokinase and sulfonylurea receptor. |
| 1286 | 12704384 | Immunocytochemistry detected the presence of insulin, glucagon, pancreatic polypeptide and somatostatin-producing cells organized into islet clusters; immuno-electron microscopy showed typical insulin-containing granules. |
| 1287 | 12716747 | Recent reports have shown that ES cells can differentiate into insulin-producing cells in response to the transient expression of the pdx-1 gene, after the removal of feeder cells. |
| 1288 | 12716747 | Glucose-responsive insulin-producing cells, derived from our feeder-free ES cells, expressed insulin 2, pdx-1, Pax4, and Isl1 and also the glucagon, somatostatin, and PP genes. |
| 1289 | 12716747 | Recent reports have shown that ES cells can differentiate into insulin-producing cells in response to the transient expression of the pdx-1 gene, after the removal of feeder cells. |
| 1290 | 12716747 | Glucose-responsive insulin-producing cells, derived from our feeder-free ES cells, expressed insulin 2, pdx-1, Pax4, and Isl1 and also the glucagon, somatostatin, and PP genes. |
| 1291 | 12756298 | We explored whether fetal human progenitor liver cells (FH) could be induced to differentiate into insulin-producing cells after expression of the pancreatic duodenal homeobox 1 (Pdx1) gene, which is a key regulator of pancreatic development and insulin expression in beta cells. |
| 1292 | 12756298 | Immortalized FH cells expressing Pdx1 activated multiple beta-cell genes, produced and stored considerable amounts of insulin, and released insulin in a regulated manner in response to glucose. |
| 1293 | 12756298 | We explored whether fetal human progenitor liver cells (FH) could be induced to differentiate into insulin-producing cells after expression of the pancreatic duodenal homeobox 1 (Pdx1) gene, which is a key regulator of pancreatic development and insulin expression in beta cells. |
| 1294 | 12756298 | Immortalized FH cells expressing Pdx1 activated multiple beta-cell genes, produced and stored considerable amounts of insulin, and released insulin in a regulated manner in response to glucose. |
| 1295 | 12829640 | The pancreatic and duodenal homeobox factor-1 (PDX-1), also known as IDX-1/STF-1/IPF1, a homeodomain-containing transcription factor, plays a central role in regulating pancreatic development and insulin gene transcription. |
| 1296 | 12829640 | Furthermore, even in adults, PDX-1 is associated with islet neogenesis and differentiation of insulin-producing cells from progenitor cells. |
| 1297 | 12829640 | Here, we report for the first time that PDX-1 protein can permeate cells due to an Antennapedia-like protein transduction domain sequence in its structure and that transduced PDX-1 functions similarly to endogenous PDX-1; it binds to the insulin promoter and activates its expression. |
| 1298 | 12829640 | PDX-1 protein can also permeate into isolated pancreatic islets, which leads to stimulation of insulin gene expression. |
| 1299 | 12829640 | Moreover, PDX-1 protein transduced into cultures of pancreatic ducts, thought to be islet progenitor cells, induces insulin gene expression. |
| 1300 | 12829640 | These data suggest that PDX-1 protein transduction could be a safe and valuable strategy for enhancing insulin gene transcription and for facilitating differentiation of ductal progenitor cells into insulin-producing cells without requiring gene transfer technology. |
| 1301 | 12829640 | The pancreatic and duodenal homeobox factor-1 (PDX-1), also known as IDX-1/STF-1/IPF1, a homeodomain-containing transcription factor, plays a central role in regulating pancreatic development and insulin gene transcription. |
| 1302 | 12829640 | Furthermore, even in adults, PDX-1 is associated with islet neogenesis and differentiation of insulin-producing cells from progenitor cells. |
| 1303 | 12829640 | Here, we report for the first time that PDX-1 protein can permeate cells due to an Antennapedia-like protein transduction domain sequence in its structure and that transduced PDX-1 functions similarly to endogenous PDX-1; it binds to the insulin promoter and activates its expression. |
| 1304 | 12829640 | PDX-1 protein can also permeate into isolated pancreatic islets, which leads to stimulation of insulin gene expression. |
| 1305 | 12829640 | Moreover, PDX-1 protein transduced into cultures of pancreatic ducts, thought to be islet progenitor cells, induces insulin gene expression. |
| 1306 | 12829640 | These data suggest that PDX-1 protein transduction could be a safe and valuable strategy for enhancing insulin gene transcription and for facilitating differentiation of ductal progenitor cells into insulin-producing cells without requiring gene transfer technology. |
| 1307 | 12829640 | The pancreatic and duodenal homeobox factor-1 (PDX-1), also known as IDX-1/STF-1/IPF1, a homeodomain-containing transcription factor, plays a central role in regulating pancreatic development and insulin gene transcription. |
| 1308 | 12829640 | Furthermore, even in adults, PDX-1 is associated with islet neogenesis and differentiation of insulin-producing cells from progenitor cells. |
| 1309 | 12829640 | Here, we report for the first time that PDX-1 protein can permeate cells due to an Antennapedia-like protein transduction domain sequence in its structure and that transduced PDX-1 functions similarly to endogenous PDX-1; it binds to the insulin promoter and activates its expression. |
| 1310 | 12829640 | PDX-1 protein can also permeate into isolated pancreatic islets, which leads to stimulation of insulin gene expression. |
| 1311 | 12829640 | Moreover, PDX-1 protein transduced into cultures of pancreatic ducts, thought to be islet progenitor cells, induces insulin gene expression. |
| 1312 | 12829640 | These data suggest that PDX-1 protein transduction could be a safe and valuable strategy for enhancing insulin gene transcription and for facilitating differentiation of ductal progenitor cells into insulin-producing cells without requiring gene transfer technology. |
| 1313 | 12829640 | The pancreatic and duodenal homeobox factor-1 (PDX-1), also known as IDX-1/STF-1/IPF1, a homeodomain-containing transcription factor, plays a central role in regulating pancreatic development and insulin gene transcription. |
| 1314 | 12829640 | Furthermore, even in adults, PDX-1 is associated with islet neogenesis and differentiation of insulin-producing cells from progenitor cells. |
| 1315 | 12829640 | Here, we report for the first time that PDX-1 protein can permeate cells due to an Antennapedia-like protein transduction domain sequence in its structure and that transduced PDX-1 functions similarly to endogenous PDX-1; it binds to the insulin promoter and activates its expression. |
| 1316 | 12829640 | PDX-1 protein can also permeate into isolated pancreatic islets, which leads to stimulation of insulin gene expression. |
| 1317 | 12829640 | Moreover, PDX-1 protein transduced into cultures of pancreatic ducts, thought to be islet progenitor cells, induces insulin gene expression. |
| 1318 | 12829640 | These data suggest that PDX-1 protein transduction could be a safe and valuable strategy for enhancing insulin gene transcription and for facilitating differentiation of ductal progenitor cells into insulin-producing cells without requiring gene transfer technology. |
| 1319 | 12829640 | The pancreatic and duodenal homeobox factor-1 (PDX-1), also known as IDX-1/STF-1/IPF1, a homeodomain-containing transcription factor, plays a central role in regulating pancreatic development and insulin gene transcription. |
| 1320 | 12829640 | Furthermore, even in adults, PDX-1 is associated with islet neogenesis and differentiation of insulin-producing cells from progenitor cells. |
| 1321 | 12829640 | Here, we report for the first time that PDX-1 protein can permeate cells due to an Antennapedia-like protein transduction domain sequence in its structure and that transduced PDX-1 functions similarly to endogenous PDX-1; it binds to the insulin promoter and activates its expression. |
| 1322 | 12829640 | PDX-1 protein can also permeate into isolated pancreatic islets, which leads to stimulation of insulin gene expression. |
| 1323 | 12829640 | Moreover, PDX-1 protein transduced into cultures of pancreatic ducts, thought to be islet progenitor cells, induces insulin gene expression. |
| 1324 | 12829640 | These data suggest that PDX-1 protein transduction could be a safe and valuable strategy for enhancing insulin gene transcription and for facilitating differentiation of ductal progenitor cells into insulin-producing cells without requiring gene transfer technology. |
| 1325 | 12829640 | The pancreatic and duodenal homeobox factor-1 (PDX-1), also known as IDX-1/STF-1/IPF1, a homeodomain-containing transcription factor, plays a central role in regulating pancreatic development and insulin gene transcription. |
| 1326 | 12829640 | Furthermore, even in adults, PDX-1 is associated with islet neogenesis and differentiation of insulin-producing cells from progenitor cells. |
| 1327 | 12829640 | Here, we report for the first time that PDX-1 protein can permeate cells due to an Antennapedia-like protein transduction domain sequence in its structure and that transduced PDX-1 functions similarly to endogenous PDX-1; it binds to the insulin promoter and activates its expression. |
| 1328 | 12829640 | PDX-1 protein can also permeate into isolated pancreatic islets, which leads to stimulation of insulin gene expression. |
| 1329 | 12829640 | Moreover, PDX-1 protein transduced into cultures of pancreatic ducts, thought to be islet progenitor cells, induces insulin gene expression. |
| 1330 | 12829640 | These data suggest that PDX-1 protein transduction could be a safe and valuable strategy for enhancing insulin gene transcription and for facilitating differentiation of ductal progenitor cells into insulin-producing cells without requiring gene transfer technology. |
| 1331 | 12829700 | Regulation of Pax4 paired homeodomain gene by neuron-restrictive silencer factor. |
| 1332 | 12829700 | We identified several genes involved in pancreas development that also harbor NRSE-like motifs, including pdx-1, Beta2/NeuroD, and pax4. |
| 1333 | 12829700 | The paired homeodomain transcription factor Pax4 is implicated in the differentiation of the insulin-producing beta-cell lineage because disruption of the pax4 gene results in a severe deficiency of beta-cells and the manifestation of diabetes mellitus in mice. |
| 1334 | 12837760 | Neurogenin3 and hepatic nuclear factor 1 cooperate in activating pancreatic expression of Pax4. |
| 1335 | 12837760 | During fetal development, paired/homeodomain transcription factor Pax4 controls the formation of the insulin-producing beta cells and the somatostatin-producing delta cells in the islets of Langerhans in the pancreas. |
| 1336 | 12837760 | This short sequence contains binding sites for homeodomain transcription factors PDX1 and hepatic nuclear factor (HNF)1, nuclear receptor HNF4alpha, and basic helix-loop-helix factor Neurogenin3. |
| 1337 | 12837760 | In the current study we demonstrate that the HNF1alpha and Neurogenin3 binding sites are critical for activity of the region through synergy between the two proteins. |
| 1338 | 12837760 | Furthermore, exogenous expression of Neurogenin3 is sufficient to induce expression of the endogenous pax4 gene in the mouse pancreatic ductal cell line mPAC, which already expresses HNF1alpha, whereas expression of both Neurogenin3 and HNF1alpha are necessary to activate the pax4 gene in the fibroblast cell line NIH3T3. |
| 1339 | 12837760 | These data demonstrate how Neurogenin3 and HNF1alpha activate the pax4 gene during the cascade of gene expression events that control pancreatic endocrine cell development. |
| 1340 | 12869553 | We have also demonstrated the expression of upstream genes of Pdx-1, such as HNF3beta and HNF1alpha, as well as its downstream genes, including insulin, Glut2, and Nkx6.1, to be well preserved. |
| 1341 | 12882918 | ES cells were evaluated for their ability to differentiate into pancreatic and islet lineage-restricted stages including pancreatic duodenal homeobox 1 (PDX1)-positive pancreatic precursor cells, early endocrine cell progenitors, and islet hormone-producing cells. |
| 1342 | 12882918 | Following growth and differentiation in nonselective medium containing serum, murine ES cells spontaneously differentiated into cells individually expressing each of the four major islet hormones: insulin, glucagon, somatostatin, and pancreatic polypeptide. |
| 1343 | 12882918 | Hormone-positive cells appeared within focal clusters of cells coexpressing PDX1 and the nonclassical hormone markers peptide YY (YY) and islet amyloid polypeptide (IAPP) in combination with the definitive hormones, characteristic of endocrine cells appearing during early pancreaticogenesis. |
| 1344 | 12882918 | ES cells were evaluated for their ability to differentiate into pancreatic and islet lineage-restricted stages including pancreatic duodenal homeobox 1 (PDX1)-positive pancreatic precursor cells, early endocrine cell progenitors, and islet hormone-producing cells. |
| 1345 | 12882918 | Following growth and differentiation in nonselective medium containing serum, murine ES cells spontaneously differentiated into cells individually expressing each of the four major islet hormones: insulin, glucagon, somatostatin, and pancreatic polypeptide. |
| 1346 | 12882918 | Hormone-positive cells appeared within focal clusters of cells coexpressing PDX1 and the nonclassical hormone markers peptide YY (YY) and islet amyloid polypeptide (IAPP) in combination with the definitive hormones, characteristic of endocrine cells appearing during early pancreaticogenesis. |
| 1347 | 12970316 | However, transcriptional activity of both mutant IPF1 proteins, alone or in combination with HNF3 beta/Foxa2, Pbx1, or the heterodimer E47-beta 2 was reduced, findings accounted for by decreased IPF1 steady state levels and not by impaired protein-protein interactions. |
| 1348 | 14509268 | We reproduce this effect of dexamethasone in vitro using organ cultures of mouse embryonic pancreas, and show that it is associated with an elevation of expression of the transcription factor C/EBPbeta (CCAAT/enhancer-binding protein beta) and a reduction of the transcription factor Pdx-1 (pancreatic duodenal homeobox-1). |
| 1349 | 14509268 | We conclude that dexamethasone inhibits insulin expression in pancreatic beta-cells via a mechanism involving down-regulation of Pdx-1 and induction of C/EBPbeta. |
| 1350 | 14509268 | We reproduce this effect of dexamethasone in vitro using organ cultures of mouse embryonic pancreas, and show that it is associated with an elevation of expression of the transcription factor C/EBPbeta (CCAAT/enhancer-binding protein beta) and a reduction of the transcription factor Pdx-1 (pancreatic duodenal homeobox-1). |
| 1351 | 14509268 | We conclude that dexamethasone inhibits insulin expression in pancreatic beta-cells via a mechanism involving down-regulation of Pdx-1 and induction of C/EBPbeta. |
| 1352 | 14602071 | We demonstrate that alpha6beta4 integrin mediates pancreatic epithelial cell adhesion to Netrin-1, whereas recruitment of alpha6beta4 and alpha3beta1 regulate the migration of CK19+/PDX1+ putative pancreatic progenitors on Netrin-1. |
| 1353 | 14633849 | Oxidative stress induces nucleo-cytoplasmic translocation of pancreatic transcription factor PDX-1 through activation of c-Jun NH(2)-terminal kinase. |
| 1354 | 14633849 | Antioxidant treatment of diabetic animals leads to recovery of insulin biosynthesis and increases the expression of its controlling transcription factor, pancreatic duodenal homeobox-1 (PDX-1), in pancreatic beta-cells. |
| 1355 | 14633849 | The addition of a dominant negative form of c-Jun NH(2)-terminal kinase (JNK) inhibited oxidative stress-induced PDX-1 translocation, suggesting an essential role of JNK in mediating this phenomenon. |
| 1356 | 14633849 | The identification of the NES, which overrides the function of the NLS in an oxidative stress-responsive, JNK-dependent manner, supports the complicated regulation of PDX-1 function in vivo and may further the understanding of beta-cell pathophysiology in diabetes. |
| 1357 | 14633849 | Oxidative stress induces nucleo-cytoplasmic translocation of pancreatic transcription factor PDX-1 through activation of c-Jun NH(2)-terminal kinase. |
| 1358 | 14633849 | Antioxidant treatment of diabetic animals leads to recovery of insulin biosynthesis and increases the expression of its controlling transcription factor, pancreatic duodenal homeobox-1 (PDX-1), in pancreatic beta-cells. |
| 1359 | 14633849 | The addition of a dominant negative form of c-Jun NH(2)-terminal kinase (JNK) inhibited oxidative stress-induced PDX-1 translocation, suggesting an essential role of JNK in mediating this phenomenon. |
| 1360 | 14633849 | The identification of the NES, which overrides the function of the NLS in an oxidative stress-responsive, JNK-dependent manner, supports the complicated regulation of PDX-1 function in vivo and may further the understanding of beta-cell pathophysiology in diabetes. |
| 1361 | 14633849 | Oxidative stress induces nucleo-cytoplasmic translocation of pancreatic transcription factor PDX-1 through activation of c-Jun NH(2)-terminal kinase. |
| 1362 | 14633849 | Antioxidant treatment of diabetic animals leads to recovery of insulin biosynthesis and increases the expression of its controlling transcription factor, pancreatic duodenal homeobox-1 (PDX-1), in pancreatic beta-cells. |
| 1363 | 14633849 | The addition of a dominant negative form of c-Jun NH(2)-terminal kinase (JNK) inhibited oxidative stress-induced PDX-1 translocation, suggesting an essential role of JNK in mediating this phenomenon. |
| 1364 | 14633849 | The identification of the NES, which overrides the function of the NLS in an oxidative stress-responsive, JNK-dependent manner, supports the complicated regulation of PDX-1 function in vivo and may further the understanding of beta-cell pathophysiology in diabetes. |
| 1365 | 14633849 | Oxidative stress induces nucleo-cytoplasmic translocation of pancreatic transcription factor PDX-1 through activation of c-Jun NH(2)-terminal kinase. |
| 1366 | 14633849 | Antioxidant treatment of diabetic animals leads to recovery of insulin biosynthesis and increases the expression of its controlling transcription factor, pancreatic duodenal homeobox-1 (PDX-1), in pancreatic beta-cells. |
| 1367 | 14633849 | The addition of a dominant negative form of c-Jun NH(2)-terminal kinase (JNK) inhibited oxidative stress-induced PDX-1 translocation, suggesting an essential role of JNK in mediating this phenomenon. |
| 1368 | 14633849 | The identification of the NES, which overrides the function of the NLS in an oxidative stress-responsive, JNK-dependent manner, supports the complicated regulation of PDX-1 function in vivo and may further the understanding of beta-cell pathophysiology in diabetes. |
| 1369 | 14651921 | In the pancreas, mesenchymal FGF10 is required to maintain the Pdx1-expressing epithelial progenitor cell population, and in the absence of FGF10 signaling, these cells fail to proliferate. |
| 1370 | 14651921 | A hyperplastic pancreas consisting of undifferentiated cells expressing Pdx1, Nkx6.1, and cell adhesion markers normally characterizing early pancreatic progenitor cells resulted. |
| 1371 | 14651921 | The FGF10-positive pancreatic cells expressed Notch1 and Notch2, the Notch-ligand genes Jagged1 and Jagged2, as well as the Notch target gene Hes1. |
| 1372 | 14651921 | In the pancreas, mesenchymal FGF10 is required to maintain the Pdx1-expressing epithelial progenitor cell population, and in the absence of FGF10 signaling, these cells fail to proliferate. |
| 1373 | 14651921 | A hyperplastic pancreas consisting of undifferentiated cells expressing Pdx1, Nkx6.1, and cell adhesion markers normally characterizing early pancreatic progenitor cells resulted. |
| 1374 | 14651921 | The FGF10-positive pancreatic cells expressed Notch1 and Notch2, the Notch-ligand genes Jagged1 and Jagged2, as well as the Notch target gene Hes1. |
| 1375 | 14694850 | Major break-throughs in the genetic sciences of type 2 diabetes have been identifications of insulin receptor gene mutations in syndromes of severe insulin resistance and mutations in pancreatic beta-cell genes in the monogenic sub-group of type 2 diabetes: maturity-onset-diabetes-of-the-young, MODY. |
| 1376 | 14694850 | The studies reported in this thesis are excerpts from an extensive strategy of genetically dissecting (mutation analysis) in: 1) patients with the common form of late-onset type 2 diabetes mellitus the pathways that transduce the insulin signals from the plasma membrane to the activation of glycogen synthesis in skeletal muscle, and in 2) patients with either late-onset type diabetes or MODY the pathways involved in normal beta-cell development and beta-cell function (insulin secretion). |
| 1377 | 14694850 | We could not confirm that a Val985Met variant in the insulin receptor is associated with type 2 diabetes or that the Met326Val of the p85 alpha regulatory subunit of the phosphoinositide-3 kinase is associated with insulin resistance. |
| 1378 | 14694850 | We found no coding mutations (missense) in the insulin signalling protein kinases but we confirmed that the 5 bp deletion (PP1ARE) in the 3'-end of the PPP1R3 gene that encodes the glycogen-associated regulatory subunit of protein phosphatase-1 (PP1G) is associated with insulin resistance estimated as insulin mediated glucose uptake. |
| 1379 | 14694850 | In contrast to protein kinases in skeletal muscles the genes encoding beta-cell transcription factors (IPF-1, NeuroD1/BETA2, and Neurogenin 3) are polymorphic but we could not confirm that the Asp76Asn of IPF-1 is a susceptibility gene for late-onset type 2 diabetes. |
| 1380 | 14694850 | On the other hand we confirmed that the Ala45Thr variant in NeuroD1/BETA2 may represent a susceptibility gene for type 1 diabetes but none of these genes revealed any MODY-specific mutations. |
| 1381 | 14694850 | Also the gene encoding the ATP-regulatable potassium channels of the beta-cell (Kir6.2) is polymorphic but none of these polymorphisms associated with changes in glucose-induced insulin secretion. |
| 1382 | 14729487 | The concerted activities of Pax4 and Nkx2.2 are essential to initiate pancreatic beta-cell differentiation. |
| 1383 | 14729487 | By inactivating the homeobox gene Pax4, we previously demonstrated that its function is required for the formation of mature insulin-producing cells. |
| 1384 | 14729487 | Pax4 activity appears essential for appropriate initiation of beta-cell differentiation because loss of Pax4 prevents the expression of Pdx1, HB9 and insulin in beta-cell precursors. |
| 1385 | 14729487 | This role of Pax4 appears to be accomplished via its genetic interaction with another homeobox gene, Nkx2.2. |
| 1386 | 15001545 | Pancreas duodenum homeobox-1 transcriptional activation requires interactions with p300. |
| 1387 | 15001545 | The homeodomain transcription factor, pancreas duodenum homeobox (PDX)-1, is essential for pancreas development, insulin production, and glucose homeostasis. |
| 1388 | 15001545 | PDX-1 interacts with multiple transcription factors and coregulators, including the coactivator p300, to activate the transcription of the insulin gene and other target genes within pancreatic beta-cells. |
| 1389 | 15001545 | In characterizing the protein-protein interactions of PDX-1 and p300, we identified mutations in PDX-1 that disrupt its function and are associated with increased or decreased interactions with p300. |
| 1390 | 15001545 | Several mutant PDX-1 proteins that are associated with heritable forms of diabetes in humans, in particular the mutant P63fsdelC, exhibited increased binding to a carboxy-terminal segment of p300 in the setting of decreased DNA-binding activities, suggesting that sequestration of p300 by mutant PDX-1 proteins may be an additional mechanism by which insulin gene expression is reduced in heterozygous carriers of pdx-1(ipf-1) mutations. |
| 1391 | 15001545 | The introduction of the point mutations S66A/Y68A in the highly conserved amino-terminal PDX-1 transactivation domain reduced the ability of PDX-1 to interact with p300, substantially diminished the transcriptional activation of PDX-1, and reduced the synergistic activation of glucose-responsive insulin promoter enhancer sequences by PDX-1, E12, and E47. |
| 1392 | 15001545 | We propose that interactions of PDX-1 with p300 are required for the transcriptional activation of PDX-1 target genes. |
| 1393 | 15001545 | Impairment of interactions between PDX-1 and p300 in pancreatic beta-cells may limit insulin production and lead to the development of diabetes. |
| 1394 | 15001545 | Pancreas duodenum homeobox-1 transcriptional activation requires interactions with p300. |
| 1395 | 15001545 | The homeodomain transcription factor, pancreas duodenum homeobox (PDX)-1, is essential for pancreas development, insulin production, and glucose homeostasis. |
| 1396 | 15001545 | PDX-1 interacts with multiple transcription factors and coregulators, including the coactivator p300, to activate the transcription of the insulin gene and other target genes within pancreatic beta-cells. |
| 1397 | 15001545 | In characterizing the protein-protein interactions of PDX-1 and p300, we identified mutations in PDX-1 that disrupt its function and are associated with increased or decreased interactions with p300. |
| 1398 | 15001545 | Several mutant PDX-1 proteins that are associated with heritable forms of diabetes in humans, in particular the mutant P63fsdelC, exhibited increased binding to a carboxy-terminal segment of p300 in the setting of decreased DNA-binding activities, suggesting that sequestration of p300 by mutant PDX-1 proteins may be an additional mechanism by which insulin gene expression is reduced in heterozygous carriers of pdx-1(ipf-1) mutations. |
| 1399 | 15001545 | The introduction of the point mutations S66A/Y68A in the highly conserved amino-terminal PDX-1 transactivation domain reduced the ability of PDX-1 to interact with p300, substantially diminished the transcriptional activation of PDX-1, and reduced the synergistic activation of glucose-responsive insulin promoter enhancer sequences by PDX-1, E12, and E47. |
| 1400 | 15001545 | We propose that interactions of PDX-1 with p300 are required for the transcriptional activation of PDX-1 target genes. |
| 1401 | 15001545 | Impairment of interactions between PDX-1 and p300 in pancreatic beta-cells may limit insulin production and lead to the development of diabetes. |
| 1402 | 15001545 | Pancreas duodenum homeobox-1 transcriptional activation requires interactions with p300. |
| 1403 | 15001545 | The homeodomain transcription factor, pancreas duodenum homeobox (PDX)-1, is essential for pancreas development, insulin production, and glucose homeostasis. |
| 1404 | 15001545 | PDX-1 interacts with multiple transcription factors and coregulators, including the coactivator p300, to activate the transcription of the insulin gene and other target genes within pancreatic beta-cells. |
| 1405 | 15001545 | In characterizing the protein-protein interactions of PDX-1 and p300, we identified mutations in PDX-1 that disrupt its function and are associated with increased or decreased interactions with p300. |
| 1406 | 15001545 | Several mutant PDX-1 proteins that are associated with heritable forms of diabetes in humans, in particular the mutant P63fsdelC, exhibited increased binding to a carboxy-terminal segment of p300 in the setting of decreased DNA-binding activities, suggesting that sequestration of p300 by mutant PDX-1 proteins may be an additional mechanism by which insulin gene expression is reduced in heterozygous carriers of pdx-1(ipf-1) mutations. |
| 1407 | 15001545 | The introduction of the point mutations S66A/Y68A in the highly conserved amino-terminal PDX-1 transactivation domain reduced the ability of PDX-1 to interact with p300, substantially diminished the transcriptional activation of PDX-1, and reduced the synergistic activation of glucose-responsive insulin promoter enhancer sequences by PDX-1, E12, and E47. |
| 1408 | 15001545 | We propose that interactions of PDX-1 with p300 are required for the transcriptional activation of PDX-1 target genes. |
| 1409 | 15001545 | Impairment of interactions between PDX-1 and p300 in pancreatic beta-cells may limit insulin production and lead to the development of diabetes. |
| 1410 | 15001545 | Pancreas duodenum homeobox-1 transcriptional activation requires interactions with p300. |
| 1411 | 15001545 | The homeodomain transcription factor, pancreas duodenum homeobox (PDX)-1, is essential for pancreas development, insulin production, and glucose homeostasis. |
| 1412 | 15001545 | PDX-1 interacts with multiple transcription factors and coregulators, including the coactivator p300, to activate the transcription of the insulin gene and other target genes within pancreatic beta-cells. |
| 1413 | 15001545 | In characterizing the protein-protein interactions of PDX-1 and p300, we identified mutations in PDX-1 that disrupt its function and are associated with increased or decreased interactions with p300. |
| 1414 | 15001545 | Several mutant PDX-1 proteins that are associated with heritable forms of diabetes in humans, in particular the mutant P63fsdelC, exhibited increased binding to a carboxy-terminal segment of p300 in the setting of decreased DNA-binding activities, suggesting that sequestration of p300 by mutant PDX-1 proteins may be an additional mechanism by which insulin gene expression is reduced in heterozygous carriers of pdx-1(ipf-1) mutations. |
| 1415 | 15001545 | The introduction of the point mutations S66A/Y68A in the highly conserved amino-terminal PDX-1 transactivation domain reduced the ability of PDX-1 to interact with p300, substantially diminished the transcriptional activation of PDX-1, and reduced the synergistic activation of glucose-responsive insulin promoter enhancer sequences by PDX-1, E12, and E47. |
| 1416 | 15001545 | We propose that interactions of PDX-1 with p300 are required for the transcriptional activation of PDX-1 target genes. |
| 1417 | 15001545 | Impairment of interactions between PDX-1 and p300 in pancreatic beta-cells may limit insulin production and lead to the development of diabetes. |
| 1418 | 15001545 | Pancreas duodenum homeobox-1 transcriptional activation requires interactions with p300. |
| 1419 | 15001545 | The homeodomain transcription factor, pancreas duodenum homeobox (PDX)-1, is essential for pancreas development, insulin production, and glucose homeostasis. |
| 1420 | 15001545 | PDX-1 interacts with multiple transcription factors and coregulators, including the coactivator p300, to activate the transcription of the insulin gene and other target genes within pancreatic beta-cells. |
| 1421 | 15001545 | In characterizing the protein-protein interactions of PDX-1 and p300, we identified mutations in PDX-1 that disrupt its function and are associated with increased or decreased interactions with p300. |
| 1422 | 15001545 | Several mutant PDX-1 proteins that are associated with heritable forms of diabetes in humans, in particular the mutant P63fsdelC, exhibited increased binding to a carboxy-terminal segment of p300 in the setting of decreased DNA-binding activities, suggesting that sequestration of p300 by mutant PDX-1 proteins may be an additional mechanism by which insulin gene expression is reduced in heterozygous carriers of pdx-1(ipf-1) mutations. |
| 1423 | 15001545 | The introduction of the point mutations S66A/Y68A in the highly conserved amino-terminal PDX-1 transactivation domain reduced the ability of PDX-1 to interact with p300, substantially diminished the transcriptional activation of PDX-1, and reduced the synergistic activation of glucose-responsive insulin promoter enhancer sequences by PDX-1, E12, and E47. |
| 1424 | 15001545 | We propose that interactions of PDX-1 with p300 are required for the transcriptional activation of PDX-1 target genes. |
| 1425 | 15001545 | Impairment of interactions between PDX-1 and p300 in pancreatic beta-cells may limit insulin production and lead to the development of diabetes. |
| 1426 | 15001545 | Pancreas duodenum homeobox-1 transcriptional activation requires interactions with p300. |
| 1427 | 15001545 | The homeodomain transcription factor, pancreas duodenum homeobox (PDX)-1, is essential for pancreas development, insulin production, and glucose homeostasis. |
| 1428 | 15001545 | PDX-1 interacts with multiple transcription factors and coregulators, including the coactivator p300, to activate the transcription of the insulin gene and other target genes within pancreatic beta-cells. |
| 1429 | 15001545 | In characterizing the protein-protein interactions of PDX-1 and p300, we identified mutations in PDX-1 that disrupt its function and are associated with increased or decreased interactions with p300. |
| 1430 | 15001545 | Several mutant PDX-1 proteins that are associated with heritable forms of diabetes in humans, in particular the mutant P63fsdelC, exhibited increased binding to a carboxy-terminal segment of p300 in the setting of decreased DNA-binding activities, suggesting that sequestration of p300 by mutant PDX-1 proteins may be an additional mechanism by which insulin gene expression is reduced in heterozygous carriers of pdx-1(ipf-1) mutations. |
| 1431 | 15001545 | The introduction of the point mutations S66A/Y68A in the highly conserved amino-terminal PDX-1 transactivation domain reduced the ability of PDX-1 to interact with p300, substantially diminished the transcriptional activation of PDX-1, and reduced the synergistic activation of glucose-responsive insulin promoter enhancer sequences by PDX-1, E12, and E47. |
| 1432 | 15001545 | We propose that interactions of PDX-1 with p300 are required for the transcriptional activation of PDX-1 target genes. |
| 1433 | 15001545 | Impairment of interactions between PDX-1 and p300 in pancreatic beta-cells may limit insulin production and lead to the development of diabetes. |
| 1434 | 15001545 | Pancreas duodenum homeobox-1 transcriptional activation requires interactions with p300. |
| 1435 | 15001545 | The homeodomain transcription factor, pancreas duodenum homeobox (PDX)-1, is essential for pancreas development, insulin production, and glucose homeostasis. |
| 1436 | 15001545 | PDX-1 interacts with multiple transcription factors and coregulators, including the coactivator p300, to activate the transcription of the insulin gene and other target genes within pancreatic beta-cells. |
| 1437 | 15001545 | In characterizing the protein-protein interactions of PDX-1 and p300, we identified mutations in PDX-1 that disrupt its function and are associated with increased or decreased interactions with p300. |
| 1438 | 15001545 | Several mutant PDX-1 proteins that are associated with heritable forms of diabetes in humans, in particular the mutant P63fsdelC, exhibited increased binding to a carboxy-terminal segment of p300 in the setting of decreased DNA-binding activities, suggesting that sequestration of p300 by mutant PDX-1 proteins may be an additional mechanism by which insulin gene expression is reduced in heterozygous carriers of pdx-1(ipf-1) mutations. |
| 1439 | 15001545 | The introduction of the point mutations S66A/Y68A in the highly conserved amino-terminal PDX-1 transactivation domain reduced the ability of PDX-1 to interact with p300, substantially diminished the transcriptional activation of PDX-1, and reduced the synergistic activation of glucose-responsive insulin promoter enhancer sequences by PDX-1, E12, and E47. |
| 1440 | 15001545 | We propose that interactions of PDX-1 with p300 are required for the transcriptional activation of PDX-1 target genes. |
| 1441 | 15001545 | Impairment of interactions between PDX-1 and p300 in pancreatic beta-cells may limit insulin production and lead to the development of diabetes. |
| 1442 | 15016234 | To date, five molecular causes of classic MODY have been identified: hepatocyte nuclear factor-4 alpha (HNF-4 alpha; MODY1), glucokinase (MODY2), hepatocyte nuclear factor-1 alpha (HNF-1 alpha; MODY3), insulin promoter factor-1 (IPF-1, MODY4), and hepatocyte nuclear factor-1 beta (HNF-1 beta; MODY5). |
| 1443 | 15028942 | The transcription factor pancreatic duodenal homeobox 1 (PDX-1) is uniformly expressed in early pancreatic buds of embryos as well as the beta and delta cells of the islets of Langerhans. |
| 1444 | 15028942 | It has been shown that PDX-1 is required for maintaining the pancreatic islet functions by activating gene transcriptions including insulin, somatostatin (SST), islet amyloid polypeptide, glucose transporter type 2, and glucokinase. |
| 1445 | 15028942 | The transcription factor pancreatic duodenal homeobox 1 (PDX-1) is uniformly expressed in early pancreatic buds of embryos as well as the beta and delta cells of the islets of Langerhans. |
| 1446 | 15028942 | It has been shown that PDX-1 is required for maintaining the pancreatic islet functions by activating gene transcriptions including insulin, somatostatin (SST), islet amyloid polypeptide, glucose transporter type 2, and glucokinase. |
| 1447 | 15037986 | The role of pdx1 and HNF6 in proliferation and differentiation of endocrine precursors. |
| 1448 | 15037986 | Here, we provide speculation as to the role of pdx1 and HNF6 in these different stages of pancreatic endocrine cell development. |
| 1449 | 15037986 | At the time when islets begin to form within the pancreas, the expression patterns of pdx1 and HNF6 diverge, suggesting distinct functions for each of the genes over the course of endocrine cell development. |
| 1450 | 15037986 | Future studies in this area will rely on conditionally manipulatable systems in combination with lineage-tracing studies for a more accurate assessment of pdx1 and HNF6 function at different stages along the pathway of endocrine cell development. |
| 1451 | 15037986 | The role of pdx1 and HNF6 in proliferation and differentiation of endocrine precursors. |
| 1452 | 15037986 | Here, we provide speculation as to the role of pdx1 and HNF6 in these different stages of pancreatic endocrine cell development. |
| 1453 | 15037986 | At the time when islets begin to form within the pancreas, the expression patterns of pdx1 and HNF6 diverge, suggesting distinct functions for each of the genes over the course of endocrine cell development. |
| 1454 | 15037986 | Future studies in this area will rely on conditionally manipulatable systems in combination with lineage-tracing studies for a more accurate assessment of pdx1 and HNF6 function at different stages along the pathway of endocrine cell development. |
| 1455 | 15037986 | The role of pdx1 and HNF6 in proliferation and differentiation of endocrine precursors. |
| 1456 | 15037986 | Here, we provide speculation as to the role of pdx1 and HNF6 in these different stages of pancreatic endocrine cell development. |
| 1457 | 15037986 | At the time when islets begin to form within the pancreas, the expression patterns of pdx1 and HNF6 diverge, suggesting distinct functions for each of the genes over the course of endocrine cell development. |
| 1458 | 15037986 | Future studies in this area will rely on conditionally manipulatable systems in combination with lineage-tracing studies for a more accurate assessment of pdx1 and HNF6 function at different stages along the pathway of endocrine cell development. |
| 1459 | 15037986 | The role of pdx1 and HNF6 in proliferation and differentiation of endocrine precursors. |
| 1460 | 15037986 | Here, we provide speculation as to the role of pdx1 and HNF6 in these different stages of pancreatic endocrine cell development. |
| 1461 | 15037986 | At the time when islets begin to form within the pancreas, the expression patterns of pdx1 and HNF6 diverge, suggesting distinct functions for each of the genes over the course of endocrine cell development. |
| 1462 | 15037986 | Future studies in this area will rely on conditionally manipulatable systems in combination with lineage-tracing studies for a more accurate assessment of pdx1 and HNF6 function at different stages along the pathway of endocrine cell development. |
| 1463 | 15044356 | GLP-1 receptor activation enhances beta-cell proliferation and promotes islet neogenesis via activation of pdx-1 expression. |
| 1464 | 15044356 | The proliferative effects of GLP-1 appear to involve multiple intracellular pathways, including stimulation of Akt, activation of protein kinase Czeta, and transactivation of the epidermal growth factor receptor through the c-src kinase. |
| 1465 | 15044356 | GLP-1 receptor activation also promotes cell survival in beta-cells and neurons via increased levels of cAMP leading to cAMP response element binding protein activation, enhanced insulin receptor substrate-2 activity and, ultimately, activation of Akt. |
| 1466 | 15047618 | Regulated expression of pdx-1 promotes in vitro differentiation of insulin-producing cells from embryonic stem cells. |
| 1467 | 15047618 | The results showed that pdx-1 expression clearly enhanced the expression of the insulin 2, somatostatin, Kir6.2, glucokinase, neurogenin3, p48, Pax6, PC2, and HNF6 genes in the resulting differentiated cells. |
| 1468 | 15047618 | Thus, exogenous expression of pdx-1 should provide a promising approach for efficiently producing insulin-secreting cells from human ES cells for future therapeutic use in diabetic patients. |
| 1469 | 15047618 | Regulated expression of pdx-1 promotes in vitro differentiation of insulin-producing cells from embryonic stem cells. |
| 1470 | 15047618 | The results showed that pdx-1 expression clearly enhanced the expression of the insulin 2, somatostatin, Kir6.2, glucokinase, neurogenin3, p48, Pax6, PC2, and HNF6 genes in the resulting differentiated cells. |
| 1471 | 15047618 | Thus, exogenous expression of pdx-1 should provide a promising approach for efficiently producing insulin-secreting cells from human ES cells for future therapeutic use in diabetic patients. |
| 1472 | 15047618 | Regulated expression of pdx-1 promotes in vitro differentiation of insulin-producing cells from embryonic stem cells. |
| 1473 | 15047618 | The results showed that pdx-1 expression clearly enhanced the expression of the insulin 2, somatostatin, Kir6.2, glucokinase, neurogenin3, p48, Pax6, PC2, and HNF6 genes in the resulting differentiated cells. |
| 1474 | 15047618 | Thus, exogenous expression of pdx-1 should provide a promising approach for efficiently producing insulin-secreting cells from human ES cells for future therapeutic use in diabetic patients. |
| 1475 | 15110714 | Therefore, we devised the conditional inactivation of Pax6 using the Pdx1 and Pax6 regulatory domains to activate Cre in cells of either the entire pancreatic bud or only in endocrine cell lineages, respectively. |
| 1476 | 15111508 | A significant linkage signal (logarithm of odds [LOD] = 2.98) affecting corrected insulin response to glucose was detected on chromosome 13q between D13787 and D13S252, in the region where the MODY-4 gene has previously been mapped. |
| 1477 | 15111508 | Significant linkage (LOD = 3.09) for insulin response to glucose was found on chromosome 8 between D8S1130 and D8S1106, near the lipoprotein lipase and macrophage scavenger receptor genes. |
| 1478 | 15121856 | Identification of PCIF1, a POZ domain protein that inhibits PDX-1 (MODY4) transcriptional activity. |
| 1479 | 15121856 | Pancreatic-duodenal homeobox 1 (PDX-1) is a Hox-type protein that is a critical requirement for normal pancreas development and for proper differentiation of the endocrine pancreas. |
| 1480 | 15121856 | We have identified a novel POZ domain protein, PDX-1 C terminus-interacting factor 1 (PCIF1)/SPOP, that interacts with PDX-1 both in vitro and in vivo. |
| 1481 | 15121856 | PCIF1 is localized to the nucleus in a speckled pattern, and coexpression of PDX-1 alters the subnuclear distribution of PCIF1. |
| 1482 | 15121856 | Functionally, PCIF1 inhibits PDX-1 transactivation of established target gene promoters in a specific and dose-dependent manner that requires critical amino acids in the PDX-1 C terminus. |
| 1483 | 15121856 | PCIF1 is expressed in adult pancreatic insulin-producing beta cells, and overexpression of PCIF1 inhibits the rat insulin 1 and rat insulin 2 promoters in the MIN6 insulinoma beta cell line. |
| 1484 | 15121856 | The coexpression of PCIF1 with PDX-1 in beta cells and the ability of PCIF1 to repress PDX-1 transactivation suggest that modulation of PDX-1 function by PCIF1 may regulate normal beta cell differentiation. |
| 1485 | 15121856 | Identification of PCIF1, a POZ domain protein that inhibits PDX-1 (MODY4) transcriptional activity. |
| 1486 | 15121856 | Pancreatic-duodenal homeobox 1 (PDX-1) is a Hox-type protein that is a critical requirement for normal pancreas development and for proper differentiation of the endocrine pancreas. |
| 1487 | 15121856 | We have identified a novel POZ domain protein, PDX-1 C terminus-interacting factor 1 (PCIF1)/SPOP, that interacts with PDX-1 both in vitro and in vivo. |
| 1488 | 15121856 | PCIF1 is localized to the nucleus in a speckled pattern, and coexpression of PDX-1 alters the subnuclear distribution of PCIF1. |
| 1489 | 15121856 | Functionally, PCIF1 inhibits PDX-1 transactivation of established target gene promoters in a specific and dose-dependent manner that requires critical amino acids in the PDX-1 C terminus. |
| 1490 | 15121856 | PCIF1 is expressed in adult pancreatic insulin-producing beta cells, and overexpression of PCIF1 inhibits the rat insulin 1 and rat insulin 2 promoters in the MIN6 insulinoma beta cell line. |
| 1491 | 15121856 | The coexpression of PCIF1 with PDX-1 in beta cells and the ability of PCIF1 to repress PDX-1 transactivation suggest that modulation of PDX-1 function by PCIF1 may regulate normal beta cell differentiation. |
| 1492 | 15121856 | Identification of PCIF1, a POZ domain protein that inhibits PDX-1 (MODY4) transcriptional activity. |
| 1493 | 15121856 | Pancreatic-duodenal homeobox 1 (PDX-1) is a Hox-type protein that is a critical requirement for normal pancreas development and for proper differentiation of the endocrine pancreas. |
| 1494 | 15121856 | We have identified a novel POZ domain protein, PDX-1 C terminus-interacting factor 1 (PCIF1)/SPOP, that interacts with PDX-1 both in vitro and in vivo. |
| 1495 | 15121856 | PCIF1 is localized to the nucleus in a speckled pattern, and coexpression of PDX-1 alters the subnuclear distribution of PCIF1. |
| 1496 | 15121856 | Functionally, PCIF1 inhibits PDX-1 transactivation of established target gene promoters in a specific and dose-dependent manner that requires critical amino acids in the PDX-1 C terminus. |
| 1497 | 15121856 | PCIF1 is expressed in adult pancreatic insulin-producing beta cells, and overexpression of PCIF1 inhibits the rat insulin 1 and rat insulin 2 promoters in the MIN6 insulinoma beta cell line. |
| 1498 | 15121856 | The coexpression of PCIF1 with PDX-1 in beta cells and the ability of PCIF1 to repress PDX-1 transactivation suggest that modulation of PDX-1 function by PCIF1 may regulate normal beta cell differentiation. |
| 1499 | 15121856 | Identification of PCIF1, a POZ domain protein that inhibits PDX-1 (MODY4) transcriptional activity. |
| 1500 | 15121856 | Pancreatic-duodenal homeobox 1 (PDX-1) is a Hox-type protein that is a critical requirement for normal pancreas development and for proper differentiation of the endocrine pancreas. |
| 1501 | 15121856 | We have identified a novel POZ domain protein, PDX-1 C terminus-interacting factor 1 (PCIF1)/SPOP, that interacts with PDX-1 both in vitro and in vivo. |
| 1502 | 15121856 | PCIF1 is localized to the nucleus in a speckled pattern, and coexpression of PDX-1 alters the subnuclear distribution of PCIF1. |
| 1503 | 15121856 | Functionally, PCIF1 inhibits PDX-1 transactivation of established target gene promoters in a specific and dose-dependent manner that requires critical amino acids in the PDX-1 C terminus. |
| 1504 | 15121856 | PCIF1 is expressed in adult pancreatic insulin-producing beta cells, and overexpression of PCIF1 inhibits the rat insulin 1 and rat insulin 2 promoters in the MIN6 insulinoma beta cell line. |
| 1505 | 15121856 | The coexpression of PCIF1 with PDX-1 in beta cells and the ability of PCIF1 to repress PDX-1 transactivation suggest that modulation of PDX-1 function by PCIF1 may regulate normal beta cell differentiation. |
| 1506 | 15121856 | Identification of PCIF1, a POZ domain protein that inhibits PDX-1 (MODY4) transcriptional activity. |
| 1507 | 15121856 | Pancreatic-duodenal homeobox 1 (PDX-1) is a Hox-type protein that is a critical requirement for normal pancreas development and for proper differentiation of the endocrine pancreas. |
| 1508 | 15121856 | We have identified a novel POZ domain protein, PDX-1 C terminus-interacting factor 1 (PCIF1)/SPOP, that interacts with PDX-1 both in vitro and in vivo. |
| 1509 | 15121856 | PCIF1 is localized to the nucleus in a speckled pattern, and coexpression of PDX-1 alters the subnuclear distribution of PCIF1. |
| 1510 | 15121856 | Functionally, PCIF1 inhibits PDX-1 transactivation of established target gene promoters in a specific and dose-dependent manner that requires critical amino acids in the PDX-1 C terminus. |
| 1511 | 15121856 | PCIF1 is expressed in adult pancreatic insulin-producing beta cells, and overexpression of PCIF1 inhibits the rat insulin 1 and rat insulin 2 promoters in the MIN6 insulinoma beta cell line. |
| 1512 | 15121856 | The coexpression of PCIF1 with PDX-1 in beta cells and the ability of PCIF1 to repress PDX-1 transactivation suggest that modulation of PDX-1 function by PCIF1 may regulate normal beta cell differentiation. |
| 1513 | 15121856 | Identification of PCIF1, a POZ domain protein that inhibits PDX-1 (MODY4) transcriptional activity. |
| 1514 | 15121856 | Pancreatic-duodenal homeobox 1 (PDX-1) is a Hox-type protein that is a critical requirement for normal pancreas development and for proper differentiation of the endocrine pancreas. |
| 1515 | 15121856 | We have identified a novel POZ domain protein, PDX-1 C terminus-interacting factor 1 (PCIF1)/SPOP, that interacts with PDX-1 both in vitro and in vivo. |
| 1516 | 15121856 | PCIF1 is localized to the nucleus in a speckled pattern, and coexpression of PDX-1 alters the subnuclear distribution of PCIF1. |
| 1517 | 15121856 | Functionally, PCIF1 inhibits PDX-1 transactivation of established target gene promoters in a specific and dose-dependent manner that requires critical amino acids in the PDX-1 C terminus. |
| 1518 | 15121856 | PCIF1 is expressed in adult pancreatic insulin-producing beta cells, and overexpression of PCIF1 inhibits the rat insulin 1 and rat insulin 2 promoters in the MIN6 insulinoma beta cell line. |
| 1519 | 15121856 | The coexpression of PCIF1 with PDX-1 in beta cells and the ability of PCIF1 to repress PDX-1 transactivation suggest that modulation of PDX-1 function by PCIF1 may regulate normal beta cell differentiation. |
| 1520 | 15126294 | As possible mechanism underlying the phenomena, expression of pancreatic and duodenal homeobox factor-1 (also known as IDX-1/STF-1/IPF1), an important transcription factor for the insulin gene, was more clearly visible in the nuclei of islet cells after the antioxidant treatment. |
| 1521 | 15126294 | Under diabetic conditions, JNK is activated by oxidative stress and involved in the suppression of insulin gene expression. |
| 1522 | 15126294 | This JNK effect appears to be mediated in part by nucleocytoplasmic translocation of PDX-1, which is also downstream of JNK activation. |
| 1523 | 15126294 | As possible mechanism underlying the phenomena, expression of pancreatic and duodenal homeobox factor-1 (also known as IDX-1/STF-1/IPF1), an important transcription factor for the insulin gene, was more clearly visible in the nuclei of islet cells after the antioxidant treatment. |
| 1524 | 15126294 | Under diabetic conditions, JNK is activated by oxidative stress and involved in the suppression of insulin gene expression. |
| 1525 | 15126294 | This JNK effect appears to be mediated in part by nucleocytoplasmic translocation of PDX-1, which is also downstream of JNK activation. |
| 1526 | 15142986 | Selective deletion of the Hnf1beta (MODY5) gene in beta-cells leads to altered gene expression and defective insulin release. |
| 1527 | 15142986 | Hepatocyte nuclear factor 1alpha (HNF1alpha) and HNF1beta (or vHNF1) are closely related transcription factors expressed in liver, kidney, gut, and pancreatic beta-cells. |
| 1528 | 15142986 | Human mutations in HNF1alpha or HNF1beta lead to maturity-onset diabetes of the young (MODY3 and MODY5, respectively), and patients present with impaired glucose-stimulated insulin secretion. |
| 1529 | 15142986 | To examine the role of HNF1beta in glucose homeostasis, viable mice deleted for HNF1beta selectively in beta-cells (beta/H1beta-KO mice) were generated using a Cre-LoxP strategy. beta/H1beta-KO mice had normal growth, fertility, fed or fasted plasma glucose and insulin levels, pancreatic insulin content, and insulin sensitivity. |
| 1530 | 15142986 | Moreover, beta/H1beta-KO islets had increased HNF1alpha and Pdx-1, decreased HNF4 mRNA levels, and reduced glucose-stimulated insulin release. |
| 1531 | 15144884 | Pdx-1 enables insulin secretion by regulating synaptotagmin 1 gene expression. |
| 1532 | 15144884 | However, the role of Pdx-1 in the regulation of insulin release is not well established. |
| 1533 | 15144884 | We previously demonstrated that Pdx-1 overcomes the defect in insulin release from the insulin-producing cells derived from small hepatocytes (SHCs). |
| 1534 | 15144884 | In the present study, we identified a new target of Pdx-1 involved in insulin release. |
| 1535 | 15144884 | Pdx-1 positively regulates the transcription of the gene encoding synaptotagmin 1 (Syt1) (a Ca(2+)-sensor that plays a central role in insulin release) through Pdx-1-binding sites within the 3' regulatory region of the Syt1 gene. |
| 1536 | 15144884 | We further demonstrated the essential role of Pdx-1 in insulin secretion by the gene knock-down strategy. |
| 1537 | 15144884 | Small interfering RNA (siRNA) directed against Pdx-1 specifically reduced the levels of Pdx-1 protein and Syt1 transcript in insulinoma lines. |
| 1538 | 15144884 | Our data indicate that Pdx-1 might contribute to the regulation of insulin release by promoting Syt1 expression in vivo, and provide useful information for future therapy of diabetes mellitus. |
| 1539 | 15144884 | Pdx-1 enables insulin secretion by regulating synaptotagmin 1 gene expression. |
| 1540 | 15144884 | However, the role of Pdx-1 in the regulation of insulin release is not well established. |
| 1541 | 15144884 | We previously demonstrated that Pdx-1 overcomes the defect in insulin release from the insulin-producing cells derived from small hepatocytes (SHCs). |
| 1542 | 15144884 | In the present study, we identified a new target of Pdx-1 involved in insulin release. |
| 1543 | 15144884 | Pdx-1 positively regulates the transcription of the gene encoding synaptotagmin 1 (Syt1) (a Ca(2+)-sensor that plays a central role in insulin release) through Pdx-1-binding sites within the 3' regulatory region of the Syt1 gene. |
| 1544 | 15144884 | We further demonstrated the essential role of Pdx-1 in insulin secretion by the gene knock-down strategy. |
| 1545 | 15144884 | Small interfering RNA (siRNA) directed against Pdx-1 specifically reduced the levels of Pdx-1 protein and Syt1 transcript in insulinoma lines. |
| 1546 | 15144884 | Our data indicate that Pdx-1 might contribute to the regulation of insulin release by promoting Syt1 expression in vivo, and provide useful information for future therapy of diabetes mellitus. |
| 1547 | 15144884 | Pdx-1 enables insulin secretion by regulating synaptotagmin 1 gene expression. |
| 1548 | 15144884 | However, the role of Pdx-1 in the regulation of insulin release is not well established. |
| 1549 | 15144884 | We previously demonstrated that Pdx-1 overcomes the defect in insulin release from the insulin-producing cells derived from small hepatocytes (SHCs). |
| 1550 | 15144884 | In the present study, we identified a new target of Pdx-1 involved in insulin release. |
| 1551 | 15144884 | Pdx-1 positively regulates the transcription of the gene encoding synaptotagmin 1 (Syt1) (a Ca(2+)-sensor that plays a central role in insulin release) through Pdx-1-binding sites within the 3' regulatory region of the Syt1 gene. |
| 1552 | 15144884 | We further demonstrated the essential role of Pdx-1 in insulin secretion by the gene knock-down strategy. |
| 1553 | 15144884 | Small interfering RNA (siRNA) directed against Pdx-1 specifically reduced the levels of Pdx-1 protein and Syt1 transcript in insulinoma lines. |
| 1554 | 15144884 | Our data indicate that Pdx-1 might contribute to the regulation of insulin release by promoting Syt1 expression in vivo, and provide useful information for future therapy of diabetes mellitus. |
| 1555 | 15144884 | Pdx-1 enables insulin secretion by regulating synaptotagmin 1 gene expression. |
| 1556 | 15144884 | However, the role of Pdx-1 in the regulation of insulin release is not well established. |
| 1557 | 15144884 | We previously demonstrated that Pdx-1 overcomes the defect in insulin release from the insulin-producing cells derived from small hepatocytes (SHCs). |
| 1558 | 15144884 | In the present study, we identified a new target of Pdx-1 involved in insulin release. |
| 1559 | 15144884 | Pdx-1 positively regulates the transcription of the gene encoding synaptotagmin 1 (Syt1) (a Ca(2+)-sensor that plays a central role in insulin release) through Pdx-1-binding sites within the 3' regulatory region of the Syt1 gene. |
| 1560 | 15144884 | We further demonstrated the essential role of Pdx-1 in insulin secretion by the gene knock-down strategy. |
| 1561 | 15144884 | Small interfering RNA (siRNA) directed against Pdx-1 specifically reduced the levels of Pdx-1 protein and Syt1 transcript in insulinoma lines. |
| 1562 | 15144884 | Our data indicate that Pdx-1 might contribute to the regulation of insulin release by promoting Syt1 expression in vivo, and provide useful information for future therapy of diabetes mellitus. |
| 1563 | 15144884 | Pdx-1 enables insulin secretion by regulating synaptotagmin 1 gene expression. |
| 1564 | 15144884 | However, the role of Pdx-1 in the regulation of insulin release is not well established. |
| 1565 | 15144884 | We previously demonstrated that Pdx-1 overcomes the defect in insulin release from the insulin-producing cells derived from small hepatocytes (SHCs). |
| 1566 | 15144884 | In the present study, we identified a new target of Pdx-1 involved in insulin release. |
| 1567 | 15144884 | Pdx-1 positively regulates the transcription of the gene encoding synaptotagmin 1 (Syt1) (a Ca(2+)-sensor that plays a central role in insulin release) through Pdx-1-binding sites within the 3' regulatory region of the Syt1 gene. |
| 1568 | 15144884 | We further demonstrated the essential role of Pdx-1 in insulin secretion by the gene knock-down strategy. |
| 1569 | 15144884 | Small interfering RNA (siRNA) directed against Pdx-1 specifically reduced the levels of Pdx-1 protein and Syt1 transcript in insulinoma lines. |
| 1570 | 15144884 | Our data indicate that Pdx-1 might contribute to the regulation of insulin release by promoting Syt1 expression in vivo, and provide useful information for future therapy of diabetes mellitus. |
| 1571 | 15144884 | Pdx-1 enables insulin secretion by regulating synaptotagmin 1 gene expression. |
| 1572 | 15144884 | However, the role of Pdx-1 in the regulation of insulin release is not well established. |
| 1573 | 15144884 | We previously demonstrated that Pdx-1 overcomes the defect in insulin release from the insulin-producing cells derived from small hepatocytes (SHCs). |
| 1574 | 15144884 | In the present study, we identified a new target of Pdx-1 involved in insulin release. |
| 1575 | 15144884 | Pdx-1 positively regulates the transcription of the gene encoding synaptotagmin 1 (Syt1) (a Ca(2+)-sensor that plays a central role in insulin release) through Pdx-1-binding sites within the 3' regulatory region of the Syt1 gene. |
| 1576 | 15144884 | We further demonstrated the essential role of Pdx-1 in insulin secretion by the gene knock-down strategy. |
| 1577 | 15144884 | Small interfering RNA (siRNA) directed against Pdx-1 specifically reduced the levels of Pdx-1 protein and Syt1 transcript in insulinoma lines. |
| 1578 | 15144884 | Our data indicate that Pdx-1 might contribute to the regulation of insulin release by promoting Syt1 expression in vivo, and provide useful information for future therapy of diabetes mellitus. |
| 1579 | 15144884 | Pdx-1 enables insulin secretion by regulating synaptotagmin 1 gene expression. |
| 1580 | 15144884 | However, the role of Pdx-1 in the regulation of insulin release is not well established. |
| 1581 | 15144884 | We previously demonstrated that Pdx-1 overcomes the defect in insulin release from the insulin-producing cells derived from small hepatocytes (SHCs). |
| 1582 | 15144884 | In the present study, we identified a new target of Pdx-1 involved in insulin release. |
| 1583 | 15144884 | Pdx-1 positively regulates the transcription of the gene encoding synaptotagmin 1 (Syt1) (a Ca(2+)-sensor that plays a central role in insulin release) through Pdx-1-binding sites within the 3' regulatory region of the Syt1 gene. |
| 1584 | 15144884 | We further demonstrated the essential role of Pdx-1 in insulin secretion by the gene knock-down strategy. |
| 1585 | 15144884 | Small interfering RNA (siRNA) directed against Pdx-1 specifically reduced the levels of Pdx-1 protein and Syt1 transcript in insulinoma lines. |
| 1586 | 15144884 | Our data indicate that Pdx-1 might contribute to the regulation of insulin release by promoting Syt1 expression in vivo, and provide useful information for future therapy of diabetes mellitus. |
| 1587 | 15144884 | Pdx-1 enables insulin secretion by regulating synaptotagmin 1 gene expression. |
| 1588 | 15144884 | However, the role of Pdx-1 in the regulation of insulin release is not well established. |
| 1589 | 15144884 | We previously demonstrated that Pdx-1 overcomes the defect in insulin release from the insulin-producing cells derived from small hepatocytes (SHCs). |
| 1590 | 15144884 | In the present study, we identified a new target of Pdx-1 involved in insulin release. |
| 1591 | 15144884 | Pdx-1 positively regulates the transcription of the gene encoding synaptotagmin 1 (Syt1) (a Ca(2+)-sensor that plays a central role in insulin release) through Pdx-1-binding sites within the 3' regulatory region of the Syt1 gene. |
| 1592 | 15144884 | We further demonstrated the essential role of Pdx-1 in insulin secretion by the gene knock-down strategy. |
| 1593 | 15144884 | Small interfering RNA (siRNA) directed against Pdx-1 specifically reduced the levels of Pdx-1 protein and Syt1 transcript in insulinoma lines. |
| 1594 | 15144884 | Our data indicate that Pdx-1 might contribute to the regulation of insulin release by promoting Syt1 expression in vivo, and provide useful information for future therapy of diabetes mellitus. |
| 1595 | 15144883 | Here we show that SHCs, which are capable of self-renewal and differentiation into hepatocytes, can be induced to generate insulin-producing cells under appropriate culture conditions. |
| 1596 | 15144883 | In addition, enforced expression of the homeodomain transcription factor Pdx1 in these cells contributes to enhancement of insulin release in response to insulin secretagogues. |
| 1597 | 15144883 | These results indicate that the SHCs described here have the ability to differentiate into insulin-producing cells, and further support the idea that engineering to generate insulin-secreting cells could provide a useful resource for future therapies for diabetes mellitus. |
| 1598 | 15151993 | Oligonucleotide microarray analysis reveals PDX1 as an essential regulator of mitochondrial metabolism in rat islets. |
| 1599 | 15151993 | Mutations in the transcription factor IPF1/PDX1 have been associated with type 2 diabetes. |
| 1600 | 15151993 | To elucidate beta-cell dysfunction, PDX1 was suppressed by transduction of rat islets with an adenoviral construct encoding a dominant negative form of PDX1. |
| 1601 | 15151993 | To identify molecular targets implicated in the altered metabolism secretion coupling, DNA microarray analysis was performed on PDX1-deficient and control islets. |
| 1602 | 15151993 | In conclusion, loss of PDX1 function alters expression of mitochondrially encoded genes through regulation of TFAM leading to impaired insulin secretion. |
| 1603 | 15151993 | Oligonucleotide microarray analysis reveals PDX1 as an essential regulator of mitochondrial metabolism in rat islets. |
| 1604 | 15151993 | Mutations in the transcription factor IPF1/PDX1 have been associated with type 2 diabetes. |
| 1605 | 15151993 | To elucidate beta-cell dysfunction, PDX1 was suppressed by transduction of rat islets with an adenoviral construct encoding a dominant negative form of PDX1. |
| 1606 | 15151993 | To identify molecular targets implicated in the altered metabolism secretion coupling, DNA microarray analysis was performed on PDX1-deficient and control islets. |
| 1607 | 15151993 | In conclusion, loss of PDX1 function alters expression of mitochondrially encoded genes through regulation of TFAM leading to impaired insulin secretion. |
| 1608 | 15151993 | Oligonucleotide microarray analysis reveals PDX1 as an essential regulator of mitochondrial metabolism in rat islets. |
| 1609 | 15151993 | Mutations in the transcription factor IPF1/PDX1 have been associated with type 2 diabetes. |
| 1610 | 15151993 | To elucidate beta-cell dysfunction, PDX1 was suppressed by transduction of rat islets with an adenoviral construct encoding a dominant negative form of PDX1. |
| 1611 | 15151993 | To identify molecular targets implicated in the altered metabolism secretion coupling, DNA microarray analysis was performed on PDX1-deficient and control islets. |
| 1612 | 15151993 | In conclusion, loss of PDX1 function alters expression of mitochondrially encoded genes through regulation of TFAM leading to impaired insulin secretion. |
| 1613 | 15151993 | Oligonucleotide microarray analysis reveals PDX1 as an essential regulator of mitochondrial metabolism in rat islets. |
| 1614 | 15151993 | Mutations in the transcription factor IPF1/PDX1 have been associated with type 2 diabetes. |
| 1615 | 15151993 | To elucidate beta-cell dysfunction, PDX1 was suppressed by transduction of rat islets with an adenoviral construct encoding a dominant negative form of PDX1. |
| 1616 | 15151993 | To identify molecular targets implicated in the altered metabolism secretion coupling, DNA microarray analysis was performed on PDX1-deficient and control islets. |
| 1617 | 15151993 | In conclusion, loss of PDX1 function alters expression of mitochondrially encoded genes through regulation of TFAM leading to impaired insulin secretion. |
| 1618 | 15151993 | Oligonucleotide microarray analysis reveals PDX1 as an essential regulator of mitochondrial metabolism in rat islets. |
| 1619 | 15151993 | Mutations in the transcription factor IPF1/PDX1 have been associated with type 2 diabetes. |
| 1620 | 15151993 | To elucidate beta-cell dysfunction, PDX1 was suppressed by transduction of rat islets with an adenoviral construct encoding a dominant negative form of PDX1. |
| 1621 | 15151993 | To identify molecular targets implicated in the altered metabolism secretion coupling, DNA microarray analysis was performed on PDX1-deficient and control islets. |
| 1622 | 15151993 | In conclusion, loss of PDX1 function alters expression of mitochondrially encoded genes through regulation of TFAM leading to impaired insulin secretion. |
| 1623 | 15153417 | These events appear to correlate with pdx-1 gene expression and its ability to bind the insulin gene. |
| 1624 | 15180990 | Differential regulation of islet-specific glucose-6-phosphatase catalytic subunit-related protein gene transcription by Pax-6 and Pdx-1. |
| 1625 | 15180990 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is selectively expressed in islet beta cells and is a major autoantigen in a mouse model of type I diabetes. |
| 1626 | 15180990 | The analysis of IGRP-chloramphenicol acetyltransferase (CAT) fusion gene expression through transient transfection of islet-derived betaTC-3 cells revealed that a promoter region, located between -273 and -254, is essential for high IGRP-CAT fusion gene expression. |
| 1627 | 15180990 | Additional experiments revealed a second non-consensus Pax-6 binding site in the -306/-274 IGRP promoter region. |
| 1628 | 15180990 | Gel retardation assays revealed that another islet-enriched transcription factor, namely Pdx-1, binds four non-consensus elements in the IGRP promoter. |
| 1629 | 15180990 | Although chromatin immunoprecipitation assays show that both Pax-6 and Pdx-1 bind to the IGRP promoter within intact cells, in contrast to the critical role of these factors in beta cell-specific insulin gene expression, IGRP gene transcription appears to require Pax-6 but not Pdx-1. |
| 1630 | 15180990 | Differential regulation of islet-specific glucose-6-phosphatase catalytic subunit-related protein gene transcription by Pax-6 and Pdx-1. |
| 1631 | 15180990 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is selectively expressed in islet beta cells and is a major autoantigen in a mouse model of type I diabetes. |
| 1632 | 15180990 | The analysis of IGRP-chloramphenicol acetyltransferase (CAT) fusion gene expression through transient transfection of islet-derived betaTC-3 cells revealed that a promoter region, located between -273 and -254, is essential for high IGRP-CAT fusion gene expression. |
| 1633 | 15180990 | Additional experiments revealed a second non-consensus Pax-6 binding site in the -306/-274 IGRP promoter region. |
| 1634 | 15180990 | Gel retardation assays revealed that another islet-enriched transcription factor, namely Pdx-1, binds four non-consensus elements in the IGRP promoter. |
| 1635 | 15180990 | Although chromatin immunoprecipitation assays show that both Pax-6 and Pdx-1 bind to the IGRP promoter within intact cells, in contrast to the critical role of these factors in beta cell-specific insulin gene expression, IGRP gene transcription appears to require Pax-6 but not Pdx-1. |
| 1636 | 15180990 | Differential regulation of islet-specific glucose-6-phosphatase catalytic subunit-related protein gene transcription by Pax-6 and Pdx-1. |
| 1637 | 15180990 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is selectively expressed in islet beta cells and is a major autoantigen in a mouse model of type I diabetes. |
| 1638 | 15180990 | The analysis of IGRP-chloramphenicol acetyltransferase (CAT) fusion gene expression through transient transfection of islet-derived betaTC-3 cells revealed that a promoter region, located between -273 and -254, is essential for high IGRP-CAT fusion gene expression. |
| 1639 | 15180990 | Additional experiments revealed a second non-consensus Pax-6 binding site in the -306/-274 IGRP promoter region. |
| 1640 | 15180990 | Gel retardation assays revealed that another islet-enriched transcription factor, namely Pdx-1, binds four non-consensus elements in the IGRP promoter. |
| 1641 | 15180990 | Although chromatin immunoprecipitation assays show that both Pax-6 and Pdx-1 bind to the IGRP promoter within intact cells, in contrast to the critical role of these factors in beta cell-specific insulin gene expression, IGRP gene transcription appears to require Pax-6 but not Pdx-1. |
| 1642 | 15220196 | Specifically, the mBMDS cells expressed multiple genes related to pancreatic beta-cell development and function (insulin I and II, Glut2, glucose kinase, islet amyloid polypeptide, nestin, pancreatic duodenal homeobox-1 [PDX-1], and Pax6). |
| 1643 | 15225136 | Islets formed confluent monolayers when cultured on a type I collagen gel which lacked endocrine phenotypes but were positive for cytokeratin 20 and contained an increased proportion of proliferating c-Kit-expressing cells, with the proportion reaching a maximum of 45+/-6% at 8 weeks of culture. |
| 1644 | 15225136 | Evaluation of transcription factors at the mRNA level revealed constant PDX-1, ngn3 and Pax4 expression, while undifferentiated cell markers, such as Oct4 and alpha-fetoprotein, were also detected frequently after 4 weeks of culture. |
| 1645 | 15281001 | The abnormal glucose-stimulated insulin secretion in MODY1 subjects may be due to reduced glucose transport and glycolysis. |
| 1646 | 15281001 | We recruited a Philippino family with autosomal dominant early-onset type 2 diabetes and screened the proband for mutations in the genes for HNF-1alpha, GCK, HNF-4alpha, IPF-1, HNF-6, and NGN3. |
| 1647 | 15289645 | They start to express CK, the beta-cell transcription factor Pdx1, the neuroendocrine/islet cell markers PGP9.5 and the CCKB receptor for gastrin, and they show pronounced proliferative activity and islet neogenesis. |
| 1648 | 15289647 | Although PDX-1 is critical for promoting beta-cell differentiation, we do not find increased expression of the glucagon-like peptide-1 receptor, a gene that has been reported to be induced by PDX-1. |
| 1649 | 15325843 | Pancreatic islets were isolated to assess insulin and Pdx1 mRNA expression by RT-PCR. |
| 1650 | 15325843 | In addition, insulin and glucagon immunoreactive cells patterns in Langerhans islets were also normal, and normal insulin and Pdx1 mRNA expression patterns were detected during pancreatic recovery in Langerhans islets. |
| 1651 | 15325843 | Pancreatic islets were isolated to assess insulin and Pdx1 mRNA expression by RT-PCR. |
| 1652 | 15325843 | In addition, insulin and glucagon immunoreactive cells patterns in Langerhans islets were also normal, and normal insulin and Pdx1 mRNA expression patterns were detected during pancreatic recovery in Langerhans islets. |
| 1653 | 15331541 | In vitro treatment of embryonic pancreata with dexamethasone, a glucocorticoid agonist, induced a decrease of insulin-expressing cell numbers and a doubling of acinar cell area, indicating that glucocorticoids favored acinar differentiation; in line with this, expression of Pdx-1, Pax-6, and Nkx6.1 was downregulated, whereas the mRNA levels of Ptf1-p48 and Hes-1 were increased. |
| 1654 | 15331541 | The selective inactivation of the GR gene in insulin-expressing beta-cells in mice (using a RIP-Cre transgene) had no measurable consequences on beta- or alpha-cell mass, whereas the absence of GR in the expression domain of Pdx-1 (Pdx-Cre transgene) led to a twofold increased beta-cell mass, with increased islet numbers and size but normal alpha-cell mass in adults. |
| 1655 | 15331541 | In vitro treatment of embryonic pancreata with dexamethasone, a glucocorticoid agonist, induced a decrease of insulin-expressing cell numbers and a doubling of acinar cell area, indicating that glucocorticoids favored acinar differentiation; in line with this, expression of Pdx-1, Pax-6, and Nkx6.1 was downregulated, whereas the mRNA levels of Ptf1-p48 and Hes-1 were increased. |
| 1656 | 15331541 | The selective inactivation of the GR gene in insulin-expressing beta-cells in mice (using a RIP-Cre transgene) had no measurable consequences on beta- or alpha-cell mass, whereas the absence of GR in the expression domain of Pdx-1 (Pdx-Cre transgene) led to a twofold increased beta-cell mass, with increased islet numbers and size but normal alpha-cell mass in adults. |
| 1657 | 15338230 | The other is very similar to hexapeptide NLS sequences identified in pancreatic duodenum homeobox 1 (PDX1). |
| 1658 | 15367898 | A recent developmental study showed that PTF-1a is expressed in almost all parts of pancreatic tissues, in addition to PDX-1, a well-known transcription factor that is essential for pancreas development. |
| 1659 | 15372107 | PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance. |
| 1660 | 15372107 | Here we show that the compensatory islet-growth response to insulin resistance in 2 models--insulin receptor (IR)/IR substrate-1 (IRS-1) double heterozygous mice and liver-specific IR KO (LIRKO) mice--is severely restricted by PDX-1 heterozygosity. |
| 1661 | 15372107 | In both models, superimposition of PDX-1 haploinsufficiency upon the background of insulin resistance completely abrogated the adaptive islet hyperplastic response, and instead the beta cells showed apoptosis resulting in premature death of the mice. |
| 1662 | 15372107 | This study shows that, in postdevelopmental states of beta cell growth, PDX-1 is a critical regulator of beta cell replication and is required for the compensatory response to insulin resistance. |
| 1663 | 15372107 | PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance. |
| 1664 | 15372107 | Here we show that the compensatory islet-growth response to insulin resistance in 2 models--insulin receptor (IR)/IR substrate-1 (IRS-1) double heterozygous mice and liver-specific IR KO (LIRKO) mice--is severely restricted by PDX-1 heterozygosity. |
| 1665 | 15372107 | In both models, superimposition of PDX-1 haploinsufficiency upon the background of insulin resistance completely abrogated the adaptive islet hyperplastic response, and instead the beta cells showed apoptosis resulting in premature death of the mice. |
| 1666 | 15372107 | This study shows that, in postdevelopmental states of beta cell growth, PDX-1 is a critical regulator of beta cell replication and is required for the compensatory response to insulin resistance. |
| 1667 | 15372107 | PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance. |
| 1668 | 15372107 | Here we show that the compensatory islet-growth response to insulin resistance in 2 models--insulin receptor (IR)/IR substrate-1 (IRS-1) double heterozygous mice and liver-specific IR KO (LIRKO) mice--is severely restricted by PDX-1 heterozygosity. |
| 1669 | 15372107 | In both models, superimposition of PDX-1 haploinsufficiency upon the background of insulin resistance completely abrogated the adaptive islet hyperplastic response, and instead the beta cells showed apoptosis resulting in premature death of the mice. |
| 1670 | 15372107 | This study shows that, in postdevelopmental states of beta cell growth, PDX-1 is a critical regulator of beta cell replication and is required for the compensatory response to insulin resistance. |
| 1671 | 15372107 | PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance. |
| 1672 | 15372107 | Here we show that the compensatory islet-growth response to insulin resistance in 2 models--insulin receptor (IR)/IR substrate-1 (IRS-1) double heterozygous mice and liver-specific IR KO (LIRKO) mice--is severely restricted by PDX-1 heterozygosity. |
| 1673 | 15372107 | In both models, superimposition of PDX-1 haploinsufficiency upon the background of insulin resistance completely abrogated the adaptive islet hyperplastic response, and instead the beta cells showed apoptosis resulting in premature death of the mice. |
| 1674 | 15372107 | This study shows that, in postdevelopmental states of beta cell growth, PDX-1 is a critical regulator of beta cell replication and is required for the compensatory response to insulin resistance. |
| 1675 | 15471960 | Immunohistochemical analysis of cells transduced with Ad-pdx-1 demonstrated multiple individual islet or enteroendocrine cells exhibiting both nuclear Pdx-1 and cytoplasmic glucagon-like peptide-1 immunopositivity. |
| 1676 | 15479216 | Moreover, PUFAs prevent insulin resistance by increasing membrane fluidity and GLUT4 transport. |
| 1677 | 15479216 | The depletion of IMTG depots is strictly associated with an improvement of insulin sensitivity, via a reduced acetyl-CoA carboxylase (ACC) mRNA expression and an increased GLUT4 expression and pyruvate dehydrogenase (PDH) activity. |
| 1678 | 15479216 | The decreased insulin gene promoter activity and binding of the pancreas-duodenum homeobox-1 (PDX-1) transcription factor to the insulin gene seem to mediate TG effect in islets. |
| 1679 | 15514704 | As a possible mechanism underlying the phenomena, expression of pancreatic and duodenal homeobox factor-1 (PDX-1), an important transcription factor for the insulin gene, was more clearly visible in the nuclei of islet cells after the antioxidant treatment. |
| 1680 | 15514704 | Furthermore, oxidative stress induces nucleocytoplasmic translocation of PDX-1 through activation of the c-Jun N-terminal kinase (JNK) pathway, which leads to suppression of insulin gene expression. |
| 1681 | 15514704 | As a possible mechanism underlying the phenomena, expression of pancreatic and duodenal homeobox factor-1 (PDX-1), an important transcription factor for the insulin gene, was more clearly visible in the nuclei of islet cells after the antioxidant treatment. |
| 1682 | 15514704 | Furthermore, oxidative stress induces nucleocytoplasmic translocation of PDX-1 through activation of the c-Jun N-terminal kinase (JNK) pathway, which leads to suppression of insulin gene expression. |
| 1683 | 15561912 | Chronic exposure to GLP-1R agonists promotes homologous GLP-1 receptor desensitization in vitro but does not attenuate GLP-1R-dependent glucose homeostasis in vivo. |
| 1684 | 15561912 | Glucagon-like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion and inhibits food intake, gastric emptying, and glucagon secretion, actions that promote reduction of fasting and postprandial glycemia in subjects with type 2 diabetes. |
| 1685 | 15561912 | Similarly, the levels of insulin, pdx-1, and GLP-1 receptor mRNA transcripts were comparable in wild-type and MT-Ex-4 transgenic mice after 1 week of Ex-4 administration. |
| 1686 | 15561943 | The dogma that IGF-I stimulates pancreatic islet growth has been challenged by combinational targeting of IGF or IGF-IR (IGF receptor) genes as well as beta-cell-specific IGF-IR gene deficiency, which caused no defect in islet cell growth. |
| 1687 | 15561943 | To assess the physiological role of locally produced IGF-I, we have developed pancreatic-specific IGF-I gene deficiency (PID) by crossing Pdx1-Cre and IGF-I/loxP mice. |
| 1688 | 15561947 | High glucose is necessary for complete maturation of Pdx1-VP16-expressing hepatic cells into functional insulin-producing cells. |
| 1689 | 15561947 | Pdx1 has been shown to convert hepatocytes into both exocrine and endocrine pancreatic cells in mice, but it fails to selectively convert hepatocytes into pure insulin-producing cells (IPCs). |
| 1690 | 15561947 | We do not however find any expression of the late-stage genes (Pax4, Pax6, Isl-1, and MafA) related to beta-cell development, and the cells do not secrete insulin upon the glucose challenge. |
| 1691 | 15561947 | High glucose is necessary for complete maturation of Pdx1-VP16-expressing hepatic cells into functional insulin-producing cells. |
| 1692 | 15561947 | Pdx1 has been shown to convert hepatocytes into both exocrine and endocrine pancreatic cells in mice, but it fails to selectively convert hepatocytes into pure insulin-producing cells (IPCs). |
| 1693 | 15561947 | We do not however find any expression of the late-stage genes (Pax4, Pax6, Isl-1, and MafA) related to beta-cell development, and the cells do not secrete insulin upon the glucose challenge. |
| 1694 | 15562255 | Reduced PDX-1 expression impairs islet response to insulin resistance and worsens glucose homeostasis. |
| 1695 | 15562255 | Pancreatic duodenal homeodomain-1 (PDX-1), a transcription factor required for normal pancreatic development, also plays a key role in normal insulin secretion by islets. |
| 1696 | 15562255 | To investigate the role of PDX-1 in islet compensation for insulin resistance, we examined glucose disposal, insulin secretion, and islet cell mass in mice of four different genotypes: wild-type mice, mice with one PDX-1 allele inactivated (PDX-1+/-, resulting in impaired insulin secretion), mice with one GLUT4 allele inactivated (GLUT4+/-, resulting in insulin resistance), and mice heterozygous for both PDX-1 and GLUT4 (GLUT4+/-;PDX-1+/-). |
| 1697 | 15562255 | The combination of PDX-1 and GLUT4 heterozygosity markedly prolonged glucose clearance. |
| 1698 | 15562255 | GLUT4+/-;PDX-1+/- mice developed beta-cell hyperplasia but failed to increase their beta-cell insulin content. |
| 1699 | 15562255 | These results indicate that PDX-1 heterozygosity (approximately 60% of normal protein levels) abrogates the beta-cell's compensatory response to insulin resistance, impairs glucose homeostasis, and may contribute to the pathogenesis of type 2 diabetes. |
| 1700 | 15562255 | Reduced PDX-1 expression impairs islet response to insulin resistance and worsens glucose homeostasis. |
| 1701 | 15562255 | Pancreatic duodenal homeodomain-1 (PDX-1), a transcription factor required for normal pancreatic development, also plays a key role in normal insulin secretion by islets. |
| 1702 | 15562255 | To investigate the role of PDX-1 in islet compensation for insulin resistance, we examined glucose disposal, insulin secretion, and islet cell mass in mice of four different genotypes: wild-type mice, mice with one PDX-1 allele inactivated (PDX-1+/-, resulting in impaired insulin secretion), mice with one GLUT4 allele inactivated (GLUT4+/-, resulting in insulin resistance), and mice heterozygous for both PDX-1 and GLUT4 (GLUT4+/-;PDX-1+/-). |
| 1703 | 15562255 | The combination of PDX-1 and GLUT4 heterozygosity markedly prolonged glucose clearance. |
| 1704 | 15562255 | GLUT4+/-;PDX-1+/- mice developed beta-cell hyperplasia but failed to increase their beta-cell insulin content. |
| 1705 | 15562255 | These results indicate that PDX-1 heterozygosity (approximately 60% of normal protein levels) abrogates the beta-cell's compensatory response to insulin resistance, impairs glucose homeostasis, and may contribute to the pathogenesis of type 2 diabetes. |
| 1706 | 15562255 | Reduced PDX-1 expression impairs islet response to insulin resistance and worsens glucose homeostasis. |
| 1707 | 15562255 | Pancreatic duodenal homeodomain-1 (PDX-1), a transcription factor required for normal pancreatic development, also plays a key role in normal insulin secretion by islets. |
| 1708 | 15562255 | To investigate the role of PDX-1 in islet compensation for insulin resistance, we examined glucose disposal, insulin secretion, and islet cell mass in mice of four different genotypes: wild-type mice, mice with one PDX-1 allele inactivated (PDX-1+/-, resulting in impaired insulin secretion), mice with one GLUT4 allele inactivated (GLUT4+/-, resulting in insulin resistance), and mice heterozygous for both PDX-1 and GLUT4 (GLUT4+/-;PDX-1+/-). |
| 1709 | 15562255 | The combination of PDX-1 and GLUT4 heterozygosity markedly prolonged glucose clearance. |
| 1710 | 15562255 | GLUT4+/-;PDX-1+/- mice developed beta-cell hyperplasia but failed to increase their beta-cell insulin content. |
| 1711 | 15562255 | These results indicate that PDX-1 heterozygosity (approximately 60% of normal protein levels) abrogates the beta-cell's compensatory response to insulin resistance, impairs glucose homeostasis, and may contribute to the pathogenesis of type 2 diabetes. |
| 1712 | 15562255 | Reduced PDX-1 expression impairs islet response to insulin resistance and worsens glucose homeostasis. |
| 1713 | 15562255 | Pancreatic duodenal homeodomain-1 (PDX-1), a transcription factor required for normal pancreatic development, also plays a key role in normal insulin secretion by islets. |
| 1714 | 15562255 | To investigate the role of PDX-1 in islet compensation for insulin resistance, we examined glucose disposal, insulin secretion, and islet cell mass in mice of four different genotypes: wild-type mice, mice with one PDX-1 allele inactivated (PDX-1+/-, resulting in impaired insulin secretion), mice with one GLUT4 allele inactivated (GLUT4+/-, resulting in insulin resistance), and mice heterozygous for both PDX-1 and GLUT4 (GLUT4+/-;PDX-1+/-). |
| 1715 | 15562255 | The combination of PDX-1 and GLUT4 heterozygosity markedly prolonged glucose clearance. |
| 1716 | 15562255 | GLUT4+/-;PDX-1+/- mice developed beta-cell hyperplasia but failed to increase their beta-cell insulin content. |
| 1717 | 15562255 | These results indicate that PDX-1 heterozygosity (approximately 60% of normal protein levels) abrogates the beta-cell's compensatory response to insulin resistance, impairs glucose homeostasis, and may contribute to the pathogenesis of type 2 diabetes. |
| 1718 | 15562255 | Reduced PDX-1 expression impairs islet response to insulin resistance and worsens glucose homeostasis. |
| 1719 | 15562255 | Pancreatic duodenal homeodomain-1 (PDX-1), a transcription factor required for normal pancreatic development, also plays a key role in normal insulin secretion by islets. |
| 1720 | 15562255 | To investigate the role of PDX-1 in islet compensation for insulin resistance, we examined glucose disposal, insulin secretion, and islet cell mass in mice of four different genotypes: wild-type mice, mice with one PDX-1 allele inactivated (PDX-1+/-, resulting in impaired insulin secretion), mice with one GLUT4 allele inactivated (GLUT4+/-, resulting in insulin resistance), and mice heterozygous for both PDX-1 and GLUT4 (GLUT4+/-;PDX-1+/-). |
| 1721 | 15562255 | The combination of PDX-1 and GLUT4 heterozygosity markedly prolonged glucose clearance. |
| 1722 | 15562255 | GLUT4+/-;PDX-1+/- mice developed beta-cell hyperplasia but failed to increase their beta-cell insulin content. |
| 1723 | 15562255 | These results indicate that PDX-1 heterozygosity (approximately 60% of normal protein levels) abrogates the beta-cell's compensatory response to insulin resistance, impairs glucose homeostasis, and may contribute to the pathogenesis of type 2 diabetes. |
| 1724 | 15562255 | Reduced PDX-1 expression impairs islet response to insulin resistance and worsens glucose homeostasis. |
| 1725 | 15562255 | Pancreatic duodenal homeodomain-1 (PDX-1), a transcription factor required for normal pancreatic development, also plays a key role in normal insulin secretion by islets. |
| 1726 | 15562255 | To investigate the role of PDX-1 in islet compensation for insulin resistance, we examined glucose disposal, insulin secretion, and islet cell mass in mice of four different genotypes: wild-type mice, mice with one PDX-1 allele inactivated (PDX-1+/-, resulting in impaired insulin secretion), mice with one GLUT4 allele inactivated (GLUT4+/-, resulting in insulin resistance), and mice heterozygous for both PDX-1 and GLUT4 (GLUT4+/-;PDX-1+/-). |
| 1727 | 15562255 | The combination of PDX-1 and GLUT4 heterozygosity markedly prolonged glucose clearance. |
| 1728 | 15562255 | GLUT4+/-;PDX-1+/- mice developed beta-cell hyperplasia but failed to increase their beta-cell insulin content. |
| 1729 | 15562255 | These results indicate that PDX-1 heterozygosity (approximately 60% of normal protein levels) abrogates the beta-cell's compensatory response to insulin resistance, impairs glucose homeostasis, and may contribute to the pathogenesis of type 2 diabetes. |
| 1730 | 15582592 | Constitutively active PDX1 induced efficient insulin production in adult murine liver. |
| 1731 | 15582592 | To generate insulin-producing cells in the liver, recombinant adenovirus containing a constitutively active mutant of PDX1 (PDX1-VP16), designed to activate target genes without the need for protein partners, was prepared and administered intravenously to streptozotocin (STZ)-treated diabetic mice. |
| 1732 | 15582592 | While wt-PDX1 expression exerted small effects on blood glucose levels, treatment with PDX1-VP16 adenovirus efficiently induced insulin production in hepatocytes, resulting in reversal of STZ-induced hyperglycemia. |
| 1733 | 15582592 | On the other hand, albumin and transferrin expressions were observed in insulin-producing cells in the liver, suggesting preservation of hepatocytic functions. |
| 1734 | 15582592 | Thus, transient expression of an active mutant of PDX1 in the liver induced sustained PDX1 and insulin expressions without loss of hepatocytic function. |
| 1735 | 15582592 | Constitutively active PDX1 induced efficient insulin production in adult murine liver. |
| 1736 | 15582592 | To generate insulin-producing cells in the liver, recombinant adenovirus containing a constitutively active mutant of PDX1 (PDX1-VP16), designed to activate target genes without the need for protein partners, was prepared and administered intravenously to streptozotocin (STZ)-treated diabetic mice. |
| 1737 | 15582592 | While wt-PDX1 expression exerted small effects on blood glucose levels, treatment with PDX1-VP16 adenovirus efficiently induced insulin production in hepatocytes, resulting in reversal of STZ-induced hyperglycemia. |
| 1738 | 15582592 | On the other hand, albumin and transferrin expressions were observed in insulin-producing cells in the liver, suggesting preservation of hepatocytic functions. |
| 1739 | 15582592 | Thus, transient expression of an active mutant of PDX1 in the liver induced sustained PDX1 and insulin expressions without loss of hepatocytic function. |
| 1740 | 15582592 | Constitutively active PDX1 induced efficient insulin production in adult murine liver. |
| 1741 | 15582592 | To generate insulin-producing cells in the liver, recombinant adenovirus containing a constitutively active mutant of PDX1 (PDX1-VP16), designed to activate target genes without the need for protein partners, was prepared and administered intravenously to streptozotocin (STZ)-treated diabetic mice. |
| 1742 | 15582592 | While wt-PDX1 expression exerted small effects on blood glucose levels, treatment with PDX1-VP16 adenovirus efficiently induced insulin production in hepatocytes, resulting in reversal of STZ-induced hyperglycemia. |
| 1743 | 15582592 | On the other hand, albumin and transferrin expressions were observed in insulin-producing cells in the liver, suggesting preservation of hepatocytic functions. |
| 1744 | 15582592 | Thus, transient expression of an active mutant of PDX1 in the liver induced sustained PDX1 and insulin expressions without loss of hepatocytic function. |
| 1745 | 15582592 | Constitutively active PDX1 induced efficient insulin production in adult murine liver. |
| 1746 | 15582592 | To generate insulin-producing cells in the liver, recombinant adenovirus containing a constitutively active mutant of PDX1 (PDX1-VP16), designed to activate target genes without the need for protein partners, was prepared and administered intravenously to streptozotocin (STZ)-treated diabetic mice. |
| 1747 | 15582592 | While wt-PDX1 expression exerted small effects on blood glucose levels, treatment with PDX1-VP16 adenovirus efficiently induced insulin production in hepatocytes, resulting in reversal of STZ-induced hyperglycemia. |
| 1748 | 15582592 | On the other hand, albumin and transferrin expressions were observed in insulin-producing cells in the liver, suggesting preservation of hepatocytic functions. |
| 1749 | 15582592 | Thus, transient expression of an active mutant of PDX1 in the liver induced sustained PDX1 and insulin expressions without loss of hepatocytic function. |
| 1750 | 15585742 | RT-PCR analysis showed that Pdx1-positive cells from day 8 cultures expressed the early endoderm markers Ptf1a, Foxa2, Hnf4alpha, Hnf1beta, and Hnf6, consistent with the notion that they corresponded to the early pancreatic endoderm present in the embryonic day 9.5 mouse embryo. |
| 1751 | 15593029 | These genes encode the glycolytic enzyme glucokinase (MODY 2) and the other five encode the transcription factors hepatocyte nuclear factor (HNF) 4alpha (MODY 1), HNF-1alpha (MODY 3), HNF-1beta (MODY 5), insulin promoter factor 1 (IPF-1) (MODY 4) and neurogenic differentiation factor-1 (NeuroD1) (MODY 6). |
| 1752 | 15604203 | Knockout of the genes for Pdx1, Hlxb9, Isl1, or Hex results in an arrest of pancreas development at a very early stage (embryonic d 8-9). |
| 1753 | 15604203 | Hes1 or neurogenin-3, abrogates development of the endocrine pancreas (islets of Langerhans). |
| 1754 | 15604203 | Disruption of transcription factor genes expressed more downstream in the developmental cascade (Beta2/NeuroD, Pax4, NKx2.2, and Nkx6.1) curtails the formation of insulin-producing beta-cells. |
| 1755 | 15605246 | Gene expression profiles during beta cell maturation and after IL-1beta exposure reveal important roles of Pdx-1 and Nkx6.1 for IL-1beta sensitivity. |
| 1756 | 15609091 | Co-localization of nestin and PDX-1 in small evaginations of the main pancreatic duct in adult rats. |
| 1757 | 15622524 | Most of the IL-1beta effects seem to be mediated by NF-kappaB transcription factor activation, but its role in the induction of islet beta-cell apoptosis has not yet been clarified. |
| 1758 | 15622524 | Our results show that TPCK blocked rIL-1beta-mediated early increase of MnSOD activity and beta-cell defence/repair protein expression, suggesting a protective role for NF-kappaB at the beginning of IL-1beta treatment; but, in a second phase, NF-kappaB induces a sustained decrease of specific beta-cell proteins like insulin, GLUT-2 and PDX-1 with a concomitant increase of aspecific proteins and iNOS transcription. |
| 1759 | 15622524 | Since IL-1beta induction of apoptosis is completely prevented by TCPK treatment, this finding underscores the central role of NF-kappaB in this process. |
| 1760 | 15622524 | Thus, our results clearly indicate that NF-kappaB regulates MnSOD genes expression and MnSOD activity, which protects islet beta-cells by IL-1beta damage. |
| 1761 | 15622524 | Furthermore, when the IL-1beta stress impairs islet beta-cell function, NF-kappaB activation regulates the entrance of islet beta-cell into the cell death program. |
| 1762 | 15631623 | The three Fox (forkhead box) group A genes, Foxa1, Foxa2 and Foxa3, are expressed in embryonic endoderm, the germ layer that gives rise to the digestive system, and contribute to the specification of the pancreas and the regulation of glucose homoeostasis. |
| 1763 | 15631623 | Deletion of the Foxa2 gene in pancreatic beta-cells in mice results in a phenotype resembling PHHI (persistent hyperinsulinaemic hypoglycaemia of infancy). |
| 1764 | 15631623 | Molecular analyses have demonstrated that Foxa2 is an important regulator of the genes encoding Sur1, Kir6.2 and Schad (short chain L-3-hydroxyacyl-CoA dehydrogenase), mutation of which causes PHHI in humans. |
| 1765 | 15631623 | An additional winged-helix protein, Foxo1, contributes to pancreatic beta-cell function by regulating the Pdx1 gene, which is required for pancreatic development in cooperation with Foxa2. |
| 1766 | 15652518 | To address the mechanism of beta cell regeneration, mice were treated with streptozotocin (STZ group) or streptozotocin and exendin-4 (STZ + Ex-4 group), and the expression of PDX-1, Ngn3, insulin, IRS-2, and Foxo1 was investigated. |
| 1767 | 15652518 | Exendin-4 upregulated PDX-1 expression which paralleled increased IRS-2 expression and translocation of Foxo1 from nucleus to cytoplasm. |
| 1768 | 15652518 | To address the mechanism of beta cell regeneration, mice were treated with streptozotocin (STZ group) or streptozotocin and exendin-4 (STZ + Ex-4 group), and the expression of PDX-1, Ngn3, insulin, IRS-2, and Foxo1 was investigated. |
| 1769 | 15652518 | Exendin-4 upregulated PDX-1 expression which paralleled increased IRS-2 expression and translocation of Foxo1 from nucleus to cytoplasm. |
| 1770 | 15664997 | MafA, a recently isolated pancreatic beta-cell-specific transcription factor, is a potent activator of insulin gene transcription. |
| 1771 | 15664997 | In this study, we show that MafA overexpression, together with PDX-1 (pancreatic and duodenal homeobox factor-1) and NeuroD, markedly increases insulin gene expression in the liver. |
| 1772 | 15664997 | Furthermore, in streptozotocin-induced diabetic mice, MafA overexpression in the liver, together with PDX-1 and NeuroD, dramatically ameliorated glucose tolerance, while combination of PDX-1 and NeuroD was much less effective. |
| 1773 | 15664997 | MafA, a recently isolated pancreatic beta-cell-specific transcription factor, is a potent activator of insulin gene transcription. |
| 1774 | 15664997 | In this study, we show that MafA overexpression, together with PDX-1 (pancreatic and duodenal homeobox factor-1) and NeuroD, markedly increases insulin gene expression in the liver. |
| 1775 | 15664997 | Furthermore, in streptozotocin-induced diabetic mice, MafA overexpression in the liver, together with PDX-1 and NeuroD, dramatically ameliorated glucose tolerance, while combination of PDX-1 and NeuroD was much less effective. |
| 1776 | 15668393 | At earlier stages, only a dorsal bud rudiment forms transiently and expresses the transcription factors Ipf1 and Hlxb9 but lacks the key transcription factor involved in the acquisition of a pancreatic fate, Ptf1a, as well as all endocrine precursor cells. |
| 1777 | 15668393 | Regional specification of the gut also is perturbed in Tcf2-/- embryos as manifested by ectopic expression of Shh and lack of Ihh and Ipf1 in the posterior stomach and duodenum. |
| 1778 | 15668393 | At earlier stages, only a dorsal bud rudiment forms transiently and expresses the transcription factors Ipf1 and Hlxb9 but lacks the key transcription factor involved in the acquisition of a pancreatic fate, Ptf1a, as well as all endocrine precursor cells. |
| 1779 | 15668393 | Regional specification of the gut also is perturbed in Tcf2-/- embryos as manifested by ectopic expression of Shh and lack of Ihh and Ipf1 in the posterior stomach and duodenum. |
| 1780 | 15671479 | Foxo1, a member of the Fox0 subfamily of winged-helix forkhead transcription factors, is a target of insulin and insulin-like growth factor-1 (IGF-1) signal transduction pathways that activate protein kinase B (PKB) in pancreatic beta cells. |
| 1781 | 15671479 | Foxo1 is a substrate for PKB, and its phosphorylation results in nuclear exclusion with concomitant alterations in gene expression that are important to cellular growth and differentiation. |
| 1782 | 15671479 | Because activation of PKB can require insulin receptor substrate proteins (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase (PI3K), it is of interest to determine whether the activity of Foxo1 is also regulated by heterotrimeric G protein-coupled receptors (GPCRs) with IRS-1 or -2, PI3K, or PKB signaling potential. |
| 1783 | 15671479 | Indeed, studies of beta cells have demonstrated that activation of a GPCR for the blood glucose-lowering hormone GLP-1 leads to major alterations of IRS-2, PI3K, and PKB activity. |
| 1784 | 15671479 | By promoting nuclear exclusion of Foxo1 in a PKB-mediated manner, GLP-1 may up-regulate the expression of a homeodomain transcription factor (PDX-1) that serves as a master regulator of beta-cell growth and differentiation. |
| 1785 | 15677506 | beta-Cell Pdx1 expression is essential for the glucoregulatory, proliferative, and cytoprotective actions of glucagon-like peptide-1. |
| 1786 | 15677506 | We determined the role of the islet beta-cell and the pancreatic duodenal homeobox-1 (Pdx1) transcription factor for GLP-1 receptor (GLP-1R)-dependent actions through analysis of mice with beta-cell-specific inactivation of the Pdx1 gene (beta-cell(Pdx1-/-) mice). |
| 1787 | 15677506 | The GLP-1R agonist exendin-4 (Ex-4) reduced glycemic excursion following intraperitoneal (i.p.) glucose challenge in control littermates (beta-cell(Pdx1+/+) mice) but not in beta-cell(Pdx1-/-) mice. |
| 1788 | 15677506 | Similarly, Ex-4 failed to increase levels of plasma insulin, pancreatic insulin content, and pancreatic insulin mRNA transcripts in beta-cell(Pdx1-/-) mice. |
| 1789 | 15677506 | Moreover, Ex-4 increased the levels of insulin and amylin mRNA transcripts and augmented glucose-stimulated insulin secretion in islets from beta-cell(Pdx1+/+) mice but not in beta-cell(Pdx1-/-) islets. |
| 1790 | 15677506 | beta-Cell Pdx1 expression is essential for the glucoregulatory, proliferative, and cytoprotective actions of glucagon-like peptide-1. |
| 1791 | 15677506 | We determined the role of the islet beta-cell and the pancreatic duodenal homeobox-1 (Pdx1) transcription factor for GLP-1 receptor (GLP-1R)-dependent actions through analysis of mice with beta-cell-specific inactivation of the Pdx1 gene (beta-cell(Pdx1-/-) mice). |
| 1792 | 15677506 | The GLP-1R agonist exendin-4 (Ex-4) reduced glycemic excursion following intraperitoneal (i.p.) glucose challenge in control littermates (beta-cell(Pdx1+/+) mice) but not in beta-cell(Pdx1-/-) mice. |
| 1793 | 15677506 | Similarly, Ex-4 failed to increase levels of plasma insulin, pancreatic insulin content, and pancreatic insulin mRNA transcripts in beta-cell(Pdx1-/-) mice. |
| 1794 | 15677506 | Moreover, Ex-4 increased the levels of insulin and amylin mRNA transcripts and augmented glucose-stimulated insulin secretion in islets from beta-cell(Pdx1+/+) mice but not in beta-cell(Pdx1-/-) islets. |
| 1795 | 15677506 | beta-Cell Pdx1 expression is essential for the glucoregulatory, proliferative, and cytoprotective actions of glucagon-like peptide-1. |
| 1796 | 15677506 | We determined the role of the islet beta-cell and the pancreatic duodenal homeobox-1 (Pdx1) transcription factor for GLP-1 receptor (GLP-1R)-dependent actions through analysis of mice with beta-cell-specific inactivation of the Pdx1 gene (beta-cell(Pdx1-/-) mice). |
| 1797 | 15677506 | The GLP-1R agonist exendin-4 (Ex-4) reduced glycemic excursion following intraperitoneal (i.p.) glucose challenge in control littermates (beta-cell(Pdx1+/+) mice) but not in beta-cell(Pdx1-/-) mice. |
| 1798 | 15677506 | Similarly, Ex-4 failed to increase levels of plasma insulin, pancreatic insulin content, and pancreatic insulin mRNA transcripts in beta-cell(Pdx1-/-) mice. |
| 1799 | 15677506 | Moreover, Ex-4 increased the levels of insulin and amylin mRNA transcripts and augmented glucose-stimulated insulin secretion in islets from beta-cell(Pdx1+/+) mice but not in beta-cell(Pdx1-/-) islets. |
| 1800 | 15677506 | beta-Cell Pdx1 expression is essential for the glucoregulatory, proliferative, and cytoprotective actions of glucagon-like peptide-1. |
| 1801 | 15677506 | We determined the role of the islet beta-cell and the pancreatic duodenal homeobox-1 (Pdx1) transcription factor for GLP-1 receptor (GLP-1R)-dependent actions through analysis of mice with beta-cell-specific inactivation of the Pdx1 gene (beta-cell(Pdx1-/-) mice). |
| 1802 | 15677506 | The GLP-1R agonist exendin-4 (Ex-4) reduced glycemic excursion following intraperitoneal (i.p.) glucose challenge in control littermates (beta-cell(Pdx1+/+) mice) but not in beta-cell(Pdx1-/-) mice. |
| 1803 | 15677506 | Similarly, Ex-4 failed to increase levels of plasma insulin, pancreatic insulin content, and pancreatic insulin mRNA transcripts in beta-cell(Pdx1-/-) mice. |
| 1804 | 15677506 | Moreover, Ex-4 increased the levels of insulin and amylin mRNA transcripts and augmented glucose-stimulated insulin secretion in islets from beta-cell(Pdx1+/+) mice but not in beta-cell(Pdx1-/-) islets. |
| 1805 | 15677506 | beta-Cell Pdx1 expression is essential for the glucoregulatory, proliferative, and cytoprotective actions of glucagon-like peptide-1. |
| 1806 | 15677506 | We determined the role of the islet beta-cell and the pancreatic duodenal homeobox-1 (Pdx1) transcription factor for GLP-1 receptor (GLP-1R)-dependent actions through analysis of mice with beta-cell-specific inactivation of the Pdx1 gene (beta-cell(Pdx1-/-) mice). |
| 1807 | 15677506 | The GLP-1R agonist exendin-4 (Ex-4) reduced glycemic excursion following intraperitoneal (i.p.) glucose challenge in control littermates (beta-cell(Pdx1+/+) mice) but not in beta-cell(Pdx1-/-) mice. |
| 1808 | 15677506 | Similarly, Ex-4 failed to increase levels of plasma insulin, pancreatic insulin content, and pancreatic insulin mRNA transcripts in beta-cell(Pdx1-/-) mice. |
| 1809 | 15677506 | Moreover, Ex-4 increased the levels of insulin and amylin mRNA transcripts and augmented glucose-stimulated insulin secretion in islets from beta-cell(Pdx1+/+) mice but not in beta-cell(Pdx1-/-) islets. |
| 1810 | 15694706 | GLP-1 acts on beta cells, via cAMP-dependent mechanisms, to promote the synthesis and activity of the transcription factor IDX-1, crucial for maintaining the responsiveness of beta cells to an increase in plasma glucose. |
| 1811 | 15694706 | The increased production of GLP-1 associated with frequent coffee consumption could thus be expected to counteract the adverse impact of chronic free fatty acid overexposure on beta cell function in overweight insulin resistant subjects. |
| 1812 | 15734849 | The defects were accompanied by reduced mRNA expression of GLUT1 and -2 and glucokinase and by diminished glucose oxidation. |
| 1813 | 15734849 | Furthermore, the expression of insulin was decreased, and that of pancreatic duodenal homeobox-1 (PDX-1) and forkhead box O1 (Foxo-1) was increased. |
| 1814 | 15743769 | Mechanism of insulin gene regulation by the pancreatic transcription factor Pdx-1: application of pre-mRNA analysis and chromatin immunoprecipitation to assess formation of functional transcriptional complexes. |
| 1815 | 15743769 | To determine the mechanism underlying regulation of the insulin gene by Pdx-1, we performed a kinetic analysis of insulin transcription following adenovirus-mediated delivery of a small interfering RNA specific for pdx-1 into insulinoma cells and pancreatic islets to diminish endogenous Pdx-1 protein. insulin transcription was assessed by measuring both a long half-life insulin mRNA (mature mRNA) and a short half-life insulin pre-mRNA species by real-time reverse transcriptase-PCR. |
| 1816 | 15743769 | In contrast, mature mRNA levels showed strikingly smaller and delayed declines, suggesting that the longer half-life of this species underestimates the contribution of Pdx-1 to insulin transcription. |
| 1817 | 15743769 | Chromatin immunoprecipitation assays revealed that the decrease in insulin transcription was associated with decreases in the occupancies of Pdx-1 and p300 at the proximal insulin promoter. |
| 1818 | 15743769 | Our results suggest that Pdx-1 directly regulates insulin transcription through formation of a complex with transcriptional coactivators on the proximal insulin promoter. |
| 1819 | 15743769 | Mechanism of insulin gene regulation by the pancreatic transcription factor Pdx-1: application of pre-mRNA analysis and chromatin immunoprecipitation to assess formation of functional transcriptional complexes. |
| 1820 | 15743769 | To determine the mechanism underlying regulation of the insulin gene by Pdx-1, we performed a kinetic analysis of insulin transcription following adenovirus-mediated delivery of a small interfering RNA specific for pdx-1 into insulinoma cells and pancreatic islets to diminish endogenous Pdx-1 protein. insulin transcription was assessed by measuring both a long half-life insulin mRNA (mature mRNA) and a short half-life insulin pre-mRNA species by real-time reverse transcriptase-PCR. |
| 1821 | 15743769 | In contrast, mature mRNA levels showed strikingly smaller and delayed declines, suggesting that the longer half-life of this species underestimates the contribution of Pdx-1 to insulin transcription. |
| 1822 | 15743769 | Chromatin immunoprecipitation assays revealed that the decrease in insulin transcription was associated with decreases in the occupancies of Pdx-1 and p300 at the proximal insulin promoter. |
| 1823 | 15743769 | Our results suggest that Pdx-1 directly regulates insulin transcription through formation of a complex with transcriptional coactivators on the proximal insulin promoter. |
| 1824 | 15743769 | Mechanism of insulin gene regulation by the pancreatic transcription factor Pdx-1: application of pre-mRNA analysis and chromatin immunoprecipitation to assess formation of functional transcriptional complexes. |
| 1825 | 15743769 | To determine the mechanism underlying regulation of the insulin gene by Pdx-1, we performed a kinetic analysis of insulin transcription following adenovirus-mediated delivery of a small interfering RNA specific for pdx-1 into insulinoma cells and pancreatic islets to diminish endogenous Pdx-1 protein. insulin transcription was assessed by measuring both a long half-life insulin mRNA (mature mRNA) and a short half-life insulin pre-mRNA species by real-time reverse transcriptase-PCR. |
| 1826 | 15743769 | In contrast, mature mRNA levels showed strikingly smaller and delayed declines, suggesting that the longer half-life of this species underestimates the contribution of Pdx-1 to insulin transcription. |
| 1827 | 15743769 | Chromatin immunoprecipitation assays revealed that the decrease in insulin transcription was associated with decreases in the occupancies of Pdx-1 and p300 at the proximal insulin promoter. |
| 1828 | 15743769 | Our results suggest that Pdx-1 directly regulates insulin transcription through formation of a complex with transcriptional coactivators on the proximal insulin promoter. |
| 1829 | 15743769 | Mechanism of insulin gene regulation by the pancreatic transcription factor Pdx-1: application of pre-mRNA analysis and chromatin immunoprecipitation to assess formation of functional transcriptional complexes. |
| 1830 | 15743769 | To determine the mechanism underlying regulation of the insulin gene by Pdx-1, we performed a kinetic analysis of insulin transcription following adenovirus-mediated delivery of a small interfering RNA specific for pdx-1 into insulinoma cells and pancreatic islets to diminish endogenous Pdx-1 protein. insulin transcription was assessed by measuring both a long half-life insulin mRNA (mature mRNA) and a short half-life insulin pre-mRNA species by real-time reverse transcriptase-PCR. |
| 1831 | 15743769 | In contrast, mature mRNA levels showed strikingly smaller and delayed declines, suggesting that the longer half-life of this species underestimates the contribution of Pdx-1 to insulin transcription. |
| 1832 | 15743769 | Chromatin immunoprecipitation assays revealed that the decrease in insulin transcription was associated with decreases in the occupancies of Pdx-1 and p300 at the proximal insulin promoter. |
| 1833 | 15743769 | Our results suggest that Pdx-1 directly regulates insulin transcription through formation of a complex with transcriptional coactivators on the proximal insulin promoter. |
| 1834 | 15743769 | Mechanism of insulin gene regulation by the pancreatic transcription factor Pdx-1: application of pre-mRNA analysis and chromatin immunoprecipitation to assess formation of functional transcriptional complexes. |
| 1835 | 15743769 | To determine the mechanism underlying regulation of the insulin gene by Pdx-1, we performed a kinetic analysis of insulin transcription following adenovirus-mediated delivery of a small interfering RNA specific for pdx-1 into insulinoma cells and pancreatic islets to diminish endogenous Pdx-1 protein. insulin transcription was assessed by measuring both a long half-life insulin mRNA (mature mRNA) and a short half-life insulin pre-mRNA species by real-time reverse transcriptase-PCR. |
| 1836 | 15743769 | In contrast, mature mRNA levels showed strikingly smaller and delayed declines, suggesting that the longer half-life of this species underestimates the contribution of Pdx-1 to insulin transcription. |
| 1837 | 15743769 | Chromatin immunoprecipitation assays revealed that the decrease in insulin transcription was associated with decreases in the occupancies of Pdx-1 and p300 at the proximal insulin promoter. |
| 1838 | 15743769 | Our results suggest that Pdx-1 directly regulates insulin transcription through formation of a complex with transcriptional coactivators on the proximal insulin promoter. |
| 1839 | 15754742 | In addition to MODY, IPF-1 mutations are suggested to predispose to common late-onset T2DM with different penetration of the mutations reflected in their in vitro activity. |
| 1840 | 15756539 | Suppression of Pdx-1 perturbs proinsulin processing, insulin secretion and GLP-1 signalling in INS-1 cells. |
| 1841 | 15765120 | TC islets contained cells stained positive for insulin, glucagon, somatostatin, pancreatic polypeptide, as well as PDX-1, chromogranin, and hepatocyte-derived growth factor receptor, c-met. |
| 1842 | 15765120 | Duct-like cells in TC of BBdp rats expressed markers of committed endocrine precursors: PDX-1, neurogenin 3 and protein gene product 9.5. |
| 1843 | 15765120 | TC islets contained cells stained positive for insulin, glucagon, somatostatin, pancreatic polypeptide, as well as PDX-1, chromogranin, and hepatocyte-derived growth factor receptor, c-met. |
| 1844 | 15765120 | Duct-like cells in TC of BBdp rats expressed markers of committed endocrine precursors: PDX-1, neurogenin 3 and protein gene product 9.5. |
| 1845 | 15793239 | PDX-1/VP16 fusion protein, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance. |
| 1846 | 15793239 | In this study, we showed that a modified form of the pancreatic and duodenal homeobox factor 1 (PDX-1) carrying the VP16 transcriptional activation domain (PDX-1/VP16) markedly increases insulin biosynthesis and induces various pancreas-related factors in the liver, especially in the presence of NeuroD or neurogenin 3 (Ngn3). |
| 1847 | 15793239 | Furthermore, in streptozotocin-induced diabetic mice, PDX-1/VP16 overexpression, together with NeuroD or Ngn3, drastically ameliorated glucose tolerance. |
| 1848 | 15793239 | Thus PDX-1/VP16 expression, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance. |
| 1849 | 15793239 | PDX-1/VP16 fusion protein, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance. |
| 1850 | 15793239 | In this study, we showed that a modified form of the pancreatic and duodenal homeobox factor 1 (PDX-1) carrying the VP16 transcriptional activation domain (PDX-1/VP16) markedly increases insulin biosynthesis and induces various pancreas-related factors in the liver, especially in the presence of NeuroD or neurogenin 3 (Ngn3). |
| 1851 | 15793239 | Furthermore, in streptozotocin-induced diabetic mice, PDX-1/VP16 overexpression, together with NeuroD or Ngn3, drastically ameliorated glucose tolerance. |
| 1852 | 15793239 | Thus PDX-1/VP16 expression, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance. |
| 1853 | 15793239 | PDX-1/VP16 fusion protein, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance. |
| 1854 | 15793239 | In this study, we showed that a modified form of the pancreatic and duodenal homeobox factor 1 (PDX-1) carrying the VP16 transcriptional activation domain (PDX-1/VP16) markedly increases insulin biosynthesis and induces various pancreas-related factors in the liver, especially in the presence of NeuroD or neurogenin 3 (Ngn3). |
| 1855 | 15793239 | Furthermore, in streptozotocin-induced diabetic mice, PDX-1/VP16 overexpression, together with NeuroD or Ngn3, drastically ameliorated glucose tolerance. |
| 1856 | 15793239 | Thus PDX-1/VP16 expression, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance. |
| 1857 | 15793239 | PDX-1/VP16 fusion protein, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance. |
| 1858 | 15793239 | In this study, we showed that a modified form of the pancreatic and duodenal homeobox factor 1 (PDX-1) carrying the VP16 transcriptional activation domain (PDX-1/VP16) markedly increases insulin biosynthesis and induces various pancreas-related factors in the liver, especially in the presence of NeuroD or neurogenin 3 (Ngn3). |
| 1859 | 15793239 | Furthermore, in streptozotocin-induced diabetic mice, PDX-1/VP16 overexpression, together with NeuroD or Ngn3, drastically ameliorated glucose tolerance. |
| 1860 | 15793239 | Thus PDX-1/VP16 expression, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance. |
| 1861 | 15896300 | PDX-1 plays a central role in differentiation of insulin-producing cells. |
| 1862 | 15896300 | We previously reported that exogenous PDX-1 protein can permeate cells and induce insulin gene expression in progenitor cells. |
| 1863 | 15896300 | These data suggest that mechanism of transduction of PDX-1 protein is by endocytosis and subsequent release from the endosome homogeneously in cytoplasm and nuclei, and that PDX-1 protein transduction could be a valuable strategy for facilitating differentiation of progenitor cells into insulin-producing cells. |
| 1864 | 15896300 | PDX-1 plays a central role in differentiation of insulin-producing cells. |
| 1865 | 15896300 | We previously reported that exogenous PDX-1 protein can permeate cells and induce insulin gene expression in progenitor cells. |
| 1866 | 15896300 | These data suggest that mechanism of transduction of PDX-1 protein is by endocytosis and subsequent release from the endosome homogeneously in cytoplasm and nuclei, and that PDX-1 protein transduction could be a valuable strategy for facilitating differentiation of progenitor cells into insulin-producing cells. |
| 1867 | 15896300 | PDX-1 plays a central role in differentiation of insulin-producing cells. |
| 1868 | 15896300 | We previously reported that exogenous PDX-1 protein can permeate cells and induce insulin gene expression in progenitor cells. |
| 1869 | 15896300 | These data suggest that mechanism of transduction of PDX-1 protein is by endocytosis and subsequent release from the endosome homogeneously in cytoplasm and nuclei, and that PDX-1 protein transduction could be a valuable strategy for facilitating differentiation of progenitor cells into insulin-producing cells. |
| 1870 | 15899968 | By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. |
| 1871 | 15899968 | PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. |
| 1872 | 15899968 | By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. |
| 1873 | 15899968 | PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. |
| 1874 | 15923615 | MafA is a key regulator of glucose-stimulated insulin secretion. |
| 1875 | 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. |
| 1876 | 15923615 | To analyze the role of MafA in insulin transcription and glucose homeostasis in vivo, we generated MafA-deficient mice. |
| 1877 | 15923615 | Further analysis revealed that insulin 1, insulin 2, Pdx1, Beta2, and Glut-2 transcripts are diminished in MafA-deficient mice. |
| 1878 | 15923615 | These results show that MafA is a key regulator of glucose-stimulated insulin secretion in vivo. |
| 1879 | 15928194 | The cell lineage obtained expressed Pdx1, Pax6, Isl1, AChE, MBP, TH, and GS genes, confirming ectodermal commitment, even though some of these factors are also expressed in endoderm. |
| 1880 | 15928194 | Co-expression of insulin II and nestin was observed in monolayer culture and in the presence of specific conditioned media. |
| 1881 | 15935394 | The release of insulin, the expression of preproinsulin (PPI), glucose transporter2 (GLUT2) and pancreatic duodenal homeobox-1 (PDX-1), and levels of intracellular free Ca++([Ca++]i) were measured in rat pancreatic islets treated with or without high concentrations of FFA (0.1 and 1.0 mM oleic acid) for 24 h. |
| 1882 | 15935394 | Elevated expression of PPI, PDX-1 and GLUT2 was also observed after treatment of the islets with oleic acid, which may partially contribute to the increased basal insulin secretion. |
| 1883 | 15935394 | The release of insulin, the expression of preproinsulin (PPI), glucose transporter2 (GLUT2) and pancreatic duodenal homeobox-1 (PDX-1), and levels of intracellular free Ca++([Ca++]i) were measured in rat pancreatic islets treated with or without high concentrations of FFA (0.1 and 1.0 mM oleic acid) for 24 h. |
| 1884 | 15935394 | Elevated expression of PPI, PDX-1 and GLUT2 was also observed after treatment of the islets with oleic acid, which may partially contribute to the increased basal insulin secretion. |
| 1885 | 15944145 | Palmitate inhibits insulin gene expression by altering PDX-1 nuclear localization and reducing MafA expression in isolated rat islets of Langerhans. |
| 1886 | 15944145 | This study was designed to assess whether palmitate alters the expression and binding activity of the key regulatory factors pancreas-duodenum homeobox-1 (PDX-1), MafA, and Beta2, which respectively bind to the A3, C1, and E1 elements in the proximal region of the insulin promoter. |
| 1887 | 15944145 | Combined adenovirus-mediated overexpression of PDX-1 and MafA in islets completely prevented the inhibition of insulin gene expression by palmitate. |
| 1888 | 15944145 | These results demonstrate that prolonged exposure of islets to palmitate inhibits insulin gene transcription by impairing nuclear localization of PDX-1 and cellular expression of MafA. |
| 1889 | 15944145 | Palmitate inhibits insulin gene expression by altering PDX-1 nuclear localization and reducing MafA expression in isolated rat islets of Langerhans. |
| 1890 | 15944145 | This study was designed to assess whether palmitate alters the expression and binding activity of the key regulatory factors pancreas-duodenum homeobox-1 (PDX-1), MafA, and Beta2, which respectively bind to the A3, C1, and E1 elements in the proximal region of the insulin promoter. |
| 1891 | 15944145 | Combined adenovirus-mediated overexpression of PDX-1 and MafA in islets completely prevented the inhibition of insulin gene expression by palmitate. |
| 1892 | 15944145 | These results demonstrate that prolonged exposure of islets to palmitate inhibits insulin gene transcription by impairing nuclear localization of PDX-1 and cellular expression of MafA. |
| 1893 | 15944145 | Palmitate inhibits insulin gene expression by altering PDX-1 nuclear localization and reducing MafA expression in isolated rat islets of Langerhans. |
| 1894 | 15944145 | This study was designed to assess whether palmitate alters the expression and binding activity of the key regulatory factors pancreas-duodenum homeobox-1 (PDX-1), MafA, and Beta2, which respectively bind to the A3, C1, and E1 elements in the proximal region of the insulin promoter. |
| 1895 | 15944145 | Combined adenovirus-mediated overexpression of PDX-1 and MafA in islets completely prevented the inhibition of insulin gene expression by palmitate. |
| 1896 | 15944145 | These results demonstrate that prolonged exposure of islets to palmitate inhibits insulin gene transcription by impairing nuclear localization of PDX-1 and cellular expression of MafA. |
| 1897 | 15944145 | Palmitate inhibits insulin gene expression by altering PDX-1 nuclear localization and reducing MafA expression in isolated rat islets of Langerhans. |
| 1898 | 15944145 | This study was designed to assess whether palmitate alters the expression and binding activity of the key regulatory factors pancreas-duodenum homeobox-1 (PDX-1), MafA, and Beta2, which respectively bind to the A3, C1, and E1 elements in the proximal region of the insulin promoter. |
| 1899 | 15944145 | Combined adenovirus-mediated overexpression of PDX-1 and MafA in islets completely prevented the inhibition of insulin gene expression by palmitate. |
| 1900 | 15944145 | These results demonstrate that prolonged exposure of islets to palmitate inhibits insulin gene transcription by impairing nuclear localization of PDX-1 and cellular expression of MafA. |
| 1901 | 15955369 | The majority of proteins associated with MODY are transcription factors, such as hepatocyte nuclear factor 4alpha (HNF-4alpha), HNF-1alpha, insulin promoter factor-1 (IPF-1), HNF-1beta, and NEUROD1. |
| 1902 | 15955369 | In addition, some evidence exists that genes, such as adiponectin, IRS-1, and some others may also influence the susceptibility to T2DM. |
| 1903 | 15979049 | When comparing gene expression, by quantitative real-time RT-PCR, in pancreatic exocrine tissue from obese non-diabetic subjects with increased islet mass, we found that Pbx-1 and Pdx-1 were up-regulated (5.9+/-1.2 and 2.4+/-0.6 versus non-obese). |
| 1904 | 15979049 | Immunohistochemistry confirmed PBX-1 over-expression and its cytoplasmic sequestration in ductal cells of obese subjects, associated with pronounced islet neogenesis (cytokeratin 19/chromogranin A double labeling). cDNA microarray analysis also showed up-regulation of other genes implicated in islet regeneration, including betacellulin, laminin, TGFa, NeuroD1, Pax6, substantiating the role of the islet neogenesis pathway in human obesity. |
| 1905 | 16026757 | The transcription factor Stat3 is activated by multiple cytokines, including leptin and those signaling through the gp130 receptor. |
| 1906 | 16026757 | In two independent studies, mice in which the Stat3 gene was inactivated using a RIP-Cre transgene led to glucose intolerance, defects in early-phase insulin secretion, and mild obesity [S. |
| 1907 | 16026757 | Hori, Insulin secretory defects and impaired islet architecture in pancreatic beta-cell-specific STAT3 knockout mice, Biochem. |
| 1908 | 16026757 | However, since the RIP-Cre transgene is also expressed in the hypothalamus, and thereby Stat3 was deleted from neurons expressing the leptin receptor, it was not clear as to which of the metabolic defects were due to the loss of Stat3 from beta-cells or the hypothalamus. |
| 1909 | 16026757 | We have addressed this issue through the inactivation of Stat3 from pancreatic beta-cells using a Pdx1-Cre transgene. |
| 1910 | 16026757 | Complete loss of Stat3 was observed in islets from mice, which carry two floxed Stat3 alleles and the Pdx1-Cre transgene. |
| 1911 | 16026757 | The transcription factor Stat3 is activated by multiple cytokines, including leptin and those signaling through the gp130 receptor. |
| 1912 | 16026757 | In two independent studies, mice in which the Stat3 gene was inactivated using a RIP-Cre transgene led to glucose intolerance, defects in early-phase insulin secretion, and mild obesity [S. |
| 1913 | 16026757 | Hori, Insulin secretory defects and impaired islet architecture in pancreatic beta-cell-specific STAT3 knockout mice, Biochem. |
| 1914 | 16026757 | However, since the RIP-Cre transgene is also expressed in the hypothalamus, and thereby Stat3 was deleted from neurons expressing the leptin receptor, it was not clear as to which of the metabolic defects were due to the loss of Stat3 from beta-cells or the hypothalamus. |
| 1915 | 16026757 | We have addressed this issue through the inactivation of Stat3 from pancreatic beta-cells using a Pdx1-Cre transgene. |
| 1916 | 16026757 | Complete loss of Stat3 was observed in islets from mice, which carry two floxed Stat3 alleles and the Pdx1-Cre transgene. |
| 1917 | 16035308 | Six genetic mutations have been described, one of them affecting the glucokinase gene (MODY 2) and the others various transcription factors HNF-1alpha, HNF-4alpha, HNF-1beta, IPF-1 and NeuroD (MODY 1,3,4,5,6, respectively). |
| 1918 | 16035308 | Among the two most frequent forms, MODY 2 (mutation of the glucokinase gene) has a benign clinical evolution whereas MODY 3 (mutation of HNF-1alpha gene) has a much more severe evolution. |
| 1919 | 16046294 | Mechanisms of compensatory beta-cell growth in insulin-resistant rats: roles of Akt kinase. |
| 1920 | 16046294 | In these ZF pups, an augmented survival potential of beta-cells of ZF pups was observed by enhanced activated (phospho-) Akt, phospho-BAD, and Bcl-2 immunoreactivity in the postweaning period. |
| 1921 | 16046294 | During this phase, we also detected an increase in the numbers of small beta-cell clusters among ducts and acini, increased duct pancreatic/duodenal homeobox-1 (PDX-1) immunoreactivity, and an increase in islet number in the ZF rats suggesting duct- and acini-mediated heightened beta-cell neogenesis. |
| 1922 | 16046294 | Interestingly, in young ZF rats, specific cells associated with ducts, acini, and islets exhibited an increased frequency of PDX-1+/phospho-Akt+ staining, indicating a potential role for Akt in beta-cell differentiation. |
| 1923 | 16046294 | Mechanisms of compensatory beta-cell growth in insulin-resistant rats: roles of Akt kinase. |
| 1924 | 16046294 | In these ZF pups, an augmented survival potential of beta-cells of ZF pups was observed by enhanced activated (phospho-) Akt, phospho-BAD, and Bcl-2 immunoreactivity in the postweaning period. |
| 1925 | 16046294 | During this phase, we also detected an increase in the numbers of small beta-cell clusters among ducts and acini, increased duct pancreatic/duodenal homeobox-1 (PDX-1) immunoreactivity, and an increase in islet number in the ZF rats suggesting duct- and acini-mediated heightened beta-cell neogenesis. |
| 1926 | 16046294 | Interestingly, in young ZF rats, specific cells associated with ducts, acini, and islets exhibited an increased frequency of PDX-1+/phospho-Akt+ staining, indicating a potential role for Akt in beta-cell differentiation. |
| 1927 | 16055439 | Insulin gene expression is regulated by pancreatic beta cell-specific factors, PDX-1 and BETA2/E47. |
| 1928 | 16055439 | These two cis-DNA regions, E1 and E2, with an appropriate distance separating them, were mandatory for the synergism, which implicates formation of SREBP-1c.BETA2.E47 complex in a DNA looping structure for efficient recruitment of CREB-binding protein/p300. |
| 1929 | 16055439 | SREBP-1c-mediated activation of the insulin promoter and expression became overt in beta cell lines and isolated islets when endogenous PDX-1 expression was low. |
| 1930 | 16055439 | Insulin gene expression is regulated by pancreatic beta cell-specific factors, PDX-1 and BETA2/E47. |
| 1931 | 16055439 | These two cis-DNA regions, E1 and E2, with an appropriate distance separating them, were mandatory for the synergism, which implicates formation of SREBP-1c.BETA2.E47 complex in a DNA looping structure for efficient recruitment of CREB-binding protein/p300. |
| 1932 | 16055439 | SREBP-1c-mediated activation of the insulin promoter and expression became overt in beta cell lines and isolated islets when endogenous PDX-1 expression was low. |
| 1933 | 16109755 | Islet cell differentiation was studied by the following: (a) X-gal staining after neomycin selection, (b) BrdU (bro-modeoxyuridine) studies, (c) simple and double immunohistochemistry for insulin, C-peptide, and glucose transporter 2 (Glut-2), (d) reverse transcription-polymerase chain reaction for insulin and pancreas duodenum homeobox 1 (PDX-1), (e) insulin and C-peptide content and secretion assays, (f) intraperitoneal glucose tolerance test, (g) electrophysiology (patch-clamp studies in inside-out configuration), and (h) transplantation of differentiated cells under the kidney capsule of streptozotocin-diabetic mice. |
| 1934 | 16109755 | The differentiated ESCs showed the following: changes in the mRNA levels of insulin and PDX-1; coexpression of insulin, C-peptide, and Glut-2; glucose and tolbutamide-dependent insulin and C-peptide release; K-channel activity regulated by ATP; and normalization of blood glucose levels after transplantation into diabetic mice and hyperglycemia after graft removal. |
| 1935 | 16109755 | Islet cell differentiation was studied by the following: (a) X-gal staining after neomycin selection, (b) BrdU (bro-modeoxyuridine) studies, (c) simple and double immunohistochemistry for insulin, C-peptide, and glucose transporter 2 (Glut-2), (d) reverse transcription-polymerase chain reaction for insulin and pancreas duodenum homeobox 1 (PDX-1), (e) insulin and C-peptide content and secretion assays, (f) intraperitoneal glucose tolerance test, (g) electrophysiology (patch-clamp studies in inside-out configuration), and (h) transplantation of differentiated cells under the kidney capsule of streptozotocin-diabetic mice. |
| 1936 | 16109755 | The differentiated ESCs showed the following: changes in the mRNA levels of insulin and PDX-1; coexpression of insulin, C-peptide, and Glut-2; glucose and tolbutamide-dependent insulin and C-peptide release; K-channel activity regulated by ATP; and normalization of blood glucose levels after transplantation into diabetic mice and hyperglycemia after graft removal. |
| 1937 | 16123344 | We have previously demonstrated that the expression of the beta-cell transcription factor pancreatic duodenal homeobox 1 (PDX-1) in human fetal liver cells activates multiple aspects of the beta-cell phenotype. |
| 1938 | 16123344 | Cells cultured with activin A in serum-free medium upregulated expression of NeuroD and Nkx2.2 and downregulated paired box homeotic gene 6 (PAX-6). |
| 1939 | 16123344 | Glucokinase and prohormone convertase 1/3 were also upregulated, whereas pancreatic polypeptide and glucagon as well as liver markers were downregulated. |
| 1940 | 16123346 | Repression of Pdx1 in adult mice impaired expression of insulin and glucagon, leading to diabetes within 14 days. |
| 1941 | 16140554 | Evaluation of sequence variants in the pre-B cell leukemia transcription factor 1 gene: a positional and functional candidate for type 2 diabetes and impaired insulin secretion. |
| 1942 | 16140554 | Pre-B cell leukemia transcription factor 1 (PBX1) encodes a homeodomain containing protein that is essential for pancreatic development and interacts with insulin promoter factor 1 to regulate insulin secretion. |
| 1943 | 16166097 | The transcription factor PDX-1 plays a crucial role during pancreatic development and in the function of insulin-producing beta cells. |
| 1944 | 16166097 | These proteins, Ku70 and Ku80, are regulatory subunits of DNA-dependent protein kinase (DNA-PK). |
| 1945 | 16166097 | We determined that the interaction between PDX-1 and Ku70 or Ku80 is dependent on the homeodomain of PDX-1. |
| 1946 | 16166097 | Most interestingly, we demonstrated in vitro that the DNA-PK phosphorylates PDX-1 on threonine 11. |
| 1947 | 16166097 | However, in response to radiation, which activates DNA-PK, a second form of the PDX-1 protein appears rapidly. |
| 1948 | 16166097 | In correlation with this degradation, we observed a subsequent reduction in the activation of the insulin promoter and a decrease in PDX-1-mediated gene expression, i.e. glut2 and glucokinase. |
| 1949 | 16166097 | Our study demonstrates that radiation, through the activation of DNA-PK, may regulate PDX-1 protein expression. |
| 1950 | 16166097 | The transcription factor PDX-1 plays a crucial role during pancreatic development and in the function of insulin-producing beta cells. |
| 1951 | 16166097 | These proteins, Ku70 and Ku80, are regulatory subunits of DNA-dependent protein kinase (DNA-PK). |
| 1952 | 16166097 | We determined that the interaction between PDX-1 and Ku70 or Ku80 is dependent on the homeodomain of PDX-1. |
| 1953 | 16166097 | Most interestingly, we demonstrated in vitro that the DNA-PK phosphorylates PDX-1 on threonine 11. |
| 1954 | 16166097 | However, in response to radiation, which activates DNA-PK, a second form of the PDX-1 protein appears rapidly. |
| 1955 | 16166097 | In correlation with this degradation, we observed a subsequent reduction in the activation of the insulin promoter and a decrease in PDX-1-mediated gene expression, i.e. glut2 and glucokinase. |
| 1956 | 16166097 | Our study demonstrates that radiation, through the activation of DNA-PK, may regulate PDX-1 protein expression. |
| 1957 | 16166097 | The transcription factor PDX-1 plays a crucial role during pancreatic development and in the function of insulin-producing beta cells. |
| 1958 | 16166097 | These proteins, Ku70 and Ku80, are regulatory subunits of DNA-dependent protein kinase (DNA-PK). |
| 1959 | 16166097 | We determined that the interaction between PDX-1 and Ku70 or Ku80 is dependent on the homeodomain of PDX-1. |
| 1960 | 16166097 | Most interestingly, we demonstrated in vitro that the DNA-PK phosphorylates PDX-1 on threonine 11. |
| 1961 | 16166097 | However, in response to radiation, which activates DNA-PK, a second form of the PDX-1 protein appears rapidly. |
| 1962 | 16166097 | In correlation with this degradation, we observed a subsequent reduction in the activation of the insulin promoter and a decrease in PDX-1-mediated gene expression, i.e. glut2 and glucokinase. |
| 1963 | 16166097 | Our study demonstrates that radiation, through the activation of DNA-PK, may regulate PDX-1 protein expression. |
| 1964 | 16166097 | The transcription factor PDX-1 plays a crucial role during pancreatic development and in the function of insulin-producing beta cells. |
| 1965 | 16166097 | These proteins, Ku70 and Ku80, are regulatory subunits of DNA-dependent protein kinase (DNA-PK). |
| 1966 | 16166097 | We determined that the interaction between PDX-1 and Ku70 or Ku80 is dependent on the homeodomain of PDX-1. |
| 1967 | 16166097 | Most interestingly, we demonstrated in vitro that the DNA-PK phosphorylates PDX-1 on threonine 11. |
| 1968 | 16166097 | However, in response to radiation, which activates DNA-PK, a second form of the PDX-1 protein appears rapidly. |
| 1969 | 16166097 | In correlation with this degradation, we observed a subsequent reduction in the activation of the insulin promoter and a decrease in PDX-1-mediated gene expression, i.e. glut2 and glucokinase. |
| 1970 | 16166097 | Our study demonstrates that radiation, through the activation of DNA-PK, may regulate PDX-1 protein expression. |
| 1971 | 16166097 | The transcription factor PDX-1 plays a crucial role during pancreatic development and in the function of insulin-producing beta cells. |
| 1972 | 16166097 | These proteins, Ku70 and Ku80, are regulatory subunits of DNA-dependent protein kinase (DNA-PK). |
| 1973 | 16166097 | We determined that the interaction between PDX-1 and Ku70 or Ku80 is dependent on the homeodomain of PDX-1. |
| 1974 | 16166097 | Most interestingly, we demonstrated in vitro that the DNA-PK phosphorylates PDX-1 on threonine 11. |
| 1975 | 16166097 | However, in response to radiation, which activates DNA-PK, a second form of the PDX-1 protein appears rapidly. |
| 1976 | 16166097 | In correlation with this degradation, we observed a subsequent reduction in the activation of the insulin promoter and a decrease in PDX-1-mediated gene expression, i.e. glut2 and glucokinase. |
| 1977 | 16166097 | Our study demonstrates that radiation, through the activation of DNA-PK, may regulate PDX-1 protein expression. |
| 1978 | 16166097 | The transcription factor PDX-1 plays a crucial role during pancreatic development and in the function of insulin-producing beta cells. |
| 1979 | 16166097 | These proteins, Ku70 and Ku80, are regulatory subunits of DNA-dependent protein kinase (DNA-PK). |
| 1980 | 16166097 | We determined that the interaction between PDX-1 and Ku70 or Ku80 is dependent on the homeodomain of PDX-1. |
| 1981 | 16166097 | Most interestingly, we demonstrated in vitro that the DNA-PK phosphorylates PDX-1 on threonine 11. |
| 1982 | 16166097 | However, in response to radiation, which activates DNA-PK, a second form of the PDX-1 protein appears rapidly. |
| 1983 | 16166097 | In correlation with this degradation, we observed a subsequent reduction in the activation of the insulin promoter and a decrease in PDX-1-mediated gene expression, i.e. glut2 and glucokinase. |
| 1984 | 16166097 | Our study demonstrates that radiation, through the activation of DNA-PK, may regulate PDX-1 protein expression. |
| 1985 | 16182777 | Cells characterized by a group of markers (Nestin, CK-8, CK-18) and transcription factors (Isl-1, Pdx-1, Pax-4, Ngn-3) important for beta-cell differentiation have been detected in umbilical cord blood. |
| 1986 | 16186387 | Spontaneous differentiation of hESCs under two-dimensional growth conditions resulted in differentiation of Pdx1(+)/Foxa2(+) pancreatic progenitors and Pdx1(+)/Isl1(+) endocrine progenitors but no insulin-producing cells. |
| 1987 | 16186387 | Comparative analysis of the basic characteristics of hESC-derived insulin(+) cell clusters with human adult islets demonstrated that the insulin(+) cells share important features with normal beta-cells, such as synthesis (proinsulin) and processing (C-peptide) of insulin and nuclear localization of key beta-cell transcription factors, including Foxa2, Pdx1, and Isl1. |
| 1988 | 16186387 | Spontaneous differentiation of hESCs under two-dimensional growth conditions resulted in differentiation of Pdx1(+)/Foxa2(+) pancreatic progenitors and Pdx1(+)/Isl1(+) endocrine progenitors but no insulin-producing cells. |
| 1989 | 16186387 | Comparative analysis of the basic characteristics of hESC-derived insulin(+) cell clusters with human adult islets demonstrated that the insulin(+) cells share important features with normal beta-cells, such as synthesis (proinsulin) and processing (C-peptide) of insulin and nuclear localization of key beta-cell transcription factors, including Foxa2, Pdx1, and Isl1. |
| 1990 | 16186810 | Reverted NAKT-15 cells expressed beta-cell transcription factors (Isl-1, Pax 6, Nkx 6.1, Pdx-1), prohormone convertases 1/3 and 2, and secretory granule proteins, and secreted insulin in response to glucose, similar to normal human islets. |
| 1991 | 16280646 | When oxidative stress was induced in vitro in beta cells, the insulin gene promoter activity and mRNA levels were suppressed, accompanied by the reduced activity of pancreatic and duodenal homeobox factor-1 (PDX-1) (also known as IDX-1/STF-1/IPF1), an important transcription factor for the insulin gene. |
| 1992 | 16280646 | The suppression of oxidative stress by a potent antioxidant, N-acetyl-l-cysteine or probucol, led to the recovery of insulin biosynthesis and PDX-1 expression in nuclei and improved glucose tolerance in animal models for type 2 diabetes. |
| 1993 | 16280646 | Furthermore, the addition of a dominant-negative form of c-Jun N-terminal kinase (JNK) inhibited the oxidative stress-induced PDX-1 translocation, suggesting an essential role of JNK in mediating the phenomenon. |
| 1994 | 16280646 | Taken together, the oxidative stress-mediated activation of the JNK pathway leads to nucleocytoplasmic translocation of PDX-1 and thus is likely involved in the progression of beta-cell dysfunction found in diabetes. |
| 1995 | 16280646 | When oxidative stress was induced in vitro in beta cells, the insulin gene promoter activity and mRNA levels were suppressed, accompanied by the reduced activity of pancreatic and duodenal homeobox factor-1 (PDX-1) (also known as IDX-1/STF-1/IPF1), an important transcription factor for the insulin gene. |
| 1996 | 16280646 | The suppression of oxidative stress by a potent antioxidant, N-acetyl-l-cysteine or probucol, led to the recovery of insulin biosynthesis and PDX-1 expression in nuclei and improved glucose tolerance in animal models for type 2 diabetes. |
| 1997 | 16280646 | Furthermore, the addition of a dominant-negative form of c-Jun N-terminal kinase (JNK) inhibited the oxidative stress-induced PDX-1 translocation, suggesting an essential role of JNK in mediating the phenomenon. |
| 1998 | 16280646 | Taken together, the oxidative stress-mediated activation of the JNK pathway leads to nucleocytoplasmic translocation of PDX-1 and thus is likely involved in the progression of beta-cell dysfunction found in diabetes. |
| 1999 | 16280646 | When oxidative stress was induced in vitro in beta cells, the insulin gene promoter activity and mRNA levels were suppressed, accompanied by the reduced activity of pancreatic and duodenal homeobox factor-1 (PDX-1) (also known as IDX-1/STF-1/IPF1), an important transcription factor for the insulin gene. |
| 2000 | 16280646 | The suppression of oxidative stress by a potent antioxidant, N-acetyl-l-cysteine or probucol, led to the recovery of insulin biosynthesis and PDX-1 expression in nuclei and improved glucose tolerance in animal models for type 2 diabetes. |
| 2001 | 16280646 | Furthermore, the addition of a dominant-negative form of c-Jun N-terminal kinase (JNK) inhibited the oxidative stress-induced PDX-1 translocation, suggesting an essential role of JNK in mediating the phenomenon. |
| 2002 | 16280646 | Taken together, the oxidative stress-mediated activation of the JNK pathway leads to nucleocytoplasmic translocation of PDX-1 and thus is likely involved in the progression of beta-cell dysfunction found in diabetes. |
| 2003 | 16280646 | When oxidative stress was induced in vitro in beta cells, the insulin gene promoter activity and mRNA levels were suppressed, accompanied by the reduced activity of pancreatic and duodenal homeobox factor-1 (PDX-1) (also known as IDX-1/STF-1/IPF1), an important transcription factor for the insulin gene. |
| 2004 | 16280646 | The suppression of oxidative stress by a potent antioxidant, N-acetyl-l-cysteine or probucol, led to the recovery of insulin biosynthesis and PDX-1 expression in nuclei and improved glucose tolerance in animal models for type 2 diabetes. |
| 2005 | 16280646 | Furthermore, the addition of a dominant-negative form of c-Jun N-terminal kinase (JNK) inhibited the oxidative stress-induced PDX-1 translocation, suggesting an essential role of JNK in mediating the phenomenon. |
| 2006 | 16280646 | Taken together, the oxidative stress-mediated activation of the JNK pathway leads to nucleocytoplasmic translocation of PDX-1 and thus is likely involved in the progression of beta-cell dysfunction found in diabetes. |
| 2007 | 16293776 | We previously identified Bridge-1 (PSMD9) as a PDZ-domain coregulator that augments insulin gene transcription via interactions with the basic helix-loop-helix transcription factors E12 and E47, and that increases transcriptional activation by the homeodomain transcription factor PDX-1. |
| 2008 | 16293776 | In these studies, we find that transcriptional activation by Bridge-1 can be regulated via interactions with the histone acetyltransferase and nuclear receptor coactivator p300. |
| 2009 | 16293776 | We demonstrate that p300 and Bridge-1 proteins interact in immunopre-cipitation and glutathione-S-transferase (GST) pull-down assays. |
| 2010 | 16293776 | Bridge-1 interacts directly with multiple regions within p300 that encompass C/H1 or C/H2 cysteine- and histidine-rich protein interaction domains and the histone acetyltransferase domain. |
| 2011 | 16309850 | Incretin hormones have trophic effects on beta cell function that can aid prevention and treatment of diabetes. cAMP is the primary mediator of these effects, and has been shown to potentiate glucose-stimulated insulin secretion, promote proper beta cells differentiation by increasing expression of the crucial transcription factor PDX-1, and prevent beta cell apoptosis. cGMP's role in beta cell function has received far less scrutiny, but there is emerging evidence that it may have a trophic impact on beta cell function analogous to that of cAMP. |
| 2012 | 16309850 | An increase in plasma glucose boosts beta cell production of cGMP, which acts as a feed-forward mediator to enhance glucose-stimulated insulin secretion. cGMP also has an anti-apoptotic effect in beta cells, and there is now indirect evidence that it promotes expression of PDX-1. |
| 2013 | 16309850 | Incretin hormones have trophic effects on beta cell function that can aid prevention and treatment of diabetes. cAMP is the primary mediator of these effects, and has been shown to potentiate glucose-stimulated insulin secretion, promote proper beta cells differentiation by increasing expression of the crucial transcription factor PDX-1, and prevent beta cell apoptosis. cGMP's role in beta cell function has received far less scrutiny, but there is emerging evidence that it may have a trophic impact on beta cell function analogous to that of cAMP. |
| 2014 | 16309850 | An increase in plasma glucose boosts beta cell production of cGMP, which acts as a feed-forward mediator to enhance glucose-stimulated insulin secretion. cGMP also has an anti-apoptotic effect in beta cells, and there is now indirect evidence that it promotes expression of PDX-1. |
| 2015 | 16337608 | Microarray analyses of insulin-producing cells exposed to interleukin-1beta+interferon-gamma showed decreased expression of genes related to beta-cell-differentiated functions and increased expression of members of the Notch signaling pathway. |
| 2016 | 16337608 | Transfection of insulin-producing INS-1E cells and primary rat beta-cells with a constitutively active form of the Notch receptor down-regulated Pdx1 and insulin expression in INS-1E cells but not in primary beta-cells. |
| 2017 | 16339272 | Overexpression of Kruppel-like factor 7 regulates adipocytokine gene expressions in human adipocytes and inhibits glucose-induced insulin secretion in pancreatic beta-cell line. |
| 2018 | 16339272 | We have identified Kruppel-like factor 7 (KLF7) as a new candidate for conferring susceptibility to type 2 diabetes. |
| 2019 | 16339272 | In human adipocytes overexpressing KLF7, the expression of adiponectin and leptin was decreased compared with that in control cells, whereas expression of IL-6 was increased. |
| 2020 | 16339272 | In the insulin-secreting cell line (HIT-T15 cells), the expression and glucose-induced secretion of insulin were significantly suppressed in KLF7-overexpressed cells compared with control cells, accompanied by the reduction in the expression of glucose transporter 2, sulfonylurea receptor 1, Kir6.2, and pancreatic-duodenal homeobox factor 1. |
| 2021 | 16339272 | We also found that the overexpression of KLF7 resulted in the decrease of hexokinase 2 expression in smooth muscle cells, and of glucose transporter 2 expression in the HepG2 cells. |
| 2022 | 16339272 | These results suggest that KLF7 may contribute to the pathogenesis of type 2 diabetes through an impairment of insulin biosynthesis and secretion in pancreatic beta-cells and a reduction of insulin sensitivity in peripheral tissues. |
| 2023 | 16380477 | A vHNF1/TCF2-HNF6 cascade regulates the transcription factor network that controls generation of pancreatic precursor cells. |
| 2024 | 16380477 | Hepatocyte nuclear factor-6 (HNF6) is a key player in this network, because it controls the initiation of the expression of pancreatic and duodenal homeobox 1 (Pdx1), the earliest marker of pancreatic precursor cells. |
| 2025 | 16380477 | Among the latter, variant HNF1 (vHNF1)/TCF2, which is expressed before HNF6 in the endoderm, was found to be critical for HNF6 expression. |
| 2026 | 16380477 | Therefore, the sequential activation of vHNF1, HNF6, and Pdx1 in the endoderm appears to control the generation of pancreatic precursors. |
| 2027 | 16380477 | A vHNF1/TCF2-HNF6 cascade regulates the transcription factor network that controls generation of pancreatic precursor cells. |
| 2028 | 16380477 | Hepatocyte nuclear factor-6 (HNF6) is a key player in this network, because it controls the initiation of the expression of pancreatic and duodenal homeobox 1 (Pdx1), the earliest marker of pancreatic precursor cells. |
| 2029 | 16380477 | Among the latter, variant HNF1 (vHNF1)/TCF2, which is expressed before HNF6 in the endoderm, was found to be critical for HNF6 expression. |
| 2030 | 16380477 | Therefore, the sequential activation of vHNF1, HNF6, and Pdx1 in the endoderm appears to control the generation of pancreatic precursors. |
| 2031 | 16435884 | Conditional expression of Smad7 in pancreatic beta cells disrupts TGF-beta signaling and induces reversible diabetes mellitus. |
| 2032 | 16435884 | Here we describe a conditional system for expressing Smad7, a potent inhibitor of TGF-beta signaling, to identify distinct roles for this pathway in adult and embryonic beta cells. |
| 2033 | 16435884 | Smad7 expression in Pdx1+ embryonic pancreas cells resulted in striking embryonic beta cell hypoplasia and neonatal lethality. |
| 2034 | 16435884 | Conditional expression of Smad7 in adult Pdx1+ cells reduced detectable beta cell expression of MafA, menin, and other factors that regulate beta cell function. |
| 2035 | 16435884 | Reduced pancreatic insulin content and hypoinsulinemia produced overt diabetes that was fully reversed upon resumption of islet TGF-beta signaling. |
| 2036 | 16435884 | Conditional expression of Smad7 in pancreatic beta cells disrupts TGF-beta signaling and induces reversible diabetes mellitus. |
| 2037 | 16435884 | Here we describe a conditional system for expressing Smad7, a potent inhibitor of TGF-beta signaling, to identify distinct roles for this pathway in adult and embryonic beta cells. |
| 2038 | 16435884 | Smad7 expression in Pdx1+ embryonic pancreas cells resulted in striking embryonic beta cell hypoplasia and neonatal lethality. |
| 2039 | 16435884 | Conditional expression of Smad7 in adult Pdx1+ cells reduced detectable beta cell expression of MafA, menin, and other factors that regulate beta cell function. |
| 2040 | 16435884 | Reduced pancreatic insulin content and hypoinsulinemia produced overt diabetes that was fully reversed upon resumption of islet TGF-beta signaling. |
| 2041 | 16443759 | Although bone marrow cells expressing GFP under the ubiquitously expressed beta-actin promoter efficiently engrafted the pancreas of normal and hyperglycemic mice, virtually all expressed CD45 and Mac-1/Gr-1, demonstrating that they adopt a hematopoietic rather than beta-cell fate, a finding further substantiated by the complete absence of GFP(+) cells expressing insulin and the beta-cell transcription factors pancreatic duodenal homeobox factor-1 and homeodomain protein. |
| 2042 | 16449294 | Activation of the Reg family genes by pancreatic-specific IGF-I gene deficiency and after streptozotocin-induced diabetes in mouse pancreas. |
| 2043 | 16449294 | We have recently reported that Pdx1-Cre-mediated whole pancreas inactivation of IGF-I gene [in pancreatic-specific IGF-I gene-deficient (PID) mice] results in increased beta-cell mass and significant protection against both type 1 and type 2 diabetes. |
| 2044 | 16449294 | Because the phenotype is unlikely a direct consequence of IGF-I deficiency, the present study was designed to explore possible activation of proislet factors in PID mice by using a whole genome DNA microarray. |
| 2045 | 16449294 | Immunohistochemistry revealed increased Reg proteins in exocrine as well as endocrine pancreas and suggested their potential role in beta-cell neogenesis in PID or T1D mice. |
| 2046 | 16449294 | These uncharacterized Reg proteins may play a similar but more potent role, not only in normal islet cell growth in PID mice, but also in islet cell regeneration after T1D. |
| 2047 | 16460677 | Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells. |
| 2048 | 16460677 | During the proliferation period, the cells expressed the stem cell markers nestin, ABCG2, SCF, Thy-1 as well as the pancreatic endocrine transcription factor Isl-1. |
| 2049 | 16460677 | Using quantitative PCR a down-regulation of ABCG2 and up-regulation of pancreatic developmental transcription factors Isl-1, Ipf-1, and Ngn3 were observed together with induction of the islet hormones insulin, glucagon, and somatostatin. |
| 2050 | 16469158 | High-fat feeding reduces the expression of GLUT-2 and the glycolytic enzyme glucokinase (GK). |
| 2051 | 16469158 | The transcription factor, pancreatic duodenal homeobox-1 (Pdx-1), is important for beta-cell maintenance. |
| 2052 | 16469158 | The aim of the present study was to determine, in weanling Wistar rats, the effect of a maternal high-fat diet (HFD) during defined periods of gestation and lactation, on body weight, circulating glucose and insulin concentrations, and the expression of GLUT-2, GK and Pdx-1. |
| 2053 | 16469158 | Pancreatic sections, immunostained for GLUT-2, GK or Pdx-1, were assessed by image analysis. |
| 2054 | 16469158 | High-fat feeding reduces the expression of GLUT-2 and the glycolytic enzyme glucokinase (GK). |
| 2055 | 16469158 | The transcription factor, pancreatic duodenal homeobox-1 (Pdx-1), is important for beta-cell maintenance. |
| 2056 | 16469158 | The aim of the present study was to determine, in weanling Wistar rats, the effect of a maternal high-fat diet (HFD) during defined periods of gestation and lactation, on body weight, circulating glucose and insulin concentrations, and the expression of GLUT-2, GK and Pdx-1. |
| 2057 | 16469158 | Pancreatic sections, immunostained for GLUT-2, GK or Pdx-1, were assessed by image analysis. |
| 2058 | 16469158 | High-fat feeding reduces the expression of GLUT-2 and the glycolytic enzyme glucokinase (GK). |
| 2059 | 16469158 | The transcription factor, pancreatic duodenal homeobox-1 (Pdx-1), is important for beta-cell maintenance. |
| 2060 | 16469158 | The aim of the present study was to determine, in weanling Wistar rats, the effect of a maternal high-fat diet (HFD) during defined periods of gestation and lactation, on body weight, circulating glucose and insulin concentrations, and the expression of GLUT-2, GK and Pdx-1. |
| 2061 | 16469158 | Pancreatic sections, immunostained for GLUT-2, GK or Pdx-1, were assessed by image analysis. |
| 2062 | 16497530 | The human forkhead box O1A (FOXO1A) gene on chromosome 13q14.1 is a key transcription factor in insulin signaling in liver and adipose tissue and plays a central role in the regulation of key pancreatic beta-cell genes including IPF1. |
| 2063 | 16497530 | We hypothesized that sequence variants of FOXO1A contribute to the observed defects in hepatic and peripheral insulin action and altered beta-cell compensation that characterize type 2 diabetes (T2DM). |
| 2064 | 16504534 | A more promising gene therapy approach has been to express pancreatic endocrine developmental factors, such as PDX-1, NeuroD/BETA2 and Neurogenin 3, to promote differentiation of non-endocrine cells towards a beta cell or islet phenotype, enabling these cells to synthesize and secrete insulin in a glucose-regulated manner. |
| 2065 | 16505238 | MafA expression and insulin promoter activity are induced by nicotinamide and related compounds in INS-1 pancreatic beta-cells. |
| 2066 | 16505238 | Exposure of INS-1 beta-cells to elevated glucose leads to reduced insulin gene transcription, and this is associated with diminished binding of pancreatic duodenal homeobox factor 1 (PDX-1) and mammalian homologue of avian MafA/l-Maf (MafA). |
| 2067 | 16505238 | Nicotinamide and other low-potency poly(ADP-ribose) polymerase (PARP) inhibitors were thus tested for their ability to restore insulin promoter activity. |
| 2068 | 16505238 | The low-potency PARP inhibitors nicotinamide, 3-aminobenzamide, or PD128763 increased expression of a human insulin reporter gene suppressed by elevated glucose. |
| 2069 | 16505238 | In contrast, the potent PARP-1 inhibitors PJ34 or INO-1001 had no effect on promoter activity. |
| 2070 | 16505238 | Site-directed mutations of the human insulin promoter mapped the low-potency PARP inhibitor response to the C1 element, which serves as a MafA binding site. |
| 2071 | 16505238 | Low-potency PARP inhibitors restored MafA mRNA and protein levels, but they had no affect on PDX-1 protein levels or binding activity. |
| 2072 | 16505238 | Increased MafA expression by low-potency PARP inhibitors was independent of increased MafA protein or mRNA stability. |
| 2073 | 16505238 | These data suggest that low-potency PARP inhibitors increase insulin biosynthesis, in part, through a mechanism involving increased MafA gene transcription. |
| 2074 | 16505238 | MafA expression and insulin promoter activity are induced by nicotinamide and related compounds in INS-1 pancreatic beta-cells. |
| 2075 | 16505238 | Exposure of INS-1 beta-cells to elevated glucose leads to reduced insulin gene transcription, and this is associated with diminished binding of pancreatic duodenal homeobox factor 1 (PDX-1) and mammalian homologue of avian MafA/l-Maf (MafA). |
| 2076 | 16505238 | Nicotinamide and other low-potency poly(ADP-ribose) polymerase (PARP) inhibitors were thus tested for their ability to restore insulin promoter activity. |
| 2077 | 16505238 | The low-potency PARP inhibitors nicotinamide, 3-aminobenzamide, or PD128763 increased expression of a human insulin reporter gene suppressed by elevated glucose. |
| 2078 | 16505238 | In contrast, the potent PARP-1 inhibitors PJ34 or INO-1001 had no effect on promoter activity. |
| 2079 | 16505238 | Site-directed mutations of the human insulin promoter mapped the low-potency PARP inhibitor response to the C1 element, which serves as a MafA binding site. |
| 2080 | 16505238 | Low-potency PARP inhibitors restored MafA mRNA and protein levels, but they had no affect on PDX-1 protein levels or binding activity. |
| 2081 | 16505238 | Increased MafA expression by low-potency PARP inhibitors was independent of increased MafA protein or mRNA stability. |
| 2082 | 16505238 | These data suggest that low-potency PARP inhibitors increase insulin biosynthesis, in part, through a mechanism involving increased MafA gene transcription. |
| 2083 | 16522740 | Analysis of the INGAP promoter suggested that candidate regulators of INGAP expression include the transcription factors PDX-1, NeuroD, PAN-1, STAT and AP-1. |
| 2084 | 16522740 | Induction of AP-1 activity or STAT activity using PMA or LIF stimulation respectively, or direct expression of PAN-1 specifically up-regulates INGAP promoter activity. |
| 2085 | 16522740 | In contrast, co-expression of PDX-1 but not NeuroD inhibits activation of the INGAP-promoter driven by PAN-1, PMA or LIF stimulation. |
| 2086 | 16522740 | Analysis of the INGAP promoter suggested that candidate regulators of INGAP expression include the transcription factors PDX-1, NeuroD, PAN-1, STAT and AP-1. |
| 2087 | 16522740 | Induction of AP-1 activity or STAT activity using PMA or LIF stimulation respectively, or direct expression of PAN-1 specifically up-regulates INGAP promoter activity. |
| 2088 | 16522740 | In contrast, co-expression of PDX-1 but not NeuroD inhibits activation of the INGAP-promoter driven by PAN-1, PMA or LIF stimulation. |
| 2089 | 16543365 | Regulation of insulin gene transcription by the immediate-early growth response gene Egr-1. |
| 2090 | 16543365 | Changes in extracellular glucose levels regulate the expression of the immediate-early response gene and zinc finger transcription factor early growth response-1 (Egr-1) in insulin-producing pancreatic beta-cells, but key target genes of Egr-1 in the endocrine pancreas have not been identified. |
| 2091 | 16543365 | We found that overexpression of Egr-1 in clonal (INS-1) beta-cells increased transcriptional activation of the rat insulin I promoter. |
| 2092 | 16543365 | In contrast, reductions in Egr-1 expression levels or function with the introduction of either small interfering RNA targeted to Egr-1 (siEgr-1) or a dominant-negative form of Egr-1 decreased insulin promoter activation, and siEgr-1 suppressed insulin gene expression. |
| 2093 | 16543365 | Egr-1 did not directly interact with insulin promoter sequences, and mutagenesis of a potential G box recognition sequence for Egr-1 did not impair the Egr-1 responsiveness of the insulin promoter, suggesting that regulation of insulin gene expression by Egr-1 is probably mediated through additional transcription factors. |
| 2094 | 16543365 | Overexpression of Egr-1 increased, and reduction of Egr-1 expression decreased, transcriptional activation of the glucose-responsive FarFlat minienhancer within the rat insulin I promoter despite the absence of demonstrable Egr-1-binding activity to FarFlat sequences. |
| 2095 | 16543365 | Notably, augmenting Egr-1 expression levels in insulin-producing cells increased the mRNA and protein expression levels of pancreas duodenum homeobox-1 (PDX-1), a major transcriptional regulator of glucose-responsive activation of the insulin gene. |
| 2096 | 16543365 | Increasing Egr-1 expression levels enhanced PDX-1 binding to insulin promoter sequences, whereas mutagenesis of PDX-1-binding sites reduced the capacity of Egr-1 to activate the insulin promoter. |
| 2097 | 16543365 | We propose that changes in Egr-1 expression levels in response to extracellular signals, including glucose, can regulate PDX-1 expression and insulin production in pancreatic beta-cells. |
| 2098 | 16543365 | Regulation of insulin gene transcription by the immediate-early growth response gene Egr-1. |
| 2099 | 16543365 | Changes in extracellular glucose levels regulate the expression of the immediate-early response gene and zinc finger transcription factor early growth response-1 (Egr-1) in insulin-producing pancreatic beta-cells, but key target genes of Egr-1 in the endocrine pancreas have not been identified. |
| 2100 | 16543365 | We found that overexpression of Egr-1 in clonal (INS-1) beta-cells increased transcriptional activation of the rat insulin I promoter. |
| 2101 | 16543365 | In contrast, reductions in Egr-1 expression levels or function with the introduction of either small interfering RNA targeted to Egr-1 (siEgr-1) or a dominant-negative form of Egr-1 decreased insulin promoter activation, and siEgr-1 suppressed insulin gene expression. |
| 2102 | 16543365 | Egr-1 did not directly interact with insulin promoter sequences, and mutagenesis of a potential G box recognition sequence for Egr-1 did not impair the Egr-1 responsiveness of the insulin promoter, suggesting that regulation of insulin gene expression by Egr-1 is probably mediated through additional transcription factors. |
| 2103 | 16543365 | Overexpression of Egr-1 increased, and reduction of Egr-1 expression decreased, transcriptional activation of the glucose-responsive FarFlat minienhancer within the rat insulin I promoter despite the absence of demonstrable Egr-1-binding activity to FarFlat sequences. |
| 2104 | 16543365 | Notably, augmenting Egr-1 expression levels in insulin-producing cells increased the mRNA and protein expression levels of pancreas duodenum homeobox-1 (PDX-1), a major transcriptional regulator of glucose-responsive activation of the insulin gene. |
| 2105 | 16543365 | Increasing Egr-1 expression levels enhanced PDX-1 binding to insulin promoter sequences, whereas mutagenesis of PDX-1-binding sites reduced the capacity of Egr-1 to activate the insulin promoter. |
| 2106 | 16543365 | We propose that changes in Egr-1 expression levels in response to extracellular signals, including glucose, can regulate PDX-1 expression and insulin production in pancreatic beta-cells. |
| 2107 | 16543365 | Regulation of insulin gene transcription by the immediate-early growth response gene Egr-1. |
| 2108 | 16543365 | Changes in extracellular glucose levels regulate the expression of the immediate-early response gene and zinc finger transcription factor early growth response-1 (Egr-1) in insulin-producing pancreatic beta-cells, but key target genes of Egr-1 in the endocrine pancreas have not been identified. |
| 2109 | 16543365 | We found that overexpression of Egr-1 in clonal (INS-1) beta-cells increased transcriptional activation of the rat insulin I promoter. |
| 2110 | 16543365 | In contrast, reductions in Egr-1 expression levels or function with the introduction of either small interfering RNA targeted to Egr-1 (siEgr-1) or a dominant-negative form of Egr-1 decreased insulin promoter activation, and siEgr-1 suppressed insulin gene expression. |
| 2111 | 16543365 | Egr-1 did not directly interact with insulin promoter sequences, and mutagenesis of a potential G box recognition sequence for Egr-1 did not impair the Egr-1 responsiveness of the insulin promoter, suggesting that regulation of insulin gene expression by Egr-1 is probably mediated through additional transcription factors. |
| 2112 | 16543365 | Overexpression of Egr-1 increased, and reduction of Egr-1 expression decreased, transcriptional activation of the glucose-responsive FarFlat minienhancer within the rat insulin I promoter despite the absence of demonstrable Egr-1-binding activity to FarFlat sequences. |
| 2113 | 16543365 | Notably, augmenting Egr-1 expression levels in insulin-producing cells increased the mRNA and protein expression levels of pancreas duodenum homeobox-1 (PDX-1), a major transcriptional regulator of glucose-responsive activation of the insulin gene. |
| 2114 | 16543365 | Increasing Egr-1 expression levels enhanced PDX-1 binding to insulin promoter sequences, whereas mutagenesis of PDX-1-binding sites reduced the capacity of Egr-1 to activate the insulin promoter. |
| 2115 | 16543365 | We propose that changes in Egr-1 expression levels in response to extracellular signals, including glucose, can regulate PDX-1 expression and insulin production in pancreatic beta-cells. |
| 2116 | 16549443 | Glucose is the major physiologic regulator of insulin gene expression; it coordinately controls the recruitment of transcription factors [e.g., pancreatic/duodenal homeobox-1 (PDX-1), mammalian homologue of avian MafA/L-Maf (MafA), Beta2/Neuro D (B2), the rate of transcription, and the stability of insulin mRNA. |
| 2117 | 16549443 | The mechanisms of glucotoxicity, which involve decreased binding activities of PDX-1 and MafA and increased activity of C/EBPbeta, are mediated by high-glucose-induced generation of oxidative stress. |
| 2118 | 16549443 | On the other hand, lipotoxicity is mediated by de novo ceramide synthesis and involves inhibition of PDX-1 nuclear translocation and MafA gene expression. |
| 2119 | 16549443 | Glucose is the major physiologic regulator of insulin gene expression; it coordinately controls the recruitment of transcription factors [e.g., pancreatic/duodenal homeobox-1 (PDX-1), mammalian homologue of avian MafA/L-Maf (MafA), Beta2/Neuro D (B2), the rate of transcription, and the stability of insulin mRNA. |
| 2120 | 16549443 | The mechanisms of glucotoxicity, which involve decreased binding activities of PDX-1 and MafA and increased activity of C/EBPbeta, are mediated by high-glucose-induced generation of oxidative stress. |
| 2121 | 16549443 | On the other hand, lipotoxicity is mediated by de novo ceramide synthesis and involves inhibition of PDX-1 nuclear translocation and MafA gene expression. |
| 2122 | 16549443 | Glucose is the major physiologic regulator of insulin gene expression; it coordinately controls the recruitment of transcription factors [e.g., pancreatic/duodenal homeobox-1 (PDX-1), mammalian homologue of avian MafA/L-Maf (MafA), Beta2/Neuro D (B2), the rate of transcription, and the stability of insulin mRNA. |
| 2123 | 16549443 | The mechanisms of glucotoxicity, which involve decreased binding activities of PDX-1 and MafA and increased activity of C/EBPbeta, are mediated by high-glucose-induced generation of oxidative stress. |
| 2124 | 16549443 | On the other hand, lipotoxicity is mediated by de novo ceramide synthesis and involves inhibition of PDX-1 nuclear translocation and MafA gene expression. |
| 2125 | 16580660 | A switch from MafB to MafA expression accompanies differentiation to pancreatic beta-cells. |
| 2126 | 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. |
| 2127 | 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. |
| 2128 | 16580660 | Ectopically expressed large-Maf factors, MafA, MafB, or cMaf, induced expression from insulin and glucagon reporter constructs, demonstrating a redundancy in their function. |
| 2129 | 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. |
| 2130 | 16580660 | Furthermore, the MafB to MafA transition follows induction of PDX-1 expression (Pdx-1(high)) in MafB+ Ins+ cells. |
| 2131 | 16580660 | A switch from MafB to MafA expression accompanies differentiation to pancreatic beta-cells. |
| 2132 | 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. |
| 2133 | 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. |
| 2134 | 16580660 | Ectopically expressed large-Maf factors, MafA, MafB, or cMaf, induced expression from insulin and glucagon reporter constructs, demonstrating a redundancy in their function. |
| 2135 | 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. |
| 2136 | 16580660 | Furthermore, the MafB to MafA transition follows induction of PDX-1 expression (Pdx-1(high)) in MafB+ Ins+ cells. |
| 2137 | 16611688 | Stabilization of beta-catenin impacts pancreas growth. |
| 2138 | 16611688 | A recent study has shown that deletion of beta-catenin within the pancreatic epithelium results in a loss of pancreas mass. |
| 2139 | 16611688 | Here, we show that ectopic stabilization of beta-catenin within mouse pancreatic epithelium can have divergent effects on both organ formation and growth. |
| 2140 | 16611688 | Robust stabilization of beta-catenin during early organogenesis drives changes in hedgehog and Fgf10 signaling and induces a loss of Pdx1 expression in early pancreatic progenitor cells. |
| 2141 | 16611688 | By contrast, inducing the stabilized form of beta-catenin at a later time point in pancreas development causes enhanced proliferation that results in a dramatic increase in pancreas organ size. |
| 2142 | 16611688 | Taken together, these data suggest a previously unappreciated temporal/spatial role for beta-catenin signaling in the regulation of pancreas organ growth. |
| 2143 | 16612121 | To investigate whether this is also the case in human pancreatic development, we studied the expression of the glucocorticoid receptor and that of the transcription factor Pdx-1 on pancreatic specimens from very early to late stages of development of the human embryo. |
| 2144 | 16612121 | In terms of beta-cell ontogeny, expression of the glucocorticoid receptor in the pancreas coincides with that of the transcription factor Pdx-1 in beta cells. |
| 2145 | 16612121 | To investigate whether this is also the case in human pancreatic development, we studied the expression of the glucocorticoid receptor and that of the transcription factor Pdx-1 on pancreatic specimens from very early to late stages of development of the human embryo. |
| 2146 | 16612121 | In terms of beta-cell ontogeny, expression of the glucocorticoid receptor in the pancreas coincides with that of the transcription factor Pdx-1 in beta cells. |
| 2147 | 16630561 | SHB and angiogenic factors promote ES cell differentiation to insulin-producing cells. |
| 2148 | 16630561 | Moreover, overexpression of SHB as well as culture of EBs in presence of the angiogenic growth factors PDGF or VEGF enhanced the expression of PDX-1 and/or insulin mRNA. |
| 2149 | 16630561 | Finally, expression of GFP under control of the PDX-1 promoter in EBs allowed for the enrichment by FACS of cells expressing PDX-1, C-peptide, and insulin as determined by immunofluorescence. |
| 2150 | 16630561 | It is concluded that SHB and angiogenic factors promote the development of cells expressing PDX-1 and insulin in EBs and that such cells can be separated by FACS. |
| 2151 | 16630561 | SHB and angiogenic factors promote ES cell differentiation to insulin-producing cells. |
| 2152 | 16630561 | Moreover, overexpression of SHB as well as culture of EBs in presence of the angiogenic growth factors PDGF or VEGF enhanced the expression of PDX-1 and/or insulin mRNA. |
| 2153 | 16630561 | Finally, expression of GFP under control of the PDX-1 promoter in EBs allowed for the enrichment by FACS of cells expressing PDX-1, C-peptide, and insulin as determined by immunofluorescence. |
| 2154 | 16630561 | It is concluded that SHB and angiogenic factors promote the development of cells expressing PDX-1 and insulin in EBs and that such cells can be separated by FACS. |
| 2155 | 16630561 | SHB and angiogenic factors promote ES cell differentiation to insulin-producing cells. |
| 2156 | 16630561 | Moreover, overexpression of SHB as well as culture of EBs in presence of the angiogenic growth factors PDGF or VEGF enhanced the expression of PDX-1 and/or insulin mRNA. |
| 2157 | 16630561 | Finally, expression of GFP under control of the PDX-1 promoter in EBs allowed for the enrichment by FACS of cells expressing PDX-1, C-peptide, and insulin as determined by immunofluorescence. |
| 2158 | 16630561 | It is concluded that SHB and angiogenic factors promote the development of cells expressing PDX-1 and insulin in EBs and that such cells can be separated by FACS. |
| 2159 | 16705146 | Here, we characterized renal changes in the pdx1(PB)-HNF6 transgenic mouse that exhibits beta-cell dysfunction and nonobese hypoinsulinemic diabetes. |
| 2160 | 16705146 | The HNF6 males exhibited albuminuria as early as 10 wk of age, and the urinary albumin excretion increased with age, exceeding 150 microg/24 h at 11 mo of age. |
| 2161 | 16705146 | Immunohistochemistry showed accumulation of type IV collagen and TGF-beta1 in the mesangial area. |
| 2162 | 16713999 | Multipotential nestin and Isl-1 positive mesenchymal stem cells isolated from human pancreatic islets. |
| 2163 | 16713999 | Mesenchymal cells in the developing pancreas express the neural stem cell marker nestin and the transcription factor islet-1 (Isl-1). |
| 2164 | 16713999 | They are positive for Isl-1 and nestin and have the potential to adopt a pancreatic endocrine phenotype with expression of critical transcription factors including Ipf-1, Isl-1, Ngn-3, Pax4, Pax6, Nkx2.2, and Nkx6.1 as well as the islet hormones insulin, glucagon, and somatostatin. |
| 2165 | 16713999 | In conclusion, cultured pancreatic islets contain nestin and Isl-1 positive mesenchymal stem cells with multipotential developmental capacity. |
| 2166 | 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. |
| 2167 | 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. |
| 2168 | 16804060 | Insulin-positive cells and pancreatic duodenal homeobox 1 (PDX1)-positive cells both were clearly increased in the older compared with the younger transgenic mice. |
| 2169 | 16804060 | In addition, a subset of the DBA-labeled cells was positive for PDX1, insulin, glucagon, somatostatin, or pancreatic polypeptide. |
| 2170 | 16804060 | Insulin-positive cells and pancreatic duodenal homeobox 1 (PDX1)-positive cells both were clearly increased in the older compared with the younger transgenic mice. |
| 2171 | 16804060 | In addition, a subset of the DBA-labeled cells was positive for PDX1, insulin, glucagon, somatostatin, or pancreatic polypeptide. |
| 2172 | 16814095 | The molecular mechanisms involve the development of decreased levels of two very important insulin promoter transcription factors, PDX-1 and MafA. |
| 2173 | 16822955 | Although beta-cell-related gene expression (PDX-1, proinsulin I, GLUT2, glucokinase, amylin) and function (insulin content and secretion) are slightly reduced during p8 overexpression, removal of IPTG reverses beta-cell function within 24 h to normal levels. |
| 2174 | 16873704 | We examined the association of variants in genes encoding several transcription factors (TCF1, TCF2, HNF4A, ISL1, IPF1, NEUROG3, PAX6, NKX2-2, NKX6-1, and NEUROD1) and genes encoding the ATP-sensitive K(+) channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) with type 2 diabetes in a Japanese cohort of 2,834 subjects. |
| 2175 | 16887799 | Neuronal dysfunction in Alzheimer patients has been linked to overactivity of the cyclin-dependent kinase 5 (CDK5) and its activator p35. |
| 2176 | 16887799 | Further, glucose enhances p35 gene expression, promoting the formation of active p35/CDK5 complexes that regulate the expression of the insulin gene. |
| 2177 | 16887799 | We therefore postulated that CDK5 and p35 may be responsible for this beta cell impairment and that inhibition of CDK5 might have a beneficial effect. |
| 2178 | 16887799 | Inhibition of CDK5 prevented this decrease of insulin gene expression. |
| 2179 | 16887799 | We used DNA binding (gel shift) assays and Western immunoblots to demonstrate that cellular levels of the transcription factor PDX-1, normally decreased by glucotoxicity, were preserved with CDK5 inhibition, as was the binding of PDX-1 to the insulin promoter. |
| 2180 | 16887799 | Analyses of nuclear and cytoplasmic PDX-1 protein levels revealed that CDK5 inhibition restores nuclear PDX-1, without affecting its cytoplasmic concentration, suggesting that CDK5 regulates the nuclear/cytoplasm partitioning of PDX-1. |
| 2181 | 16887799 | Using a Myc-tagged PDX-1 construct, we showed that the translocation of PDX-1 from the nucleus to the cytoplasm during glucotoxic conditions was prevented when CDK5 was inhibited. |
| 2182 | 16887799 | Neuronal dysfunction in Alzheimer patients has been linked to overactivity of the cyclin-dependent kinase 5 (CDK5) and its activator p35. |
| 2183 | 16887799 | Further, glucose enhances p35 gene expression, promoting the formation of active p35/CDK5 complexes that regulate the expression of the insulin gene. |
| 2184 | 16887799 | We therefore postulated that CDK5 and p35 may be responsible for this beta cell impairment and that inhibition of CDK5 might have a beneficial effect. |
| 2185 | 16887799 | Inhibition of CDK5 prevented this decrease of insulin gene expression. |
| 2186 | 16887799 | We used DNA binding (gel shift) assays and Western immunoblots to demonstrate that cellular levels of the transcription factor PDX-1, normally decreased by glucotoxicity, were preserved with CDK5 inhibition, as was the binding of PDX-1 to the insulin promoter. |
| 2187 | 16887799 | Analyses of nuclear and cytoplasmic PDX-1 protein levels revealed that CDK5 inhibition restores nuclear PDX-1, without affecting its cytoplasmic concentration, suggesting that CDK5 regulates the nuclear/cytoplasm partitioning of PDX-1. |
| 2188 | 16887799 | Using a Myc-tagged PDX-1 construct, we showed that the translocation of PDX-1 from the nucleus to the cytoplasm during glucotoxic conditions was prevented when CDK5 was inhibited. |
| 2189 | 16887799 | Neuronal dysfunction in Alzheimer patients has been linked to overactivity of the cyclin-dependent kinase 5 (CDK5) and its activator p35. |
| 2190 | 16887799 | Further, glucose enhances p35 gene expression, promoting the formation of active p35/CDK5 complexes that regulate the expression of the insulin gene. |
| 2191 | 16887799 | We therefore postulated that CDK5 and p35 may be responsible for this beta cell impairment and that inhibition of CDK5 might have a beneficial effect. |
| 2192 | 16887799 | Inhibition of CDK5 prevented this decrease of insulin gene expression. |
| 2193 | 16887799 | We used DNA binding (gel shift) assays and Western immunoblots to demonstrate that cellular levels of the transcription factor PDX-1, normally decreased by glucotoxicity, were preserved with CDK5 inhibition, as was the binding of PDX-1 to the insulin promoter. |
| 2194 | 16887799 | Analyses of nuclear and cytoplasmic PDX-1 protein levels revealed that CDK5 inhibition restores nuclear PDX-1, without affecting its cytoplasmic concentration, suggesting that CDK5 regulates the nuclear/cytoplasm partitioning of PDX-1. |
| 2195 | 16887799 | Using a Myc-tagged PDX-1 construct, we showed that the translocation of PDX-1 from the nucleus to the cytoplasm during glucotoxic conditions was prevented when CDK5 was inhibited. |
| 2196 | 16890895 | Persistent expression of the pancreatic duodenal homeobox-1 (Pdx1) transcription factor or its super-active form Pdx1-VP16 fusion protein in hepatic cells reprograms these cells into pancreatic beta-cell precursors. |
| 2197 | 16894468 | A stepwise forward selection procedure demonstrated that IPF1, MTHFR, and LPL genotypes significantly affected the prevalence of myocardial infarction. |
| 2198 | 16894468 | The genotypes for MTHFR, LPL, and IPF1 may prove reliable for assessment of genetic risk for myocardial infarction. |
| 2199 | 16894468 | A stepwise forward selection procedure demonstrated that IPF1, MTHFR, and LPL genotypes significantly affected the prevalence of myocardial infarction. |
| 2200 | 16894468 | The genotypes for MTHFR, LPL, and IPF1 may prove reliable for assessment of genetic risk for myocardial infarction. |
| 2201 | 16904980 | Forced expression of PDX-1 induces insulin production in intestinal epithelia. |
| 2202 | 16917892 | Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha (HNF1A) and 4 alpha (HNF4A) in maturity-onset diabetes of the young. |
| 2203 | 16917892 | MODY is both clinically and genetically heterogeneous, with six different genes identified to date; glucokinase (GCK), hepatocyte nuclear factor-1 alpha (HNF1A, or TCF1), hepatocyte nuclear factor-4 alpha (HNF4A), insulin promoter factor-1 (IPF1 or PDX1), hepatocyte nuclear factor-1 beta (HNF1B or TCF2), and neurogenic differentiation 1 (NEUROD1). |
| 2204 | 16917892 | Mutations in the HNF1A gene are a common cause of MODY in the majority of populations studied. |
| 2205 | 16917892 | Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. |
| 2206 | 16917892 | The identification of an HNF1A or 4A gene mutation confirms a diagnosis of MODY and has important implications for clinical management. |
| 2207 | 16936209 | RNA of Pdx-1, Glut-2, and Gck was detectable by RT-PCR in whole thymus but not in the clones, suggesting thymic proinsulin expression is Pdx-1 independent and that Pdx-1, Glut-2, and Gck are likely expressed in the thymus as antigens, not as regulatory molecules. |
| 2208 | 16938896 | Glucagon-like peptide 1 (GLP-1) is a hormone that has received significant attention as a therapy for diabetes because of its ability to stimulate insulin biosynthesis and release and to promote growth and survival of insulin-producing beta cells. |
| 2209 | 16938896 | While GLP-1 is produced from the proglucagon precursor by means of prohormone convertase (PC) 1/3 activity in enteroendocrine L cells, the same precursor is differentially processed by PC2 in pancreatic islet alpha cells to release glucagon, leaving GLP-1 trapped within a larger fragment with no known function. |
| 2210 | 16938896 | We hypothesized that we could induce GLP-1 production directly within pancreatic islets by means of delivery of PC1/3 and, further, that this intervention would improve the viability and function of islets. |
| 2211 | 16938896 | Here, we show that adenovirus-mediated expression of PC1/3 in alpha cells increases islet GLP-1 secretion, resulting in improved glucose-stimulated insulin secretion and enhanced survival in response to cytokine treatment. |
| 2212 | 16938896 | PC1/3 expression in alpha cells also improved performance after islet transplantation in a mouse model of type 1 diabetes, possibly by enhancing nuclear Pdx1 and insulin content of islet beta cells. |
| 2213 | 16962573 | These results reveal a role for distal cis-regulatory elements in achieving the correct level of extra-pancreatic Pdx1 expression, which is necessary for the production of duodenal GIP cells and stomach gastrin cells. |
| 2214 | 16968152 | Glucagon-like peptide-1 differentiation of primate embryonic stem cells into insulin-producing cells. |
| 2215 | 16968152 | The present study was performed to determine whether glucagon-like peptide-1 (GLP-1) stimulates differentiation of nestin-selected embryonic stem cells into insulin-producing cells. |
| 2216 | 16968152 | These cells differentiated into insulin-producing cells after addition of GLP-1. |
| 2217 | 16968152 | These nestin-positive cell-derived ICCs expressed numerous beta-cell lineage genes, including insulin; Glut-2; pancreatic duodenal homebox-1 protein (PDX-1); islet amyloid polypeptide (IAPP); neurogenin 3 (ngn3); and alpha, gamma, and delta cell gene markers. |
| 2218 | 16968152 | In addition, ICCs were characterized by coexpression of nestin/insulin and nestin/PDX-1. |
| 2219 | 16968152 | The levels of pancreas-related gene and protein expression and insulin secretion in the GLP-1 group were stronger than those in the normal controls. |
| 2220 | 16968152 | GLP-1 has been shown to be involved in stimulating the signaling pathways downstream of the transcription factor PDX-1, by increasing its protein and messenger RNA levels. |
| 2221 | 16968152 | We concluded that GLP-1 induced differentiation of nestin-positive progenitor embryonic stem cells into insulin-producing cells, which was achieved by upregulation of PDX-1 expression. |
| 2222 | 16968152 | Glucagon-like peptide-1 differentiation of primate embryonic stem cells into insulin-producing cells. |
| 2223 | 16968152 | The present study was performed to determine whether glucagon-like peptide-1 (GLP-1) stimulates differentiation of nestin-selected embryonic stem cells into insulin-producing cells. |
| 2224 | 16968152 | These cells differentiated into insulin-producing cells after addition of GLP-1. |
| 2225 | 16968152 | These nestin-positive cell-derived ICCs expressed numerous beta-cell lineage genes, including insulin; Glut-2; pancreatic duodenal homebox-1 protein (PDX-1); islet amyloid polypeptide (IAPP); neurogenin 3 (ngn3); and alpha, gamma, and delta cell gene markers. |
| 2226 | 16968152 | In addition, ICCs were characterized by coexpression of nestin/insulin and nestin/PDX-1. |
| 2227 | 16968152 | The levels of pancreas-related gene and protein expression and insulin secretion in the GLP-1 group were stronger than those in the normal controls. |
| 2228 | 16968152 | GLP-1 has been shown to be involved in stimulating the signaling pathways downstream of the transcription factor PDX-1, by increasing its protein and messenger RNA levels. |
| 2229 | 16968152 | We concluded that GLP-1 induced differentiation of nestin-positive progenitor embryonic stem cells into insulin-producing cells, which was achieved by upregulation of PDX-1 expression. |
| 2230 | 16968152 | Glucagon-like peptide-1 differentiation of primate embryonic stem cells into insulin-producing cells. |
| 2231 | 16968152 | The present study was performed to determine whether glucagon-like peptide-1 (GLP-1) stimulates differentiation of nestin-selected embryonic stem cells into insulin-producing cells. |
| 2232 | 16968152 | These cells differentiated into insulin-producing cells after addition of GLP-1. |
| 2233 | 16968152 | These nestin-positive cell-derived ICCs expressed numerous beta-cell lineage genes, including insulin; Glut-2; pancreatic duodenal homebox-1 protein (PDX-1); islet amyloid polypeptide (IAPP); neurogenin 3 (ngn3); and alpha, gamma, and delta cell gene markers. |
| 2234 | 16968152 | In addition, ICCs were characterized by coexpression of nestin/insulin and nestin/PDX-1. |
| 2235 | 16968152 | The levels of pancreas-related gene and protein expression and insulin secretion in the GLP-1 group were stronger than those in the normal controls. |
| 2236 | 16968152 | GLP-1 has been shown to be involved in stimulating the signaling pathways downstream of the transcription factor PDX-1, by increasing its protein and messenger RNA levels. |
| 2237 | 16968152 | We concluded that GLP-1 induced differentiation of nestin-positive progenitor embryonic stem cells into insulin-producing cells, which was achieved by upregulation of PDX-1 expression. |
| 2238 | 16968152 | Glucagon-like peptide-1 differentiation of primate embryonic stem cells into insulin-producing cells. |
| 2239 | 16968152 | The present study was performed to determine whether glucagon-like peptide-1 (GLP-1) stimulates differentiation of nestin-selected embryonic stem cells into insulin-producing cells. |
| 2240 | 16968152 | These cells differentiated into insulin-producing cells after addition of GLP-1. |
| 2241 | 16968152 | These nestin-positive cell-derived ICCs expressed numerous beta-cell lineage genes, including insulin; Glut-2; pancreatic duodenal homebox-1 protein (PDX-1); islet amyloid polypeptide (IAPP); neurogenin 3 (ngn3); and alpha, gamma, and delta cell gene markers. |
| 2242 | 16968152 | In addition, ICCs were characterized by coexpression of nestin/insulin and nestin/PDX-1. |
| 2243 | 16968152 | The levels of pancreas-related gene and protein expression and insulin secretion in the GLP-1 group were stronger than those in the normal controls. |
| 2244 | 16968152 | GLP-1 has been shown to be involved in stimulating the signaling pathways downstream of the transcription factor PDX-1, by increasing its protein and messenger RNA levels. |
| 2245 | 16968152 | We concluded that GLP-1 induced differentiation of nestin-positive progenitor embryonic stem cells into insulin-producing cells, which was achieved by upregulation of PDX-1 expression. |
| 2246 | 16990588 | The islet-like clusters showed endocrine gene expression typical for pancreatic beta-cell development and function, such as insulin (I and II), glucagon, somatostatin, GLUT-2, pancreatic duodenal homeobox-1 (PDX-1), and Pax 4. |
| 2247 | 17003335 | Fas, a death receptor regulated by IL-1beta, is involved in glucose-induced beta-cell apoptosis. |
| 2248 | 17003335 | Fas engagement can be switched from death signal to induction of proliferation when the caspase 8 inhibitor, FLICE-inhibitory protein (FLIP), is active. |
| 2249 | 17003335 | A similarly bimodal induction of FLIP, pancreatic duodenal homeobox (PDX)-1, and Pax4 mRNA expression, as well as glucose-stimulated insulin secretion, was observed. |
| 2250 | 17003335 | In contrast, Fas induction by IL-1beta was monophasic. |
| 2251 | 17003335 | Low IL-1beta also induced the IL-1 receptor antagonist (IL-1Ra), suppression of which by RNA interference abrogated the beneficial effects of low IL-1beta. |
| 2252 | 17003335 | Consistent with our in vitro results, IL-1beta knockout mice displayed glucose intolerance along with a decrease in islet Fas, FLIP, Pax4, and PDX-1 transcripts. |
| 2253 | 17003335 | These findings indicate that low IL-1beta levels positively influence beta-cell function and turnover through the Fas-FLIP pathway and that IL-1Ra production prevents harmful effects of high IL-1beta concentrations. |
| 2254 | 17003335 | Fas, a death receptor regulated by IL-1beta, is involved in glucose-induced beta-cell apoptosis. |
| 2255 | 17003335 | Fas engagement can be switched from death signal to induction of proliferation when the caspase 8 inhibitor, FLICE-inhibitory protein (FLIP), is active. |
| 2256 | 17003335 | A similarly bimodal induction of FLIP, pancreatic duodenal homeobox (PDX)-1, and Pax4 mRNA expression, as well as glucose-stimulated insulin secretion, was observed. |
| 2257 | 17003335 | In contrast, Fas induction by IL-1beta was monophasic. |
| 2258 | 17003335 | Low IL-1beta also induced the IL-1 receptor antagonist (IL-1Ra), suppression of which by RNA interference abrogated the beneficial effects of low IL-1beta. |
| 2259 | 17003335 | Consistent with our in vitro results, IL-1beta knockout mice displayed glucose intolerance along with a decrease in islet Fas, FLIP, Pax4, and PDX-1 transcripts. |
| 2260 | 17003335 | These findings indicate that low IL-1beta levels positively influence beta-cell function and turnover through the Fas-FLIP pathway and that IL-1Ra production prevents harmful effects of high IL-1beta concentrations. |
| 2261 | 17003479 | We demonstrate that under these experimental conditions the exocrine acinar cells lose their differentiated characteristics: expression of the acinar transcription factors p48/Ptf1alpha and Mist1 is decreased or lost, whereas expression of the embryonic transcription factor Pdx1 is increased. |
| 2262 | 17003479 | The receptors Notch1 and Notch2, members of the DSL family of Notch ligands, and the target genes in the Notch-signaling pathway Hes1, Hey1, and Hey2 become strongly up-regulated. |
| 2263 | 17003479 | This effect seems to be Hes1-independent and mainly coincides with decreased Hey1 and Hey2 mRNA expression. |
| 2264 | 17009890 | PPlike cells show a strong upregulation of Ipf1/Pdx1, p48, Isl-1 and Nkx6.1, but not Ngn3, NeuroD/ Beta2 or Pax4. |
| 2265 | 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. |
| 2266 | 17048266 | Forced expression of the beta-cell-specific transcription factor Pdx1 in hepatocytes also holds promise as a therapeutic strategy to increase insulin levels in diabetic individuals. |
| 2267 | 17049056 | Insulin secretion decreased on POD 3 in association with a significant increase of HIF-1alpha-related beta-cell death, which can be suppressed by short-term hyperbaric oxygen therapy. |
| 2268 | 17049056 | In contrast, improvement of nerve growth factor and duodenal homeobox factor-1 (PDx-1) production resulted in islet graft recovery and remodeling. |
| 2269 | 17049056 | In addition, significant activation of vascular endothelial growth factor in islet grafts on POD 7 correlated with development of massive newly formed microvessels, whose maturation is advanced on POD 14 with gradual diminution of HIF-1alpha. |
| 2270 | 17049056 | We conclude that (1) transplanted islets strongly express HIF-1alpha in association with beta-cell death and decreased insulin production until adequate revascularization is established and (2) early suppression of HIF-1alpha results in less beta-cell death thereby minimizing early graft failure. |
| 2271 | 17088535 | Rare islets contained human cells that colabeled for human insulin or PDX-1. |
| 2272 | 17095531 | It has been shown that abnormal O-GlcNAc modification (O-GlcNAcylation) of proteins is one of the causes of insulin resistance and diabetic complications. |
| 2273 | 17095531 | In this study, in order to examine the relationship between O-GlcNAcylation of proteins and glucose-stimulated insulin secretion in noninsulin-dependent type (type 2) diabetes, we investigated the level of O-GlcNAcylation of proteins, especially that of PDX-1, and the expression of O-GlcNAc transferase in Goto-Kakizaki (GK) rats, which are an animal model of type-2 diabetes. |
| 2274 | 17095531 | PUGNAc, an inhibitor of O-GlcNAcase, induced an elevation of O-GlcNAc level and a decrease of glucose-stimulated insulin secretion in isolated islets. |
| 2275 | 17095531 | These results indicate that elevation of the O-GlcNAcylation of proteins leads to deterioration of insulin secretion in the pancreas of diabetic GK rats, further providing evidence for the role of O-GlcNAc in the insulin secretion. |
| 2276 | 17110468 | Islet-derived fibroblast-like cells are not derived via epithelial-mesenchymal transition from Pdx-1 or insulin-positive cells. |
| 2277 | 17126328 | Two conserved domains in PCIF1 mediate interaction with pancreatic transcription factor PDX-1. |
| 2278 | 17126328 | PCIF1 is a TRAF and POZ domain containing nuclear factor that interacts with and inhibits transactivation of pancreatic homeodomain transcription factor PDX-1. |
| 2279 | 17126328 | Here, we demonstrate interaction of endogenous PDX-1 and PCIF1 in MIN6 insulinoma cells. |
| 2280 | 17126328 | Within PCIF1, the TRAF and POZ domains are both required for physical and functional interaction with the C-terminus of PDX-1, whereas the C-terminal domain of PCIF1 directs its nuclear localization. |
| 2281 | 17126328 | A human PDX-1 mutation associated with diabetes, E224K, disrupts the ability of PCIF1 to inhibit PDX-1 transactivation, suggesting that the interaction between PDX-1 and PCIF1 is required for normal glucose homeostasis. |
| 2282 | 17126328 | Understanding the functional roles of PCIF1 domains may have application to therapeutic beta-cell replacement strategies involving PDX-1 for the treatment of diabetes. |
| 2283 | 17126328 | Two conserved domains in PCIF1 mediate interaction with pancreatic transcription factor PDX-1. |
| 2284 | 17126328 | PCIF1 is a TRAF and POZ domain containing nuclear factor that interacts with and inhibits transactivation of pancreatic homeodomain transcription factor PDX-1. |
| 2285 | 17126328 | Here, we demonstrate interaction of endogenous PDX-1 and PCIF1 in MIN6 insulinoma cells. |
| 2286 | 17126328 | Within PCIF1, the TRAF and POZ domains are both required for physical and functional interaction with the C-terminus of PDX-1, whereas the C-terminal domain of PCIF1 directs its nuclear localization. |
| 2287 | 17126328 | A human PDX-1 mutation associated with diabetes, E224K, disrupts the ability of PCIF1 to inhibit PDX-1 transactivation, suggesting that the interaction between PDX-1 and PCIF1 is required for normal glucose homeostasis. |
| 2288 | 17126328 | Understanding the functional roles of PCIF1 domains may have application to therapeutic beta-cell replacement strategies involving PDX-1 for the treatment of diabetes. |
| 2289 | 17126328 | Two conserved domains in PCIF1 mediate interaction with pancreatic transcription factor PDX-1. |
| 2290 | 17126328 | PCIF1 is a TRAF and POZ domain containing nuclear factor that interacts with and inhibits transactivation of pancreatic homeodomain transcription factor PDX-1. |
| 2291 | 17126328 | Here, we demonstrate interaction of endogenous PDX-1 and PCIF1 in MIN6 insulinoma cells. |
| 2292 | 17126328 | Within PCIF1, the TRAF and POZ domains are both required for physical and functional interaction with the C-terminus of PDX-1, whereas the C-terminal domain of PCIF1 directs its nuclear localization. |
| 2293 | 17126328 | A human PDX-1 mutation associated with diabetes, E224K, disrupts the ability of PCIF1 to inhibit PDX-1 transactivation, suggesting that the interaction between PDX-1 and PCIF1 is required for normal glucose homeostasis. |
| 2294 | 17126328 | Understanding the functional roles of PCIF1 domains may have application to therapeutic beta-cell replacement strategies involving PDX-1 for the treatment of diabetes. |
| 2295 | 17126328 | Two conserved domains in PCIF1 mediate interaction with pancreatic transcription factor PDX-1. |
| 2296 | 17126328 | PCIF1 is a TRAF and POZ domain containing nuclear factor that interacts with and inhibits transactivation of pancreatic homeodomain transcription factor PDX-1. |
| 2297 | 17126328 | Here, we demonstrate interaction of endogenous PDX-1 and PCIF1 in MIN6 insulinoma cells. |
| 2298 | 17126328 | Within PCIF1, the TRAF and POZ domains are both required for physical and functional interaction with the C-terminus of PDX-1, whereas the C-terminal domain of PCIF1 directs its nuclear localization. |
| 2299 | 17126328 | A human PDX-1 mutation associated with diabetes, E224K, disrupts the ability of PCIF1 to inhibit PDX-1 transactivation, suggesting that the interaction between PDX-1 and PCIF1 is required for normal glucose homeostasis. |
| 2300 | 17126328 | Understanding the functional roles of PCIF1 domains may have application to therapeutic beta-cell replacement strategies involving PDX-1 for the treatment of diabetes. |
| 2301 | 17126328 | Two conserved domains in PCIF1 mediate interaction with pancreatic transcription factor PDX-1. |
| 2302 | 17126328 | PCIF1 is a TRAF and POZ domain containing nuclear factor that interacts with and inhibits transactivation of pancreatic homeodomain transcription factor PDX-1. |
| 2303 | 17126328 | Here, we demonstrate interaction of endogenous PDX-1 and PCIF1 in MIN6 insulinoma cells. |
| 2304 | 17126328 | Within PCIF1, the TRAF and POZ domains are both required for physical and functional interaction with the C-terminus of PDX-1, whereas the C-terminal domain of PCIF1 directs its nuclear localization. |
| 2305 | 17126328 | A human PDX-1 mutation associated with diabetes, E224K, disrupts the ability of PCIF1 to inhibit PDX-1 transactivation, suggesting that the interaction between PDX-1 and PCIF1 is required for normal glucose homeostasis. |
| 2306 | 17126328 | Understanding the functional roles of PCIF1 domains may have application to therapeutic beta-cell replacement strategies involving PDX-1 for the treatment of diabetes. |
| 2307 | 17126328 | Two conserved domains in PCIF1 mediate interaction with pancreatic transcription factor PDX-1. |
| 2308 | 17126328 | PCIF1 is a TRAF and POZ domain containing nuclear factor that interacts with and inhibits transactivation of pancreatic homeodomain transcription factor PDX-1. |
| 2309 | 17126328 | Here, we demonstrate interaction of endogenous PDX-1 and PCIF1 in MIN6 insulinoma cells. |
| 2310 | 17126328 | Within PCIF1, the TRAF and POZ domains are both required for physical and functional interaction with the C-terminus of PDX-1, whereas the C-terminal domain of PCIF1 directs its nuclear localization. |
| 2311 | 17126328 | A human PDX-1 mutation associated with diabetes, E224K, disrupts the ability of PCIF1 to inhibit PDX-1 transactivation, suggesting that the interaction between PDX-1 and PCIF1 is required for normal glucose homeostasis. |
| 2312 | 17126328 | Understanding the functional roles of PCIF1 domains may have application to therapeutic beta-cell replacement strategies involving PDX-1 for the treatment of diabetes. |
| 2313 | 17130462 | The major findings are that the A-box sites that bind PDX-1 are among the most highly conserved regulatory sequences, and that the conservation of the C1, E1, and CRE sequences emphasize the importance of MafA, E47/beta2, and cAMP-associated regulation. |
| 2314 | 17130469 | Transgenic mice in which Hnf6 expression is maintained in postnatal islets (pdx1(PB)Hnf6) show overt diabetes and impaired glucose-stimulated insulin secretion (GSIS) at weaning. |
| 2315 | 17130469 | We provide evidence that continued expression of Hnf6 impairs GSIS by altering insulin granule biosynthesis, resulting in a reduced response to secretagogues. |
| 2316 | 17130469 | Sustained expression of Hnf6 also results in downregulation of the beta-cell-specific transcription factor MafA and a decrease in total pancreatic insulin. |
| 2317 | 17130472 | We found insulin receptor substrate (IRS)2 and enhanced-activated Akt immunoreactivity in islets and ducts that correlated with increased pancreatic duodenal homeobox (PDX)1 expression. |
| 2318 | 17130472 | In contrast, forkhead box O1 expression was decreased in islets but increased in ducts, suggesting distinct PDX1 regulatory mechanisms in these tissues. |
| 2319 | 17130472 | We found insulin receptor substrate (IRS)2 and enhanced-activated Akt immunoreactivity in islets and ducts that correlated with increased pancreatic duodenal homeobox (PDX)1 expression. |
| 2320 | 17130472 | In contrast, forkhead box O1 expression was decreased in islets but increased in ducts, suggesting distinct PDX1 regulatory mechanisms in these tissues. |
| 2321 | 17141044 | During differentiation, transcript levels of pancreas-specific transcription factors (i.e., Pdx1, Pax4) and of genes specific for early and mature beta cells, including insulin, islet amyloid pancreatic peptide, somatostatin, and glucagon, are upregulated. |
| 2322 | 17150967 | Regulation of pancreas duodenum homeobox-1 expression by early growth response-1. |
| 2323 | 17150967 | The homeodomain transcription factor pancreas duodenum homeobox-1 (PDX-1) is a key regulator of pancreatic beta-cell development, function, and survival. |
| 2324 | 17150967 | Deficits in PDX-1 expression result in insulin deficiency and hyperglycemia. |
| 2325 | 17150967 | We previously found that the glucose-responsive transcription factor early growth response-1 (Egr-1) activates the insulin promoter in part by increasing expression levels of PDX-1. |
| 2326 | 17150967 | We now report that Egr-1 binds and activates multiple regulatory sites within the pdx-1 promoter. |
| 2327 | 17150967 | We identified consensus Egr-1 recognition sequences within proximal and distal regions of the mouse pdx-1 promoter and demonstrated specific binding of Egr-1 by chromatin immunoprecipitation and electrophoretic mobility shift assays. |
| 2328 | 17150967 | Overexpression of Egr-1 increased transcriptional activation of the -4500 proximal pdx-1 promoter and of the highly conserved regulatory Areas I, II, and III. |
| 2329 | 17150967 | Egr-1 increased the transcriptional activation of Areas I and II, despite the absence of Egr-1 recognition sequences within this promoter segment, suggesting that Egr-1 also can regulate the pdx-1 promoter indirectly. |
| 2330 | 17150967 | Egr-1 increased, and a dominant-negative Egr-1 mutant repressed, the transcriptional activation of distal pdx-1 promoter sequences. |
| 2331 | 17150967 | Our data indicate that Egr-1 regulates expression of PDX-1 in pancreatic beta-cells by both direct and indirect activation of the pdx-1 promoter. |
| 2332 | 17150967 | We propose that Egr-1 expression levels may act as a sensor in pancreatic beta-cells to translate extracellular signals into changes in PDX-1 expression levels and pancreatic beta-cell function. |
| 2333 | 17150967 | Regulation of pancreas duodenum homeobox-1 expression by early growth response-1. |
| 2334 | 17150967 | The homeodomain transcription factor pancreas duodenum homeobox-1 (PDX-1) is a key regulator of pancreatic beta-cell development, function, and survival. |
| 2335 | 17150967 | Deficits in PDX-1 expression result in insulin deficiency and hyperglycemia. |
| 2336 | 17150967 | We previously found that the glucose-responsive transcription factor early growth response-1 (Egr-1) activates the insulin promoter in part by increasing expression levels of PDX-1. |
| 2337 | 17150967 | We now report that Egr-1 binds and activates multiple regulatory sites within the pdx-1 promoter. |
| 2338 | 17150967 | We identified consensus Egr-1 recognition sequences within proximal and distal regions of the mouse pdx-1 promoter and demonstrated specific binding of Egr-1 by chromatin immunoprecipitation and electrophoretic mobility shift assays. |
| 2339 | 17150967 | Overexpression of Egr-1 increased transcriptional activation of the -4500 proximal pdx-1 promoter and of the highly conserved regulatory Areas I, II, and III. |
| 2340 | 17150967 | Egr-1 increased the transcriptional activation of Areas I and II, despite the absence of Egr-1 recognition sequences within this promoter segment, suggesting that Egr-1 also can regulate the pdx-1 promoter indirectly. |
| 2341 | 17150967 | Egr-1 increased, and a dominant-negative Egr-1 mutant repressed, the transcriptional activation of distal pdx-1 promoter sequences. |
| 2342 | 17150967 | Our data indicate that Egr-1 regulates expression of PDX-1 in pancreatic beta-cells by both direct and indirect activation of the pdx-1 promoter. |
| 2343 | 17150967 | We propose that Egr-1 expression levels may act as a sensor in pancreatic beta-cells to translate extracellular signals into changes in PDX-1 expression levels and pancreatic beta-cell function. |
| 2344 | 17150967 | Regulation of pancreas duodenum homeobox-1 expression by early growth response-1. |
| 2345 | 17150967 | The homeodomain transcription factor pancreas duodenum homeobox-1 (PDX-1) is a key regulator of pancreatic beta-cell development, function, and survival. |
| 2346 | 17150967 | Deficits in PDX-1 expression result in insulin deficiency and hyperglycemia. |
| 2347 | 17150967 | We previously found that the glucose-responsive transcription factor early growth response-1 (Egr-1) activates the insulin promoter in part by increasing expression levels of PDX-1. |
| 2348 | 17150967 | We now report that Egr-1 binds and activates multiple regulatory sites within the pdx-1 promoter. |
| 2349 | 17150967 | We identified consensus Egr-1 recognition sequences within proximal and distal regions of the mouse pdx-1 promoter and demonstrated specific binding of Egr-1 by chromatin immunoprecipitation and electrophoretic mobility shift assays. |
| 2350 | 17150967 | Overexpression of Egr-1 increased transcriptional activation of the -4500 proximal pdx-1 promoter and of the highly conserved regulatory Areas I, II, and III. |
| 2351 | 17150967 | Egr-1 increased the transcriptional activation of Areas I and II, despite the absence of Egr-1 recognition sequences within this promoter segment, suggesting that Egr-1 also can regulate the pdx-1 promoter indirectly. |
| 2352 | 17150967 | Egr-1 increased, and a dominant-negative Egr-1 mutant repressed, the transcriptional activation of distal pdx-1 promoter sequences. |
| 2353 | 17150967 | Our data indicate that Egr-1 regulates expression of PDX-1 in pancreatic beta-cells by both direct and indirect activation of the pdx-1 promoter. |
| 2354 | 17150967 | We propose that Egr-1 expression levels may act as a sensor in pancreatic beta-cells to translate extracellular signals into changes in PDX-1 expression levels and pancreatic beta-cell function. |
| 2355 | 17150967 | Regulation of pancreas duodenum homeobox-1 expression by early growth response-1. |
| 2356 | 17150967 | The homeodomain transcription factor pancreas duodenum homeobox-1 (PDX-1) is a key regulator of pancreatic beta-cell development, function, and survival. |
| 2357 | 17150967 | Deficits in PDX-1 expression result in insulin deficiency and hyperglycemia. |
| 2358 | 17150967 | We previously found that the glucose-responsive transcription factor early growth response-1 (Egr-1) activates the insulin promoter in part by increasing expression levels of PDX-1. |
| 2359 | 17150967 | We now report that Egr-1 binds and activates multiple regulatory sites within the pdx-1 promoter. |
| 2360 | 17150967 | We identified consensus Egr-1 recognition sequences within proximal and distal regions of the mouse pdx-1 promoter and demonstrated specific binding of Egr-1 by chromatin immunoprecipitation and electrophoretic mobility shift assays. |
| 2361 | 17150967 | Overexpression of Egr-1 increased transcriptional activation of the -4500 proximal pdx-1 promoter and of the highly conserved regulatory Areas I, II, and III. |
| 2362 | 17150967 | Egr-1 increased the transcriptional activation of Areas I and II, despite the absence of Egr-1 recognition sequences within this promoter segment, suggesting that Egr-1 also can regulate the pdx-1 promoter indirectly. |
| 2363 | 17150967 | Egr-1 increased, and a dominant-negative Egr-1 mutant repressed, the transcriptional activation of distal pdx-1 promoter sequences. |
| 2364 | 17150967 | Our data indicate that Egr-1 regulates expression of PDX-1 in pancreatic beta-cells by both direct and indirect activation of the pdx-1 promoter. |
| 2365 | 17150967 | We propose that Egr-1 expression levels may act as a sensor in pancreatic beta-cells to translate extracellular signals into changes in PDX-1 expression levels and pancreatic beta-cell function. |
| 2366 | 17150967 | Regulation of pancreas duodenum homeobox-1 expression by early growth response-1. |
| 2367 | 17150967 | The homeodomain transcription factor pancreas duodenum homeobox-1 (PDX-1) is a key regulator of pancreatic beta-cell development, function, and survival. |
| 2368 | 17150967 | Deficits in PDX-1 expression result in insulin deficiency and hyperglycemia. |
| 2369 | 17150967 | We previously found that the glucose-responsive transcription factor early growth response-1 (Egr-1) activates the insulin promoter in part by increasing expression levels of PDX-1. |
| 2370 | 17150967 | We now report that Egr-1 binds and activates multiple regulatory sites within the pdx-1 promoter. |
| 2371 | 17150967 | We identified consensus Egr-1 recognition sequences within proximal and distal regions of the mouse pdx-1 promoter and demonstrated specific binding of Egr-1 by chromatin immunoprecipitation and electrophoretic mobility shift assays. |
| 2372 | 17150967 | Overexpression of Egr-1 increased transcriptional activation of the -4500 proximal pdx-1 promoter and of the highly conserved regulatory Areas I, II, and III. |
| 2373 | 17150967 | Egr-1 increased the transcriptional activation of Areas I and II, despite the absence of Egr-1 recognition sequences within this promoter segment, suggesting that Egr-1 also can regulate the pdx-1 promoter indirectly. |
| 2374 | 17150967 | Egr-1 increased, and a dominant-negative Egr-1 mutant repressed, the transcriptional activation of distal pdx-1 promoter sequences. |
| 2375 | 17150967 | Our data indicate that Egr-1 regulates expression of PDX-1 in pancreatic beta-cells by both direct and indirect activation of the pdx-1 promoter. |
| 2376 | 17150967 | We propose that Egr-1 expression levels may act as a sensor in pancreatic beta-cells to translate extracellular signals into changes in PDX-1 expression levels and pancreatic beta-cell function. |
| 2377 | 17150967 | Regulation of pancreas duodenum homeobox-1 expression by early growth response-1. |
| 2378 | 17150967 | The homeodomain transcription factor pancreas duodenum homeobox-1 (PDX-1) is a key regulator of pancreatic beta-cell development, function, and survival. |
| 2379 | 17150967 | Deficits in PDX-1 expression result in insulin deficiency and hyperglycemia. |
| 2380 | 17150967 | We previously found that the glucose-responsive transcription factor early growth response-1 (Egr-1) activates the insulin promoter in part by increasing expression levels of PDX-1. |
| 2381 | 17150967 | We now report that Egr-1 binds and activates multiple regulatory sites within the pdx-1 promoter. |
| 2382 | 17150967 | We identified consensus Egr-1 recognition sequences within proximal and distal regions of the mouse pdx-1 promoter and demonstrated specific binding of Egr-1 by chromatin immunoprecipitation and electrophoretic mobility shift assays. |
| 2383 | 17150967 | Overexpression of Egr-1 increased transcriptional activation of the -4500 proximal pdx-1 promoter and of the highly conserved regulatory Areas I, II, and III. |
| 2384 | 17150967 | Egr-1 increased the transcriptional activation of Areas I and II, despite the absence of Egr-1 recognition sequences within this promoter segment, suggesting that Egr-1 also can regulate the pdx-1 promoter indirectly. |
| 2385 | 17150967 | Egr-1 increased, and a dominant-negative Egr-1 mutant repressed, the transcriptional activation of distal pdx-1 promoter sequences. |
| 2386 | 17150967 | Our data indicate that Egr-1 regulates expression of PDX-1 in pancreatic beta-cells by both direct and indirect activation of the pdx-1 promoter. |
| 2387 | 17150967 | We propose that Egr-1 expression levels may act as a sensor in pancreatic beta-cells to translate extracellular signals into changes in PDX-1 expression levels and pancreatic beta-cell function. |
| 2388 | 17150967 | Regulation of pancreas duodenum homeobox-1 expression by early growth response-1. |
| 2389 | 17150967 | The homeodomain transcription factor pancreas duodenum homeobox-1 (PDX-1) is a key regulator of pancreatic beta-cell development, function, and survival. |
| 2390 | 17150967 | Deficits in PDX-1 expression result in insulin deficiency and hyperglycemia. |
| 2391 | 17150967 | We previously found that the glucose-responsive transcription factor early growth response-1 (Egr-1) activates the insulin promoter in part by increasing expression levels of PDX-1. |
| 2392 | 17150967 | We now report that Egr-1 binds and activates multiple regulatory sites within the pdx-1 promoter. |
| 2393 | 17150967 | We identified consensus Egr-1 recognition sequences within proximal and distal regions of the mouse pdx-1 promoter and demonstrated specific binding of Egr-1 by chromatin immunoprecipitation and electrophoretic mobility shift assays. |
| 2394 | 17150967 | Overexpression of Egr-1 increased transcriptional activation of the -4500 proximal pdx-1 promoter and of the highly conserved regulatory Areas I, II, and III. |
| 2395 | 17150967 | Egr-1 increased the transcriptional activation of Areas I and II, despite the absence of Egr-1 recognition sequences within this promoter segment, suggesting that Egr-1 also can regulate the pdx-1 promoter indirectly. |
| 2396 | 17150967 | Egr-1 increased, and a dominant-negative Egr-1 mutant repressed, the transcriptional activation of distal pdx-1 promoter sequences. |
| 2397 | 17150967 | Our data indicate that Egr-1 regulates expression of PDX-1 in pancreatic beta-cells by both direct and indirect activation of the pdx-1 promoter. |
| 2398 | 17150967 | We propose that Egr-1 expression levels may act as a sensor in pancreatic beta-cells to translate extracellular signals into changes in PDX-1 expression levels and pancreatic beta-cell function. |
| 2399 | 17150967 | Regulation of pancreas duodenum homeobox-1 expression by early growth response-1. |
| 2400 | 17150967 | The homeodomain transcription factor pancreas duodenum homeobox-1 (PDX-1) is a key regulator of pancreatic beta-cell development, function, and survival. |
| 2401 | 17150967 | Deficits in PDX-1 expression result in insulin deficiency and hyperglycemia. |
| 2402 | 17150967 | We previously found that the glucose-responsive transcription factor early growth response-1 (Egr-1) activates the insulin promoter in part by increasing expression levels of PDX-1. |
| 2403 | 17150967 | We now report that Egr-1 binds and activates multiple regulatory sites within the pdx-1 promoter. |
| 2404 | 17150967 | We identified consensus Egr-1 recognition sequences within proximal and distal regions of the mouse pdx-1 promoter and demonstrated specific binding of Egr-1 by chromatin immunoprecipitation and electrophoretic mobility shift assays. |
| 2405 | 17150967 | Overexpression of Egr-1 increased transcriptional activation of the -4500 proximal pdx-1 promoter and of the highly conserved regulatory Areas I, II, and III. |
| 2406 | 17150967 | Egr-1 increased the transcriptional activation of Areas I and II, despite the absence of Egr-1 recognition sequences within this promoter segment, suggesting that Egr-1 also can regulate the pdx-1 promoter indirectly. |
| 2407 | 17150967 | Egr-1 increased, and a dominant-negative Egr-1 mutant repressed, the transcriptional activation of distal pdx-1 promoter sequences. |
| 2408 | 17150967 | Our data indicate that Egr-1 regulates expression of PDX-1 in pancreatic beta-cells by both direct and indirect activation of the pdx-1 promoter. |
| 2409 | 17150967 | We propose that Egr-1 expression levels may act as a sensor in pancreatic beta-cells to translate extracellular signals into changes in PDX-1 expression levels and pancreatic beta-cell function. |
| 2410 | 17150967 | Regulation of pancreas duodenum homeobox-1 expression by early growth response-1. |
| 2411 | 17150967 | The homeodomain transcription factor pancreas duodenum homeobox-1 (PDX-1) is a key regulator of pancreatic beta-cell development, function, and survival. |
| 2412 | 17150967 | Deficits in PDX-1 expression result in insulin deficiency and hyperglycemia. |
| 2413 | 17150967 | We previously found that the glucose-responsive transcription factor early growth response-1 (Egr-1) activates the insulin promoter in part by increasing expression levels of PDX-1. |
| 2414 | 17150967 | We now report that Egr-1 binds and activates multiple regulatory sites within the pdx-1 promoter. |
| 2415 | 17150967 | We identified consensus Egr-1 recognition sequences within proximal and distal regions of the mouse pdx-1 promoter and demonstrated specific binding of Egr-1 by chromatin immunoprecipitation and electrophoretic mobility shift assays. |
| 2416 | 17150967 | Overexpression of Egr-1 increased transcriptional activation of the -4500 proximal pdx-1 promoter and of the highly conserved regulatory Areas I, II, and III. |
| 2417 | 17150967 | Egr-1 increased the transcriptional activation of Areas I and II, despite the absence of Egr-1 recognition sequences within this promoter segment, suggesting that Egr-1 also can regulate the pdx-1 promoter indirectly. |
| 2418 | 17150967 | Egr-1 increased, and a dominant-negative Egr-1 mutant repressed, the transcriptional activation of distal pdx-1 promoter sequences. |
| 2419 | 17150967 | Our data indicate that Egr-1 regulates expression of PDX-1 in pancreatic beta-cells by both direct and indirect activation of the pdx-1 promoter. |
| 2420 | 17150967 | We propose that Egr-1 expression levels may act as a sensor in pancreatic beta-cells to translate extracellular signals into changes in PDX-1 expression levels and pancreatic beta-cell function. |
| 2421 | 17150967 | Regulation of pancreas duodenum homeobox-1 expression by early growth response-1. |
| 2422 | 17150967 | The homeodomain transcription factor pancreas duodenum homeobox-1 (PDX-1) is a key regulator of pancreatic beta-cell development, function, and survival. |
| 2423 | 17150967 | Deficits in PDX-1 expression result in insulin deficiency and hyperglycemia. |
| 2424 | 17150967 | We previously found that the glucose-responsive transcription factor early growth response-1 (Egr-1) activates the insulin promoter in part by increasing expression levels of PDX-1. |
| 2425 | 17150967 | We now report that Egr-1 binds and activates multiple regulatory sites within the pdx-1 promoter. |
| 2426 | 17150967 | We identified consensus Egr-1 recognition sequences within proximal and distal regions of the mouse pdx-1 promoter and demonstrated specific binding of Egr-1 by chromatin immunoprecipitation and electrophoretic mobility shift assays. |
| 2427 | 17150967 | Overexpression of Egr-1 increased transcriptional activation of the -4500 proximal pdx-1 promoter and of the highly conserved regulatory Areas I, II, and III. |
| 2428 | 17150967 | Egr-1 increased the transcriptional activation of Areas I and II, despite the absence of Egr-1 recognition sequences within this promoter segment, suggesting that Egr-1 also can regulate the pdx-1 promoter indirectly. |
| 2429 | 17150967 | Egr-1 increased, and a dominant-negative Egr-1 mutant repressed, the transcriptional activation of distal pdx-1 promoter sequences. |
| 2430 | 17150967 | Our data indicate that Egr-1 regulates expression of PDX-1 in pancreatic beta-cells by both direct and indirect activation of the pdx-1 promoter. |
| 2431 | 17150967 | We propose that Egr-1 expression levels may act as a sensor in pancreatic beta-cells to translate extracellular signals into changes in PDX-1 expression levels and pancreatic beta-cell function. |
| 2432 | 17158802 | Insulin protects islets from apoptosis via Pdx1 and specific changes in the human islet proteome. |
| 2433 | 17158802 | Insulin treatment was associated with the nuclear localization of Pdx1 and the prosurvival effects of insulin were largely absent in islets 50% deficient in Pdx1, providing direct evidence that Pdx1 is a signaling target of insulin. |
| 2434 | 17158802 | Physiological levels of insulin did not increase Akt phosphorylation, and the protective effects of insulin were only partially altered in islets lacking 80% of normal Akt activity, suggesting the presence of additional insulin-regulated antiapoptotic pathways. |
| 2435 | 17158802 | Bridge-1, a Pdx1-binding partner and regulator of beta-cell survival, was increased significantly at low insulin doses. |
| 2436 | 17158802 | Together, these data suggest that insulin can act as a master regulator of islet survival by regulating Pdx1. |
| 2437 | 17158802 | Insulin protects islets from apoptosis via Pdx1 and specific changes in the human islet proteome. |
| 2438 | 17158802 | Insulin treatment was associated with the nuclear localization of Pdx1 and the prosurvival effects of insulin were largely absent in islets 50% deficient in Pdx1, providing direct evidence that Pdx1 is a signaling target of insulin. |
| 2439 | 17158802 | Physiological levels of insulin did not increase Akt phosphorylation, and the protective effects of insulin were only partially altered in islets lacking 80% of normal Akt activity, suggesting the presence of additional insulin-regulated antiapoptotic pathways. |
| 2440 | 17158802 | Bridge-1, a Pdx1-binding partner and regulator of beta-cell survival, was increased significantly at low insulin doses. |
| 2441 | 17158802 | Together, these data suggest that insulin can act as a master regulator of islet survival by regulating Pdx1. |
| 2442 | 17158802 | Insulin protects islets from apoptosis via Pdx1 and specific changes in the human islet proteome. |
| 2443 | 17158802 | Insulin treatment was associated with the nuclear localization of Pdx1 and the prosurvival effects of insulin were largely absent in islets 50% deficient in Pdx1, providing direct evidence that Pdx1 is a signaling target of insulin. |
| 2444 | 17158802 | Physiological levels of insulin did not increase Akt phosphorylation, and the protective effects of insulin were only partially altered in islets lacking 80% of normal Akt activity, suggesting the presence of additional insulin-regulated antiapoptotic pathways. |
| 2445 | 17158802 | Bridge-1, a Pdx1-binding partner and regulator of beta-cell survival, was increased significantly at low insulin doses. |
| 2446 | 17158802 | Together, these data suggest that insulin can act as a master regulator of islet survival by regulating Pdx1. |
| 2447 | 17172056 | The proportion of insulin-producing cells differentiated from Pdx-1+BMSCs was 28.23% +/- 2.56%, higher than that from BMSCs transfected with vacant vector and Pdx-1-BMSCs (7.23% +/- 1.56% and 4.08% +/- 2.69% respectively) by flow cytometry. |
| 2448 | 17172056 | Immunocytochemical examination also testified the expression of multiple beta-cells-specific genes such as insulin, glucagons, somatostatin in differentiated BMSCs. |
| 2449 | 17172056 | Glucose-induced insulin secretion from Pdx-1+BMSCs in 5 mmol/L and 25 mmol/L glocuse was (56.61 +/- 4.82) microU/mL and (115.29 +/- 2.56) microU/mL respectively, which were much higher than those from Pdx-1-BMSCs ((25.53 +/- 6.49) microU/mL and (53.26 +/- 7.56) microU/mL respectively). |
| 2450 | 17172056 | The proportion of insulin-producing cells differentiated from Pdx-1+BMSCs was 28.23% +/- 2.56%, higher than that from BMSCs transfected with vacant vector and Pdx-1-BMSCs (7.23% +/- 1.56% and 4.08% +/- 2.69% respectively) by flow cytometry. |
| 2451 | 17172056 | Immunocytochemical examination also testified the expression of multiple beta-cells-specific genes such as insulin, glucagons, somatostatin in differentiated BMSCs. |
| 2452 | 17172056 | Glucose-induced insulin secretion from Pdx-1+BMSCs in 5 mmol/L and 25 mmol/L glocuse was (56.61 +/- 4.82) microU/mL and (115.29 +/- 2.56) microU/mL respectively, which were much higher than those from Pdx-1-BMSCs ((25.53 +/- 6.49) microU/mL and (53.26 +/- 7.56) microU/mL respectively). |
| 2453 | 17185798 | In addition, we demonstrate the presence of cells co-expressing PYY and the critical pancreatic transcription factor pancreatic duodenal homeobox1 (PDX-1). |
| 2454 | 17185798 | Furthermore, we have found that PYY can act in concert with IGF-1 to stimulate cellular responsiveness in pancreatic epithelial cells in vitro. |
| 2455 | 17192469 | Peroxisome proliferator-activated receptor-gamma regulates expression of PDX-1 and NKX6.1 in INS-1 cells. |
| 2456 | 17192469 | We studied isolated islets and pancreas sections from 14-day post-Px versus sham-operated rats and observed a doubling of beta-cell nuclear peroxisome proliferator-activated receptor (PPAR)-gamma protein, along with a 2-fold increase in nuclear pancreatic duodenal homeobox (Pdx)-1 protein and a 1.4-fold increase in beta-cell nuclear Nkx6.1 immunostaining. |
| 2457 | 17192469 | A 3-day incubation with the PPAR-gamma agonist troglitazone reduced proliferation and increased Pdx-1 and Nkx6.1 immunostaining, along with glucokinase and GLUT2. |
| 2458 | 17192469 | Also, a 75% knockdown of PPAR-gamma using RNA interference lowered the mRNA levels of Pdx-1, glucokinase, GLUT2, and proinsulin II by more than half. |
| 2459 | 17192469 | Our results show a dual effect of PPAR-gamma in INS-1 cells: to curtail proliferation and promote maturation, the latter via enhanced expression of Pdx-1 and Nkx6.1. |
| 2460 | 17192469 | Peroxisome proliferator-activated receptor-gamma regulates expression of PDX-1 and NKX6.1 in INS-1 cells. |
| 2461 | 17192469 | We studied isolated islets and pancreas sections from 14-day post-Px versus sham-operated rats and observed a doubling of beta-cell nuclear peroxisome proliferator-activated receptor (PPAR)-gamma protein, along with a 2-fold increase in nuclear pancreatic duodenal homeobox (Pdx)-1 protein and a 1.4-fold increase in beta-cell nuclear Nkx6.1 immunostaining. |
| 2462 | 17192469 | A 3-day incubation with the PPAR-gamma agonist troglitazone reduced proliferation and increased Pdx-1 and Nkx6.1 immunostaining, along with glucokinase and GLUT2. |
| 2463 | 17192469 | Also, a 75% knockdown of PPAR-gamma using RNA interference lowered the mRNA levels of Pdx-1, glucokinase, GLUT2, and proinsulin II by more than half. |
| 2464 | 17192469 | Our results show a dual effect of PPAR-gamma in INS-1 cells: to curtail proliferation and promote maturation, the latter via enhanced expression of Pdx-1 and Nkx6.1. |
| 2465 | 17192469 | Peroxisome proliferator-activated receptor-gamma regulates expression of PDX-1 and NKX6.1 in INS-1 cells. |
| 2466 | 17192469 | We studied isolated islets and pancreas sections from 14-day post-Px versus sham-operated rats and observed a doubling of beta-cell nuclear peroxisome proliferator-activated receptor (PPAR)-gamma protein, along with a 2-fold increase in nuclear pancreatic duodenal homeobox (Pdx)-1 protein and a 1.4-fold increase in beta-cell nuclear Nkx6.1 immunostaining. |
| 2467 | 17192469 | A 3-day incubation with the PPAR-gamma agonist troglitazone reduced proliferation and increased Pdx-1 and Nkx6.1 immunostaining, along with glucokinase and GLUT2. |
| 2468 | 17192469 | Also, a 75% knockdown of PPAR-gamma using RNA interference lowered the mRNA levels of Pdx-1, glucokinase, GLUT2, and proinsulin II by more than half. |
| 2469 | 17192469 | Our results show a dual effect of PPAR-gamma in INS-1 cells: to curtail proliferation and promote maturation, the latter via enhanced expression of Pdx-1 and Nkx6.1. |
| 2470 | 17192469 | Peroxisome proliferator-activated receptor-gamma regulates expression of PDX-1 and NKX6.1 in INS-1 cells. |
| 2471 | 17192469 | We studied isolated islets and pancreas sections from 14-day post-Px versus sham-operated rats and observed a doubling of beta-cell nuclear peroxisome proliferator-activated receptor (PPAR)-gamma protein, along with a 2-fold increase in nuclear pancreatic duodenal homeobox (Pdx)-1 protein and a 1.4-fold increase in beta-cell nuclear Nkx6.1 immunostaining. |
| 2472 | 17192469 | A 3-day incubation with the PPAR-gamma agonist troglitazone reduced proliferation and increased Pdx-1 and Nkx6.1 immunostaining, along with glucokinase and GLUT2. |
| 2473 | 17192469 | Also, a 75% knockdown of PPAR-gamma using RNA interference lowered the mRNA levels of Pdx-1, glucokinase, GLUT2, and proinsulin II by more than half. |
| 2474 | 17192469 | Our results show a dual effect of PPAR-gamma in INS-1 cells: to curtail proliferation and promote maturation, the latter via enhanced expression of Pdx-1 and Nkx6.1. |
| 2475 | 17192469 | Peroxisome proliferator-activated receptor-gamma regulates expression of PDX-1 and NKX6.1 in INS-1 cells. |
| 2476 | 17192469 | We studied isolated islets and pancreas sections from 14-day post-Px versus sham-operated rats and observed a doubling of beta-cell nuclear peroxisome proliferator-activated receptor (PPAR)-gamma protein, along with a 2-fold increase in nuclear pancreatic duodenal homeobox (Pdx)-1 protein and a 1.4-fold increase in beta-cell nuclear Nkx6.1 immunostaining. |
| 2477 | 17192469 | A 3-day incubation with the PPAR-gamma agonist troglitazone reduced proliferation and increased Pdx-1 and Nkx6.1 immunostaining, along with glucokinase and GLUT2. |
| 2478 | 17192469 | Also, a 75% knockdown of PPAR-gamma using RNA interference lowered the mRNA levels of Pdx-1, glucokinase, GLUT2, and proinsulin II by more than half. |
| 2479 | 17192469 | Our results show a dual effect of PPAR-gamma in INS-1 cells: to curtail proliferation and promote maturation, the latter via enhanced expression of Pdx-1 and Nkx6.1. |
| 2480 | 17226789 | Generation of insulin-producing cells from PDX-1 gene-modified human mesenchymal stem cells. |
| 2481 | 17226789 | Here, we show that human bone marrow-derived mesenchymal stem cells (hMSCs) could be induced to differentiate into functional insulin-producing cells by introduction of the pancreatic duodenal homeobox-1 (PDX-1). |
| 2482 | 17226789 | After being infected with Ad-PDX-1, hMSCs were successfully induced to differentiate into insulin-secreting cells. |
| 2483 | 17226789 | The differentiated PDX-1+ hMSCs expressed multiple islet-cell genes including neurogenin3 (Ngn3), insulin, GK, Glut2, and glucagon, produced and released insulin/C-peptide in a weak glucose-regulated manner. |
| 2484 | 17226789 | Generation of insulin-producing cells from PDX-1 gene-modified human mesenchymal stem cells. |
| 2485 | 17226789 | Here, we show that human bone marrow-derived mesenchymal stem cells (hMSCs) could be induced to differentiate into functional insulin-producing cells by introduction of the pancreatic duodenal homeobox-1 (PDX-1). |
| 2486 | 17226789 | After being infected with Ad-PDX-1, hMSCs were successfully induced to differentiate into insulin-secreting cells. |
| 2487 | 17226789 | The differentiated PDX-1+ hMSCs expressed multiple islet-cell genes including neurogenin3 (Ngn3), insulin, GK, Glut2, and glucagon, produced and released insulin/C-peptide in a weak glucose-regulated manner. |
| 2488 | 17226789 | Generation of insulin-producing cells from PDX-1 gene-modified human mesenchymal stem cells. |
| 2489 | 17226789 | Here, we show that human bone marrow-derived mesenchymal stem cells (hMSCs) could be induced to differentiate into functional insulin-producing cells by introduction of the pancreatic duodenal homeobox-1 (PDX-1). |
| 2490 | 17226789 | After being infected with Ad-PDX-1, hMSCs were successfully induced to differentiate into insulin-secreting cells. |
| 2491 | 17226789 | The differentiated PDX-1+ hMSCs expressed multiple islet-cell genes including neurogenin3 (Ngn3), insulin, GK, Glut2, and glucagon, produced and released insulin/C-peptide in a weak glucose-regulated manner. |
| 2492 | 17226789 | Generation of insulin-producing cells from PDX-1 gene-modified human mesenchymal stem cells. |
| 2493 | 17226789 | Here, we show that human bone marrow-derived mesenchymal stem cells (hMSCs) could be induced to differentiate into functional insulin-producing cells by introduction of the pancreatic duodenal homeobox-1 (PDX-1). |
| 2494 | 17226789 | After being infected with Ad-PDX-1, hMSCs were successfully induced to differentiate into insulin-secreting cells. |
| 2495 | 17226789 | The differentiated PDX-1+ hMSCs expressed multiple islet-cell genes including neurogenin3 (Ngn3), insulin, GK, Glut2, and glucagon, produced and released insulin/C-peptide in a weak glucose-regulated manner. |
| 2496 | 17229937 | Diazoxide upregulated certain genes known to support beta-cell functionality, such as NKX6.1 and PDX1. |
| 2497 | 17235302 | Adenovirus transduction is required for the correction of diabetes using Pdx-1 or Neurogenin-3 in the liver. |
| 2498 | 17235302 | Pancreatic duodenal homeobox-1 (Pdx-1), NeuroD, and Neurogenin-3 (Ngn3) are pancreatic transcription factors important for the development of insulin-producing cells in the liver. |
| 2499 | 17235302 | Adenovirus transduction is required for the correction of diabetes using Pdx-1 or Neurogenin-3 in the liver. |
| 2500 | 17235302 | Pancreatic duodenal homeobox-1 (Pdx-1), NeuroD, and Neurogenin-3 (Ngn3) are pancreatic transcription factors important for the development of insulin-producing cells in the liver. |
| 2501 | 17235568 | We studied beta cell regeneration by analyzing the immunocytochemical expression of the transcription factors, PDX-1, PBX-1, and MEIS2, and that of the potential precursor cell markers, c-Kit and nestin, using the model of streptozotocin (STZ)-induced diabetes in rats. |
| 2502 | 17235568 | PDX-1 expression, but not that of MEIS2 and PBX-1, transiently increased on day 7. c-Kit expression was found to be upregulated in islet cells at all points in time, while nestin expression was lacking. |
| 2503 | 17235568 | These results suggest that temporary upregulation of PDX-1 and prolonged overexpression of c-Kit may play a role during beta cell regeneration. |
| 2504 | 17235568 | We studied beta cell regeneration by analyzing the immunocytochemical expression of the transcription factors, PDX-1, PBX-1, and MEIS2, and that of the potential precursor cell markers, c-Kit and nestin, using the model of streptozotocin (STZ)-induced diabetes in rats. |
| 2505 | 17235568 | PDX-1 expression, but not that of MEIS2 and PBX-1, transiently increased on day 7. c-Kit expression was found to be upregulated in islet cells at all points in time, while nestin expression was lacking. |
| 2506 | 17235568 | These results suggest that temporary upregulation of PDX-1 and prolonged overexpression of c-Kit may play a role during beta cell regeneration. |
| 2507 | 17235568 | We studied beta cell regeneration by analyzing the immunocytochemical expression of the transcription factors, PDX-1, PBX-1, and MEIS2, and that of the potential precursor cell markers, c-Kit and nestin, using the model of streptozotocin (STZ)-induced diabetes in rats. |
| 2508 | 17235568 | PDX-1 expression, but not that of MEIS2 and PBX-1, transiently increased on day 7. c-Kit expression was found to be upregulated in islet cells at all points in time, while nestin expression was lacking. |
| 2509 | 17235568 | These results suggest that temporary upregulation of PDX-1 and prolonged overexpression of c-Kit may play a role during beta cell regeneration. |
| 2510 | 17259388 | Glucotoxicity in the INS-1 rat insulinoma cell line is mediated by the orphan nuclear receptor small heterodimer partner. |
| 2511 | 17259388 | Small heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor that inhibits nuclear receptor signaling in diverse metabolic pathways. |
| 2512 | 17259388 | In this study, we found that sustained culture of INS-1 cells at high glucose concentrations leads to an increase in SHP mRNA expression, followed by a decrease in insulin gene expression. |
| 2513 | 17259388 | Inhibition of endogenous SHP gene expression by small interfering RNA partially restored high-glucose-induced suppression of the insulin gene. |
| 2514 | 17259388 | Adenovirus-mediated overexpression of SHP in INS-1 cells impaired glucose-stimulated insulin secretion as well as insulin gene expression. |
| 2515 | 17259388 | SHP downregulates insulin gene expression via two mechanisms: by downregulating PDX-1 and MafA gene expression and by inhibiting p300-mediated pancreatic duodenal homeobox factor 1-and BETA2-dependent transcriptional activity from the insulin promoter. |
| 2516 | 17263687 | The beta-cell specific transcription factor Nkx6.1 inhibits glucagon gene transcription by interfering with Pax6. |
| 2517 | 17263687 | The transcription factor Nkx6.1 is required for the establishment of functional insulin-producing beta-cells in the endocrine pancreas. |
| 2518 | 17263687 | Overexpression of Nkx6.1 has been shown to inhibit glucagon gene expression while favouring insulin gene activation. |
| 2519 | 17263687 | Down-regulation resulted in the opposite effect, suggesting that absence of Nkx6.1 favours glucagon gene expression. |
| 2520 | 17263687 | To understand the mechanism by which Nkx6.1 suppresses glucagon gene expression, we studied its effect on the glucagon gene promoter activity in non-islet cells using transient transfections and gel-shift analyses. |
| 2521 | 17263687 | In glucagonoma cells transfected with an Nkx6.1-encoding vector, the glucagon promoter activity was reduced by 65%. |
| 2522 | 17263687 | In BHK21 cells, Nkx6.1 inhibited by 93% Pax6-mediated activation of the glucagon promoter, whereas Cdx2/3 and Maf stimulations were unaltered. |
| 2523 | 17263687 | Although Nkx6.1 could interact with both the G1 and G3 element, only the former displayed specificity for Nkx6.1. |
| 2524 | 17263687 | Mutagenesis of the three potential AT-rich motifs within the G1 revealed that only the Pax6-binding site preferentially interacted with Nkx6.1. |
| 2525 | 17263687 | Chromatin immunoprecipitation confirmed interaction of Nkx6.1 with the glucagon promoter and revealed a direct competition for binding between Pax6 and Nkx6.1. |
| 2526 | 17263687 | A weak physical interaction between Pax6 and Nkx6.1 was detected in vitro and in vivo suggesting that Nkx6.1 predominantly inhibits glucagon gene transcription through G1-binding competition. |
| 2527 | 17263687 | We suggest that cell-specific expression of the glucagon gene may only proceed when Nkx6.1, in combination with Pdx1 and Pax4, are silenced in early alpha-cell precursors. |
| 2528 | 17272496 | Concomitantly, downregulation of the pancreas marker Pdx1 was recorded in activin-treated EBs, a phenomenon that was prevented by antagonizing Hedgehog signaling with Hedgehog interacting protein. |
| 2529 | 17292559 | The new drug exenatide, an analog of the incretin hormone glucagon-like peptide-1, may be a worthwhile adjuvant to such fasting therapy, since it tends to counteract the glucolipotoxicity-induced down-regulation of the crucially important beta cell transcription factor IDX-1. |
| 2530 | 17299038 | Fas is a death receptor involved in beta cell apoptosis or proliferation, depending on the activity of the caspase-8 inhibitor FLIP. |
| 2531 | 17299038 | Expression of PDX-1, a beta cell-specific transcription factor regulating insulin gene expression and mitochondrial metabolism, was decreased in Fas-deficient beta cells. |
| 2532 | 17299038 | This led to increased PDX-1 and insulin production independent of changes in cell turnover. |
| 2533 | 17299038 | The results support a previously undescribed role for the Fas pathway in regulating insulin production and release. |
| 2534 | 17299038 | Fas is a death receptor involved in beta cell apoptosis or proliferation, depending on the activity of the caspase-8 inhibitor FLIP. |
| 2535 | 17299038 | Expression of PDX-1, a beta cell-specific transcription factor regulating insulin gene expression and mitochondrial metabolism, was decreased in Fas-deficient beta cells. |
| 2536 | 17299038 | This led to increased PDX-1 and insulin production independent of changes in cell turnover. |
| 2537 | 17299038 | The results support a previously undescribed role for the Fas pathway in regulating insulin production and release. |
| 2538 | 17299998 | Infection with the adenovirus expressing PDX-1, Ngn3, NeuroD, or Pax4 induced the insulin gene expression. |
| 2539 | 17299998 | NeuroD was the most effective inducer of insulin expression in primary duct cells. |
| 2540 | 17299998 | These data suggest that the overexpression of transcription factors, especially NeuroD, facilitates pancreatic stem/progenitor cell differentiation into insulin-producing cells. |
| 2541 | 17303800 | We provide evidence that mouse beta-cells can undergo dedifferentiation in vitro into an insulin-, pdx1-, and glut2-negative state. |
| 2542 | 17315980 | Mutations in the human pdx1 gene are linked to an early onset form of non-insulin-dependent diabetes mellitus, MODY-4. |
| 2543 | 17317781 | Negative regulation of c-Myc transcription by pancreas duodenum homeobox-1. |
| 2544 | 17317781 | The pancreatic and duodenal homeobox factor-1 (Pdx1) is essential for pancreatic development and insulin gene transcription, whereas c-Myc has a deleterious effect on islet function. |
| 2545 | 17317781 | However, the relationship between c-Myc and Pdx1 is poorly concerned. |
| 2546 | 17317781 | Here we demonstrated that Pdx1 could suppress c-Myc promoter activity, which relied on T cell factor (Tcf) binding elements harbored in c-Myc promoter. |
| 2547 | 17317781 | Furthermore, the transcription activity of beta-catenin/Tcf was markedly decreased on Pdx1 expression, but cotransfection of Pdx1 short hairpin RNA abrogated this effect. |
| 2548 | 17317781 | Pdx1 expression did not induce beta-catenin degradation nor did it alter their subcellular distribution. |
| 2549 | 17317781 | The mutation analysis showed that the amino acids (1-209) of Pdx1 harboring an inhibitory domain, which might lead to the reduction of beta-catenin/Tcf/p300 complex levels and attenuate their binding activity with c-Myc promoter sequences. |
| 2550 | 17317781 | Moreover, adenovirus-mediated Pdx1 interference caused cell proliferation and cytokine-induced apoptosis via the dysregulation of c-Myc transcription. |
| 2551 | 17317781 | These results indicated that the Pdx1 functioned as a key regulator for maintenance of beta-cell function, at least in part, through controlling c-Myc expression and the loss of its regulatory function may be an alternative mechanism for beta-cell neogenesis and apoptosis found in diabetes. |
| 2552 | 17317781 | Negative regulation of c-Myc transcription by pancreas duodenum homeobox-1. |
| 2553 | 17317781 | The pancreatic and duodenal homeobox factor-1 (Pdx1) is essential for pancreatic development and insulin gene transcription, whereas c-Myc has a deleterious effect on islet function. |
| 2554 | 17317781 | However, the relationship between c-Myc and Pdx1 is poorly concerned. |
| 2555 | 17317781 | Here we demonstrated that Pdx1 could suppress c-Myc promoter activity, which relied on T cell factor (Tcf) binding elements harbored in c-Myc promoter. |
| 2556 | 17317781 | Furthermore, the transcription activity of beta-catenin/Tcf was markedly decreased on Pdx1 expression, but cotransfection of Pdx1 short hairpin RNA abrogated this effect. |
| 2557 | 17317781 | Pdx1 expression did not induce beta-catenin degradation nor did it alter their subcellular distribution. |
| 2558 | 17317781 | The mutation analysis showed that the amino acids (1-209) of Pdx1 harboring an inhibitory domain, which might lead to the reduction of beta-catenin/Tcf/p300 complex levels and attenuate their binding activity with c-Myc promoter sequences. |
| 2559 | 17317781 | Moreover, adenovirus-mediated Pdx1 interference caused cell proliferation and cytokine-induced apoptosis via the dysregulation of c-Myc transcription. |
| 2560 | 17317781 | These results indicated that the Pdx1 functioned as a key regulator for maintenance of beta-cell function, at least in part, through controlling c-Myc expression and the loss of its regulatory function may be an alternative mechanism for beta-cell neogenesis and apoptosis found in diabetes. |
| 2561 | 17317781 | Negative regulation of c-Myc transcription by pancreas duodenum homeobox-1. |
| 2562 | 17317781 | The pancreatic and duodenal homeobox factor-1 (Pdx1) is essential for pancreatic development and insulin gene transcription, whereas c-Myc has a deleterious effect on islet function. |
| 2563 | 17317781 | However, the relationship between c-Myc and Pdx1 is poorly concerned. |
| 2564 | 17317781 | Here we demonstrated that Pdx1 could suppress c-Myc promoter activity, which relied on T cell factor (Tcf) binding elements harbored in c-Myc promoter. |
| 2565 | 17317781 | Furthermore, the transcription activity of beta-catenin/Tcf was markedly decreased on Pdx1 expression, but cotransfection of Pdx1 short hairpin RNA abrogated this effect. |
| 2566 | 17317781 | Pdx1 expression did not induce beta-catenin degradation nor did it alter their subcellular distribution. |
| 2567 | 17317781 | The mutation analysis showed that the amino acids (1-209) of Pdx1 harboring an inhibitory domain, which might lead to the reduction of beta-catenin/Tcf/p300 complex levels and attenuate their binding activity with c-Myc promoter sequences. |
| 2568 | 17317781 | Moreover, adenovirus-mediated Pdx1 interference caused cell proliferation and cytokine-induced apoptosis via the dysregulation of c-Myc transcription. |
| 2569 | 17317781 | These results indicated that the Pdx1 functioned as a key regulator for maintenance of beta-cell function, at least in part, through controlling c-Myc expression and the loss of its regulatory function may be an alternative mechanism for beta-cell neogenesis and apoptosis found in diabetes. |
| 2570 | 17317781 | Negative regulation of c-Myc transcription by pancreas duodenum homeobox-1. |
| 2571 | 17317781 | The pancreatic and duodenal homeobox factor-1 (Pdx1) is essential for pancreatic development and insulin gene transcription, whereas c-Myc has a deleterious effect on islet function. |
| 2572 | 17317781 | However, the relationship between c-Myc and Pdx1 is poorly concerned. |
| 2573 | 17317781 | Here we demonstrated that Pdx1 could suppress c-Myc promoter activity, which relied on T cell factor (Tcf) binding elements harbored in c-Myc promoter. |
| 2574 | 17317781 | Furthermore, the transcription activity of beta-catenin/Tcf was markedly decreased on Pdx1 expression, but cotransfection of Pdx1 short hairpin RNA abrogated this effect. |
| 2575 | 17317781 | Pdx1 expression did not induce beta-catenin degradation nor did it alter their subcellular distribution. |
| 2576 | 17317781 | The mutation analysis showed that the amino acids (1-209) of Pdx1 harboring an inhibitory domain, which might lead to the reduction of beta-catenin/Tcf/p300 complex levels and attenuate their binding activity with c-Myc promoter sequences. |
| 2577 | 17317781 | Moreover, adenovirus-mediated Pdx1 interference caused cell proliferation and cytokine-induced apoptosis via the dysregulation of c-Myc transcription. |
| 2578 | 17317781 | These results indicated that the Pdx1 functioned as a key regulator for maintenance of beta-cell function, at least in part, through controlling c-Myc expression and the loss of its regulatory function may be an alternative mechanism for beta-cell neogenesis and apoptosis found in diabetes. |
| 2579 | 17317781 | Negative regulation of c-Myc transcription by pancreas duodenum homeobox-1. |
| 2580 | 17317781 | The pancreatic and duodenal homeobox factor-1 (Pdx1) is essential for pancreatic development and insulin gene transcription, whereas c-Myc has a deleterious effect on islet function. |
| 2581 | 17317781 | However, the relationship between c-Myc and Pdx1 is poorly concerned. |
| 2582 | 17317781 | Here we demonstrated that Pdx1 could suppress c-Myc promoter activity, which relied on T cell factor (Tcf) binding elements harbored in c-Myc promoter. |
| 2583 | 17317781 | Furthermore, the transcription activity of beta-catenin/Tcf was markedly decreased on Pdx1 expression, but cotransfection of Pdx1 short hairpin RNA abrogated this effect. |
| 2584 | 17317781 | Pdx1 expression did not induce beta-catenin degradation nor did it alter their subcellular distribution. |
| 2585 | 17317781 | The mutation analysis showed that the amino acids (1-209) of Pdx1 harboring an inhibitory domain, which might lead to the reduction of beta-catenin/Tcf/p300 complex levels and attenuate their binding activity with c-Myc promoter sequences. |
| 2586 | 17317781 | Moreover, adenovirus-mediated Pdx1 interference caused cell proliferation and cytokine-induced apoptosis via the dysregulation of c-Myc transcription. |
| 2587 | 17317781 | These results indicated that the Pdx1 functioned as a key regulator for maintenance of beta-cell function, at least in part, through controlling c-Myc expression and the loss of its regulatory function may be an alternative mechanism for beta-cell neogenesis and apoptosis found in diabetes. |
| 2588 | 17317781 | Negative regulation of c-Myc transcription by pancreas duodenum homeobox-1. |
| 2589 | 17317781 | The pancreatic and duodenal homeobox factor-1 (Pdx1) is essential for pancreatic development and insulin gene transcription, whereas c-Myc has a deleterious effect on islet function. |
| 2590 | 17317781 | However, the relationship between c-Myc and Pdx1 is poorly concerned. |
| 2591 | 17317781 | Here we demonstrated that Pdx1 could suppress c-Myc promoter activity, which relied on T cell factor (Tcf) binding elements harbored in c-Myc promoter. |
| 2592 | 17317781 | Furthermore, the transcription activity of beta-catenin/Tcf was markedly decreased on Pdx1 expression, but cotransfection of Pdx1 short hairpin RNA abrogated this effect. |
| 2593 | 17317781 | Pdx1 expression did not induce beta-catenin degradation nor did it alter their subcellular distribution. |
| 2594 | 17317781 | The mutation analysis showed that the amino acids (1-209) of Pdx1 harboring an inhibitory domain, which might lead to the reduction of beta-catenin/Tcf/p300 complex levels and attenuate their binding activity with c-Myc promoter sequences. |
| 2595 | 17317781 | Moreover, adenovirus-mediated Pdx1 interference caused cell proliferation and cytokine-induced apoptosis via the dysregulation of c-Myc transcription. |
| 2596 | 17317781 | These results indicated that the Pdx1 functioned as a key regulator for maintenance of beta-cell function, at least in part, through controlling c-Myc expression and the loss of its regulatory function may be an alternative mechanism for beta-cell neogenesis and apoptosis found in diabetes. |
| 2597 | 17317781 | Negative regulation of c-Myc transcription by pancreas duodenum homeobox-1. |
| 2598 | 17317781 | The pancreatic and duodenal homeobox factor-1 (Pdx1) is essential for pancreatic development and insulin gene transcription, whereas c-Myc has a deleterious effect on islet function. |
| 2599 | 17317781 | However, the relationship between c-Myc and Pdx1 is poorly concerned. |
| 2600 | 17317781 | Here we demonstrated that Pdx1 could suppress c-Myc promoter activity, which relied on T cell factor (Tcf) binding elements harbored in c-Myc promoter. |
| 2601 | 17317781 | Furthermore, the transcription activity of beta-catenin/Tcf was markedly decreased on Pdx1 expression, but cotransfection of Pdx1 short hairpin RNA abrogated this effect. |
| 2602 | 17317781 | Pdx1 expression did not induce beta-catenin degradation nor did it alter their subcellular distribution. |
| 2603 | 17317781 | The mutation analysis showed that the amino acids (1-209) of Pdx1 harboring an inhibitory domain, which might lead to the reduction of beta-catenin/Tcf/p300 complex levels and attenuate their binding activity with c-Myc promoter sequences. |
| 2604 | 17317781 | Moreover, adenovirus-mediated Pdx1 interference caused cell proliferation and cytokine-induced apoptosis via the dysregulation of c-Myc transcription. |
| 2605 | 17317781 | These results indicated that the Pdx1 functioned as a key regulator for maintenance of beta-cell function, at least in part, through controlling c-Myc expression and the loss of its regulatory function may be an alternative mechanism for beta-cell neogenesis and apoptosis found in diabetes. |
| 2606 | 17317781 | Negative regulation of c-Myc transcription by pancreas duodenum homeobox-1. |
| 2607 | 17317781 | The pancreatic and duodenal homeobox factor-1 (Pdx1) is essential for pancreatic development and insulin gene transcription, whereas c-Myc has a deleterious effect on islet function. |
| 2608 | 17317781 | However, the relationship between c-Myc and Pdx1 is poorly concerned. |
| 2609 | 17317781 | Here we demonstrated that Pdx1 could suppress c-Myc promoter activity, which relied on T cell factor (Tcf) binding elements harbored in c-Myc promoter. |
| 2610 | 17317781 | Furthermore, the transcription activity of beta-catenin/Tcf was markedly decreased on Pdx1 expression, but cotransfection of Pdx1 short hairpin RNA abrogated this effect. |
| 2611 | 17317781 | Pdx1 expression did not induce beta-catenin degradation nor did it alter their subcellular distribution. |
| 2612 | 17317781 | The mutation analysis showed that the amino acids (1-209) of Pdx1 harboring an inhibitory domain, which might lead to the reduction of beta-catenin/Tcf/p300 complex levels and attenuate their binding activity with c-Myc promoter sequences. |
| 2613 | 17317781 | Moreover, adenovirus-mediated Pdx1 interference caused cell proliferation and cytokine-induced apoptosis via the dysregulation of c-Myc transcription. |
| 2614 | 17317781 | These results indicated that the Pdx1 functioned as a key regulator for maintenance of beta-cell function, at least in part, through controlling c-Myc expression and the loss of its regulatory function may be an alternative mechanism for beta-cell neogenesis and apoptosis found in diabetes. |
| 2615 | 17322477 | The effect of mesenchyme was not due to an increase in beta-cell proliferation but was due to increased proliferation of early pancreatic duodenal homeobox-1 (PDX1)-positive progenitor cells, as confirmed by bromodeoxyuridine incorporation. |
| 2616 | 17322477 | Fibroblast growth factor 10 mimicked mesenchyme effects on proliferation of early PDX1(+) progenitor cells and induction of Ngn3 expression. |
| 2617 | 17322477 | The effect of mesenchyme was not due to an increase in beta-cell proliferation but was due to increased proliferation of early pancreatic duodenal homeobox-1 (PDX1)-positive progenitor cells, as confirmed by bromodeoxyuridine incorporation. |
| 2618 | 17322477 | Fibroblast growth factor 10 mimicked mesenchyme effects on proliferation of early PDX1(+) progenitor cells and induction of Ngn3 expression. |
| 2619 | 17327436 | Specifically, we determined patterns of common sequence variation in the genes encoding Gck, Ipf1, Tcf2, and NeuroD1 (MODY2 and MODY4-MODY6, respectively), selected a comprehensive set of 107 tag single nucleotide polymorphisms (SNPs) that captured common variation, and genotyped each in 4,206 patients and control subjects from Sweden, Finland, and Canada (including family-based studies and unrelated case-control subjects). |
| 2620 | 17327436 | We combined these results with our previous studies on HNF4alpha and TCF1 and explicitly tested for gene-gene interactions among these variants and with several known type 2 diabetes susceptibility loci, and we found no genetic interactions between these six genes. |
| 2621 | 17330137 | Two array-based approaches were used, a rat insulinoma cell line (INS-1alphabeta) overexpressing pancreatic duodenum homeobox 1 (pdx-1) and treated with interleukin 1beta (IL-1beta) as well as human pancreatic islets stimulated with a mixture of cytokines. |
| 2622 | 17348806 | Ultimately, 85% percent of the nonendocrine epithelial cells isolated from human pancreatic tissue and cultured in the optimized conditions for 8 days, readily re-expressed pancreatic duodenal homeobox-1 (Pdx1). |
| 2623 | 17381686 | The mouse major histocompatibility complex class I promoter H-2K(b) and the pancreatic-specific promoters insulin and human pdx-1 (area II) performed poorly in islets from all three species. |
| 2624 | 17383157 | Ectopic PDX-1 expression induced pancreatic gene expression and insulin production in the mice livers. |
| 2625 | 17395739 | Some single colonies expressed insulin I, insulin II, and Pdx-1 (pancreatic duodenal homeobox-1), but not glucagon. |
| 2626 | 17403901 | Ptf1a binds to and activates area III, a highly conserved region of the Pdx1 promoter that mediates early pancreas-wide Pdx1 expression. |
| 2627 | 17403901 | The critical pancreatic transcription factor Pdx1 is expressed throughout the pancreas early but enriched in insulin-producing beta cells postnatally. |
| 2628 | 17403901 | Ptf1a binds to and activates area III, a highly conserved region of the Pdx1 promoter that mediates early pancreas-wide Pdx1 expression. |
| 2629 | 17403901 | The critical pancreatic transcription factor Pdx1 is expressed throughout the pancreas early but enriched in insulin-producing beta cells postnatally. |
| 2630 | 17426693 | When transplanted into renal capsules of Streptozotocin (STZ)-treated nude mice, these differentiated human ES cells survived and maintained the expression of beta cell marker genes, including C-peptide, pdx1, glucokinase, nkx6.1, IAPP, pax6 and Tcf1. |
| 2631 | 17433254 | By using real-time RT-PCR, early mRNA expressions of Pdx1, as well as the Sox17 and Foxa2 genes, were observed to be significantly activated in SB-PDMSCs, followed by the expression of mature pancreas-related genes (insulin, glucagon, and somatostatin). |
| 2632 | 17449132 | Role of PDX-1 and MafA as a potential therapeutic target for diabetes. |
| 2633 | 17449132 | Also, PDX-1 has potency to induce insulin-producing cells from non-beta-cells in various tissues, and PDX-1-VP16 fusion protein more efficiently induces insulin-producing cells, especially in the presence of NeuroD or Ngn3. |
| 2634 | 17449132 | MafA is a recently isolated beta-cell-specific transcription factor which functions as a potent activator of insulin gene transcription. |
| 2635 | 17449132 | During pancreas development, MafA expression is first detected at the beginning of the principal phase of insulin-producing cell production. |
| 2636 | 17449132 | Furthermore, MafA markedly enhances insulin gene promoter activity and ameliorates glucose tolerance in diabetic mice, especially in the presence of PDX-1 and NeuroD. |
| 2637 | 17449132 | Taken together, PDX-1 and MafA play a crucial role in inducing surrogate beta-cells and could be a therapeutic target for diabetes. |
| 2638 | 17449132 | Role of PDX-1 and MafA as a potential therapeutic target for diabetes. |
| 2639 | 17449132 | Also, PDX-1 has potency to induce insulin-producing cells from non-beta-cells in various tissues, and PDX-1-VP16 fusion protein more efficiently induces insulin-producing cells, especially in the presence of NeuroD or Ngn3. |
| 2640 | 17449132 | MafA is a recently isolated beta-cell-specific transcription factor which functions as a potent activator of insulin gene transcription. |
| 2641 | 17449132 | During pancreas development, MafA expression is first detected at the beginning of the principal phase of insulin-producing cell production. |
| 2642 | 17449132 | Furthermore, MafA markedly enhances insulin gene promoter activity and ameliorates glucose tolerance in diabetic mice, especially in the presence of PDX-1 and NeuroD. |
| 2643 | 17449132 | Taken together, PDX-1 and MafA play a crucial role in inducing surrogate beta-cells and could be a therapeutic target for diabetes. |
| 2644 | 17449132 | Role of PDX-1 and MafA as a potential therapeutic target for diabetes. |
| 2645 | 17449132 | Also, PDX-1 has potency to induce insulin-producing cells from non-beta-cells in various tissues, and PDX-1-VP16 fusion protein more efficiently induces insulin-producing cells, especially in the presence of NeuroD or Ngn3. |
| 2646 | 17449132 | MafA is a recently isolated beta-cell-specific transcription factor which functions as a potent activator of insulin gene transcription. |
| 2647 | 17449132 | During pancreas development, MafA expression is first detected at the beginning of the principal phase of insulin-producing cell production. |
| 2648 | 17449132 | Furthermore, MafA markedly enhances insulin gene promoter activity and ameliorates glucose tolerance in diabetic mice, especially in the presence of PDX-1 and NeuroD. |
| 2649 | 17449132 | Taken together, PDX-1 and MafA play a crucial role in inducing surrogate beta-cells and could be a therapeutic target for diabetes. |
| 2650 | 17449132 | Role of PDX-1 and MafA as a potential therapeutic target for diabetes. |
| 2651 | 17449132 | Also, PDX-1 has potency to induce insulin-producing cells from non-beta-cells in various tissues, and PDX-1-VP16 fusion protein more efficiently induces insulin-producing cells, especially in the presence of NeuroD or Ngn3. |
| 2652 | 17449132 | MafA is a recently isolated beta-cell-specific transcription factor which functions as a potent activator of insulin gene transcription. |
| 2653 | 17449132 | During pancreas development, MafA expression is first detected at the beginning of the principal phase of insulin-producing cell production. |
| 2654 | 17449132 | Furthermore, MafA markedly enhances insulin gene promoter activity and ameliorates glucose tolerance in diabetic mice, especially in the presence of PDX-1 and NeuroD. |
| 2655 | 17449132 | Taken together, PDX-1 and MafA play a crucial role in inducing surrogate beta-cells and could be a therapeutic target for diabetes. |
| 2656 | 17451835 | Both Pdx-1 and NeuroD1 genes are requisite for the maintenance of insulin gene expression in ES-derived differentiated cells. |
| 2657 | 17451835 | We have established an ES cell line in which exogenous Pdx-1 expression was precisely regulated by the Tet-off system integrated into the ROSA26 locus and succeeded to produce insulin-producing cells. |
| 2658 | 17451835 | The Pdx-1 expressing final differentiated insulin-positive cells can be maintained for more than 2 months. |
| 2659 | 17451835 | However, in spite of their induced expression of Pdx-1, the repeated passages of cells lost their capacity to express insulin and NeuroD1 gene. |
| 2660 | 17451835 | These results suggested that maintenance of the property of insulin-producing cells derived from ES cells could be achieved by synergistic expression of Pdx-1 and NeuroD1. |
| 2661 | 17451835 | Both Pdx-1 and NeuroD1 genes are requisite for the maintenance of insulin gene expression in ES-derived differentiated cells. |
| 2662 | 17451835 | We have established an ES cell line in which exogenous Pdx-1 expression was precisely regulated by the Tet-off system integrated into the ROSA26 locus and succeeded to produce insulin-producing cells. |
| 2663 | 17451835 | The Pdx-1 expressing final differentiated insulin-positive cells can be maintained for more than 2 months. |
| 2664 | 17451835 | However, in spite of their induced expression of Pdx-1, the repeated passages of cells lost their capacity to express insulin and NeuroD1 gene. |
| 2665 | 17451835 | These results suggested that maintenance of the property of insulin-producing cells derived from ES cells could be achieved by synergistic expression of Pdx-1 and NeuroD1. |
| 2666 | 17451835 | Both Pdx-1 and NeuroD1 genes are requisite for the maintenance of insulin gene expression in ES-derived differentiated cells. |
| 2667 | 17451835 | We have established an ES cell line in which exogenous Pdx-1 expression was precisely regulated by the Tet-off system integrated into the ROSA26 locus and succeeded to produce insulin-producing cells. |
| 2668 | 17451835 | The Pdx-1 expressing final differentiated insulin-positive cells can be maintained for more than 2 months. |
| 2669 | 17451835 | However, in spite of their induced expression of Pdx-1, the repeated passages of cells lost their capacity to express insulin and NeuroD1 gene. |
| 2670 | 17451835 | These results suggested that maintenance of the property of insulin-producing cells derived from ES cells could be achieved by synergistic expression of Pdx-1 and NeuroD1. |
| 2671 | 17451835 | Both Pdx-1 and NeuroD1 genes are requisite for the maintenance of insulin gene expression in ES-derived differentiated cells. |
| 2672 | 17451835 | We have established an ES cell line in which exogenous Pdx-1 expression was precisely regulated by the Tet-off system integrated into the ROSA26 locus and succeeded to produce insulin-producing cells. |
| 2673 | 17451835 | The Pdx-1 expressing final differentiated insulin-positive cells can be maintained for more than 2 months. |
| 2674 | 17451835 | However, in spite of their induced expression of Pdx-1, the repeated passages of cells lost their capacity to express insulin and NeuroD1 gene. |
| 2675 | 17451835 | These results suggested that maintenance of the property of insulin-producing cells derived from ES cells could be achieved by synergistic expression of Pdx-1 and NeuroD1. |
| 2676 | 17451835 | Both Pdx-1 and NeuroD1 genes are requisite for the maintenance of insulin gene expression in ES-derived differentiated cells. |
| 2677 | 17451835 | We have established an ES cell line in which exogenous Pdx-1 expression was precisely regulated by the Tet-off system integrated into the ROSA26 locus and succeeded to produce insulin-producing cells. |
| 2678 | 17451835 | The Pdx-1 expressing final differentiated insulin-positive cells can be maintained for more than 2 months. |
| 2679 | 17451835 | However, in spite of their induced expression of Pdx-1, the repeated passages of cells lost their capacity to express insulin and NeuroD1 gene. |
| 2680 | 17451835 | These results suggested that maintenance of the property of insulin-producing cells derived from ES cells could be achieved by synergistic expression of Pdx-1 and NeuroD1. |
| 2681 | 17460716 | Reversal of streptozotocin-induced diabetes in rats by gene therapy with betacellulin and pancreatic duodenal homeobox-1. |
| 2682 | 17460716 | Ultrasound-targeted microbubble destruction (UTMD) was used to direct betacellulin (BTC) and pancreatic duodenal homeobox-1 (PDX1) to rat pancreas 48 h after islet destruction by streptozotocin (STZ). |
| 2683 | 17460716 | However, in rats treated with both BTC and PDX1, blood glucose remained below 200 mg/dl throughout day 10. |
| 2684 | 17460716 | Histology demonstrated islet-like clusters of glucagon-staining cells in the rats treated with BTC and PDX1, but these clusters disappeared by 30 days after UTMD treatment. |
| 2685 | 17460716 | Reversal of streptozotocin-induced diabetes in rats by gene therapy with betacellulin and pancreatic duodenal homeobox-1. |
| 2686 | 17460716 | Ultrasound-targeted microbubble destruction (UTMD) was used to direct betacellulin (BTC) and pancreatic duodenal homeobox-1 (PDX1) to rat pancreas 48 h after islet destruction by streptozotocin (STZ). |
| 2687 | 17460716 | However, in rats treated with both BTC and PDX1, blood glucose remained below 200 mg/dl throughout day 10. |
| 2688 | 17460716 | Histology demonstrated islet-like clusters of glucagon-staining cells in the rats treated with BTC and PDX1, but these clusters disappeared by 30 days after UTMD treatment. |
| 2689 | 17460716 | Reversal of streptozotocin-induced diabetes in rats by gene therapy with betacellulin and pancreatic duodenal homeobox-1. |
| 2690 | 17460716 | Ultrasound-targeted microbubble destruction (UTMD) was used to direct betacellulin (BTC) and pancreatic duodenal homeobox-1 (PDX1) to rat pancreas 48 h after islet destruction by streptozotocin (STZ). |
| 2691 | 17460716 | However, in rats treated with both BTC and PDX1, blood glucose remained below 200 mg/dl throughout day 10. |
| 2692 | 17460716 | Histology demonstrated islet-like clusters of glucagon-staining cells in the rats treated with BTC and PDX1, but these clusters disappeared by 30 days after UTMD treatment. |
| 2693 | 17460896 | The epithelial cells expressed PDX-1, PCNA, CK-7, CK-19, Nestin, Glut2, and Vimentin, but Insulin was undetected. |
| 2694 | 17460896 | The cells expressed CD29, CD44, and CD166, but did not express CD11a, CD14, CD34, CD45, CD90, CD105, and CD117. |
| 2695 | 17467845 | In real-time RT-PCR, PDX-1, insulin, GLUT2 and prohormone convertase 1/3 gene expression in islets was markedly lower in old rats (33%, 13%, 20% and 34%, respectively) and old mice (56%, 42%, 28% and 22%, respectively) compared with young animals. |
| 2696 | 17467845 | On the other hand, genes not specifically related to beta cell-specific function, such as caspase 3, superoxide dismutase 2 and glycerol kinase were not significantly different in expression in islets according to age. |
| 2697 | 17467845 | In conclusion, with increasing age, insulin secretory function of islets deteriorates accompanied with a decrease in expression of beta cell-specific genes including PDX-1. |
| 2698 | 17467845 | In real-time RT-PCR, PDX-1, insulin, GLUT2 and prohormone convertase 1/3 gene expression in islets was markedly lower in old rats (33%, 13%, 20% and 34%, respectively) and old mice (56%, 42%, 28% and 22%, respectively) compared with young animals. |
| 2699 | 17467845 | On the other hand, genes not specifically related to beta cell-specific function, such as caspase 3, superoxide dismutase 2 and glycerol kinase were not significantly different in expression in islets according to age. |
| 2700 | 17467845 | In conclusion, with increasing age, insulin secretory function of islets deteriorates accompanied with a decrease in expression of beta cell-specific genes including PDX-1. |
| 2701 | 17490618 | Phosphorylation events implicating p38 and PI3K mediate tungstate-effects in MIN6 beta cells. |
| 2702 | 17490618 | Tungstate treatment induced phosphorylation and subsequent activation of p38 and PI3K which in turn are implicated in tungstate PDX-1 nuclear localization and activation. |
| 2703 | 17490618 | These results show a direct involvement of p38 and PI3K phosphorylation in the mechanism of action of tungstate in the beta cell. |
| 2704 | 17510217 | In this 36-day protocol, hESCs were treated with sodium butyrate and activin A to generate definitive endoderm coexpressing CXCR4 and Sox17, and CXCR4 and Foxa2. |
| 2705 | 17510217 | The endoderm population was then converted into cellular aggregates and further differentiated to Pdx1-expressing pancreatic endoderm in the presence of epidermal growth factor, basic fibroblast growth factor, and noggin. |
| 2706 | 17510217 | The aggregates were finally matured in the presence of insulin-like growth factor II and nicotinamide. |
| 2707 | 17510498 | The expression pattern of FoxO1 during pancreatic organogenesis is similar to that of Pdx1, Nkx2.2 and Pax4, transcription factors known to be critical for beta cell development. |
| 2708 | 17510498 | FoxO1 is expressed in a subset of pancreatic duct cells, in which insulin and/or Pdx1 are occasionally expressed. |
| 2709 | 17510498 | FoxO1 inhibits beta cell proliferation through suppression of Pdx1 by competing with FoxA2 and protects against beta cell failure induced by oxidative stress through NeuroD and MafA induction. |
| 2710 | 17510498 | The expression pattern of FoxO1 during pancreatic organogenesis is similar to that of Pdx1, Nkx2.2 and Pax4, transcription factors known to be critical for beta cell development. |
| 2711 | 17510498 | FoxO1 is expressed in a subset of pancreatic duct cells, in which insulin and/or Pdx1 are occasionally expressed. |
| 2712 | 17510498 | FoxO1 inhibits beta cell proliferation through suppression of Pdx1 by competing with FoxA2 and protects against beta cell failure induced by oxidative stress through NeuroD and MafA induction. |
| 2713 | 17510498 | The expression pattern of FoxO1 during pancreatic organogenesis is similar to that of Pdx1, Nkx2.2 and Pax4, transcription factors known to be critical for beta cell development. |
| 2714 | 17510498 | FoxO1 is expressed in a subset of pancreatic duct cells, in which insulin and/or Pdx1 are occasionally expressed. |
| 2715 | 17510498 | FoxO1 inhibits beta cell proliferation through suppression of Pdx1 by competing with FoxA2 and protects against beta cell failure induced by oxidative stress through NeuroD and MafA induction. |
| 2716 | 17512083 | Besides the well-established genes including Pdx-1 and Ngn-3, we propose the nestin and clusterin as the new morphogenic factors for beta-cell neogenesis and their functional associations. |
| 2717 | 17512083 | In in vitro culture, the nestin-rich epithelial cells of the neogenic ductules also displayed extensive self-replication leading to monolayer of epithelial cell explants and transformed into the insulin secreting beta cells as well as duct cells. |
| 2718 | 17512083 | Insulin expression, both insulin mRNA and peptide levels, was increased and showed glucose dependent manner by ectopic expression of clusterin upon the culture of neogenic ductules when compared to the mock-transfected control, implying that the duct cells transformed functional beta cells. |
| 2719 | 17512083 | We observed that clusterin over-expression led to up-regulation of Pdx-1 and Ngn-3, and clusterin levels were increased upon the transfection of cDNAs of Pdx-1 or Ngn-3, suggesting a close functional association of these morphogenic factors. |
| 2720 | 17512083 | In conclusion, we suggest that adult pancreatic stem cells can be recapitulated for neogenesis of insulin secreting beta cells not only by reactivation Pdx-1 and Ngn-3, the classical differentiation factors for pancreas development, but also by the intervention of new morphogenic factors including nestin and clusterin. |
| 2721 | 17512083 | In particular, by modulation of Pdx-1 and Ngn-3, clusterin induces remarkable differentiation of the functional beta cells secreting insulin in response to glucose stimulation. |
| 2722 | 17512083 | Besides the well-established genes including Pdx-1 and Ngn-3, we propose the nestin and clusterin as the new morphogenic factors for beta-cell neogenesis and their functional associations. |
| 2723 | 17512083 | In in vitro culture, the nestin-rich epithelial cells of the neogenic ductules also displayed extensive self-replication leading to monolayer of epithelial cell explants and transformed into the insulin secreting beta cells as well as duct cells. |
| 2724 | 17512083 | Insulin expression, both insulin mRNA and peptide levels, was increased and showed glucose dependent manner by ectopic expression of clusterin upon the culture of neogenic ductules when compared to the mock-transfected control, implying that the duct cells transformed functional beta cells. |
| 2725 | 17512083 | We observed that clusterin over-expression led to up-regulation of Pdx-1 and Ngn-3, and clusterin levels were increased upon the transfection of cDNAs of Pdx-1 or Ngn-3, suggesting a close functional association of these morphogenic factors. |
| 2726 | 17512083 | In conclusion, we suggest that adult pancreatic stem cells can be recapitulated for neogenesis of insulin secreting beta cells not only by reactivation Pdx-1 and Ngn-3, the classical differentiation factors for pancreas development, but also by the intervention of new morphogenic factors including nestin and clusterin. |
| 2727 | 17512083 | In particular, by modulation of Pdx-1 and Ngn-3, clusterin induces remarkable differentiation of the functional beta cells secreting insulin in response to glucose stimulation. |
| 2728 | 17512083 | Besides the well-established genes including Pdx-1 and Ngn-3, we propose the nestin and clusterin as the new morphogenic factors for beta-cell neogenesis and their functional associations. |
| 2729 | 17512083 | In in vitro culture, the nestin-rich epithelial cells of the neogenic ductules also displayed extensive self-replication leading to monolayer of epithelial cell explants and transformed into the insulin secreting beta cells as well as duct cells. |
| 2730 | 17512083 | Insulin expression, both insulin mRNA and peptide levels, was increased and showed glucose dependent manner by ectopic expression of clusterin upon the culture of neogenic ductules when compared to the mock-transfected control, implying that the duct cells transformed functional beta cells. |
| 2731 | 17512083 | We observed that clusterin over-expression led to up-regulation of Pdx-1 and Ngn-3, and clusterin levels were increased upon the transfection of cDNAs of Pdx-1 or Ngn-3, suggesting a close functional association of these morphogenic factors. |
| 2732 | 17512083 | In conclusion, we suggest that adult pancreatic stem cells can be recapitulated for neogenesis of insulin secreting beta cells not only by reactivation Pdx-1 and Ngn-3, the classical differentiation factors for pancreas development, but also by the intervention of new morphogenic factors including nestin and clusterin. |
| 2733 | 17512083 | In particular, by modulation of Pdx-1 and Ngn-3, clusterin induces remarkable differentiation of the functional beta cells secreting insulin in response to glucose stimulation. |
| 2734 | 17512083 | Besides the well-established genes including Pdx-1 and Ngn-3, we propose the nestin and clusterin as the new morphogenic factors for beta-cell neogenesis and their functional associations. |
| 2735 | 17512083 | In in vitro culture, the nestin-rich epithelial cells of the neogenic ductules also displayed extensive self-replication leading to monolayer of epithelial cell explants and transformed into the insulin secreting beta cells as well as duct cells. |
| 2736 | 17512083 | Insulin expression, both insulin mRNA and peptide levels, was increased and showed glucose dependent manner by ectopic expression of clusterin upon the culture of neogenic ductules when compared to the mock-transfected control, implying that the duct cells transformed functional beta cells. |
| 2737 | 17512083 | We observed that clusterin over-expression led to up-regulation of Pdx-1 and Ngn-3, and clusterin levels were increased upon the transfection of cDNAs of Pdx-1 or Ngn-3, suggesting a close functional association of these morphogenic factors. |
| 2738 | 17512083 | In conclusion, we suggest that adult pancreatic stem cells can be recapitulated for neogenesis of insulin secreting beta cells not only by reactivation Pdx-1 and Ngn-3, the classical differentiation factors for pancreas development, but also by the intervention of new morphogenic factors including nestin and clusterin. |
| 2739 | 17512083 | In particular, by modulation of Pdx-1 and Ngn-3, clusterin induces remarkable differentiation of the functional beta cells secreting insulin in response to glucose stimulation. |
| 2740 | 17615265 | The pancreatic duodenal homeobox 1 (Pdx1) gene was expressed in BM-MSC from 14 human donors, and the extent of differentiation of these cells toward the beta-cell phenotype was evaluated. |
| 2741 | 17706592 | Insulin promoter assay showed that Pdx1 highly activates insulin promoter when combined with Ngn3. |
| 2742 | 17709883 | The molecular mechanisms responsible for the glucose toxic effect on beta cell function involves disappearance of two important regulators of insulin promoter activity, PDX-1 and MafA. |
| 2743 | 17717015 | Moreover, confocal microscopy showed colocalization of insulin and pancreas duodenum homeobox-1 (PDX-1) in both endocrine and exocrine pancreas. |
| 2744 | 17717015 | This increase in insulin-expressing cells was accompanied by increased cell proliferation (observed by proliferating cell nuclear antigen-PCNA immunopositivity) which occurred in a regulated manner since it was associated with increased apoptosis (detected by the TUNEL method). |
| 2745 | 17717015 | Furthermore, L-arginine enhanced both nuclear factor-kB (NF-kB) and neuronal nitric oxide synthase (nNOS) immunopositivities. |
| 2746 | 17784830 | By day 34, Pdx1+ cells comprise between 5% and 20% of the total cell population and Insulin gene expression is up-regulated, with release of C-peptide into the culture medium. |
| 2747 | 17785922 | It is produced exclusively by pancreatic islet beta-cells. beta-cell-enriched transcription factors, such as Pdx1 and Beta2, have dual roles in the activation of the insulin gene promoter establishing beta-cell-specific insulin expression, and in the regulation of beta-cell differentiation. |
| 2748 | 17785922 | It was shown that MafA, a beta-cell-specific member of the Maf family of transcription factors, binds to the conserved C1/RIPE3b element of the insulin promoter. |
| 2749 | 17785922 | MafA acts synergistically with Pdx1 and Beta2 to activate the insulin gene promoter, and mice with a targeted deletion of mafA develop age-dependent diabetes. |
| 2750 | 17785922 | MafA also regulates genes involved in beta-cell function such as Glucose transporter 2, Glucagons-like peptide 1 receptor, and Prohormone convertase 1/3. |
| 2751 | 17785922 | This review summarizes recent progress in determining the functions and roles of MafA in the regulation of insulin gene transcription in beta-cells. |
| 2752 | 17785922 | It is produced exclusively by pancreatic islet beta-cells. beta-cell-enriched transcription factors, such as Pdx1 and Beta2, have dual roles in the activation of the insulin gene promoter establishing beta-cell-specific insulin expression, and in the regulation of beta-cell differentiation. |
| 2753 | 17785922 | It was shown that MafA, a beta-cell-specific member of the Maf family of transcription factors, binds to the conserved C1/RIPE3b element of the insulin promoter. |
| 2754 | 17785922 | MafA acts synergistically with Pdx1 and Beta2 to activate the insulin gene promoter, and mice with a targeted deletion of mafA develop age-dependent diabetes. |
| 2755 | 17785922 | MafA also regulates genes involved in beta-cell function such as Glucose transporter 2, Glucagons-like peptide 1 receptor, and Prohormone convertase 1/3. |
| 2756 | 17785922 | This review summarizes recent progress in determining the functions and roles of MafA in the regulation of insulin gene transcription in beta-cells. |
| 2757 | 17909627 | To explore the impact of disrupting leptin signaling in the pancreas on beta cell growth and/or function, we created pancreas-specific leptin receptor (ObR) KOs using mice expressing Cre recombinase under the control of the pancreatic and duodenal homeobox 1 (Pdx1) promoter. |
| 2758 | 17909627 | Similar effects on p70S6K were observed in MIN6 beta cells with knockdown of the ObR gene, suggesting crosstalk between leptin and insulin signaling pathways. |
| 2759 | 17919187 | This effect of SREBP-1c involves multiple functional pathways required for insulin secretion from beta cells: (i) decreased ATP caused by energy consumption through lipogenesis and uncoupling protein-2 (UCP-2) activation; (ii) repressed IRS-2 and pancreas duodenum homeobox 1 (PDX1) expression, leading to impaired beta-cell mass; and (iii) impaired post-ATP membrane voltage-dependent steps of the insulin secretion pathway caused by upregulated granuphilin and other ion channel proteins. |
| 2760 | 17932425 | We show that stepwise differentiation of embryonic stem cells using successive in vivo patterning signals can lead to simultaneous induction of Ptf1a and Pdx1 expression. |
| 2761 | 17938503 | PDX-1 and MafA play a crucial role in pancreatic beta-cell differentiation and maintenance of mature beta-cell function. |
| 2762 | 17938503 | In mature beta-cells, PDX-1 transactivates the insulin and other genes involved in glucose sensing and metabolism such as GLUT2 and glucokinase. |
| 2763 | 17938503 | MafA is a recently isolated beta-cell-specific transcription factor which functions as a potent activator of insulin gene transcription. |
| 2764 | 17938503 | On the other hand, under diabetic conditions, expression and/or activities of PDX-1 and MafA in beta-cells are reduced, which leads to suppression of insulin biosynthesis and secretion. |
| 2765 | 17938503 | PDX-1 and MafA play a crucial role in pancreatic beta-cell differentiation and maintenance of mature beta-cell function. |
| 2766 | 17938503 | In mature beta-cells, PDX-1 transactivates the insulin and other genes involved in glucose sensing and metabolism such as GLUT2 and glucokinase. |
| 2767 | 17938503 | MafA is a recently isolated beta-cell-specific transcription factor which functions as a potent activator of insulin gene transcription. |
| 2768 | 17938503 | On the other hand, under diabetic conditions, expression and/or activities of PDX-1 and MafA in beta-cells are reduced, which leads to suppression of insulin biosynthesis and secretion. |
| 2769 | 17938503 | PDX-1 and MafA play a crucial role in pancreatic beta-cell differentiation and maintenance of mature beta-cell function. |
| 2770 | 17938503 | In mature beta-cells, PDX-1 transactivates the insulin and other genes involved in glucose sensing and metabolism such as GLUT2 and glucokinase. |
| 2771 | 17938503 | MafA is a recently isolated beta-cell-specific transcription factor which functions as a potent activator of insulin gene transcription. |
| 2772 | 17938503 | On the other hand, under diabetic conditions, expression and/or activities of PDX-1 and MafA in beta-cells are reduced, which leads to suppression of insulin biosynthesis and secretion. |
| 2773 | 17979180 | Unlike previous work, with persistent expression of Pdx-1, EGFP/Pdx-1 LEPCs acquired the phenotype of pancreatic endocrine progenitor cells rather than giving rise to insulin-producing cells directly. |
| 2774 | 17979180 | EGFP/Pdx-1 LEPCs proliferated vigorously and expressed the crucial transcription factors involved in beta cell development, including Ngn3, NeuroD, Nkx2.2, Nkx6.1, Pax4, Pax6, Isl1, MafA and endogenous Pdx-1, but did not secrete insulin. |
| 2775 | 17979180 | When transplanted into diabetic SCID mice, EGFP/Pdx-1 LEPCs ameliorated hyperglycemia by secreting insulin in a glucose regulated manner. |
| 2776 | 17979180 | Unlike previous work, with persistent expression of Pdx-1, EGFP/Pdx-1 LEPCs acquired the phenotype of pancreatic endocrine progenitor cells rather than giving rise to insulin-producing cells directly. |
| 2777 | 17979180 | EGFP/Pdx-1 LEPCs proliferated vigorously and expressed the crucial transcription factors involved in beta cell development, including Ngn3, NeuroD, Nkx2.2, Nkx6.1, Pax4, Pax6, Isl1, MafA and endogenous Pdx-1, but did not secrete insulin. |
| 2778 | 17979180 | When transplanted into diabetic SCID mice, EGFP/Pdx-1 LEPCs ameliorated hyperglycemia by secreting insulin in a glucose regulated manner. |
| 2779 | 17979180 | Unlike previous work, with persistent expression of Pdx-1, EGFP/Pdx-1 LEPCs acquired the phenotype of pancreatic endocrine progenitor cells rather than giving rise to insulin-producing cells directly. |
| 2780 | 17979180 | EGFP/Pdx-1 LEPCs proliferated vigorously and expressed the crucial transcription factors involved in beta cell development, including Ngn3, NeuroD, Nkx2.2, Nkx6.1, Pax4, Pax6, Isl1, MafA and endogenous Pdx-1, but did not secrete insulin. |
| 2781 | 17979180 | When transplanted into diabetic SCID mice, EGFP/Pdx-1 LEPCs ameliorated hyperglycemia by secreting insulin in a glucose regulated manner. |
| 2782 | 17991720 | Peroxisome proliferator-activated receptor-alpha regulates the expression of pancreatic/duodenal homeobox-1 in rat insulinoma (INS-1) cells and ameliorates glucose-induced insulin secretion impaired by palmitate. |
| 2783 | 17991720 | Both peroxisome proliferator-activated receptor-alpha (PPARalpha) and pancreatic/duodenal homeobox-1 (PDX-1) have been reported to be associated with glucose-stimulated insulin secretion (GSIS), but the relationship between PPARalpha and PDX-1 is not yet fully understood. |
| 2784 | 17991720 | In the present study, we tested the hypothesis that PPARalpha regulates the expression of PDX-1 in beta-cells. |
| 2785 | 17991720 | In turn, this enhanced expression led to an increase in PDX-1 mRNA and nuclear protein, as well as DNA binding activity of PDX-1 with the insulin promoter. |
| 2786 | 17991720 | Accordingly, the expression of the PDX-1 downstream targets, insulin and glucose transporter-2, increased, resulting in increased intracellular insulin content and GSIS. |
| 2787 | 17991720 | Treatment with MK886 inhibited expression of PPARalpha, blocking PPARalpha-regulated PDX-1 expression, and the downstream transcription events of PDX-1. |
| 2788 | 17991720 | Collectively, these results demonstrate a regulatory relationship between PPARalpha and PDX-1 in INS-1 cells. |
| 2789 | 17991720 | Furthermore, PPARalpha activation potentiates GSIS under elevated palmitate conditions possibly via up-regulation of PDX-1. |
| 2790 | 17991720 | Peroxisome proliferator-activated receptor-alpha regulates the expression of pancreatic/duodenal homeobox-1 in rat insulinoma (INS-1) cells and ameliorates glucose-induced insulin secretion impaired by palmitate. |
| 2791 | 17991720 | Both peroxisome proliferator-activated receptor-alpha (PPARalpha) and pancreatic/duodenal homeobox-1 (PDX-1) have been reported to be associated with glucose-stimulated insulin secretion (GSIS), but the relationship between PPARalpha and PDX-1 is not yet fully understood. |
| 2792 | 17991720 | In the present study, we tested the hypothesis that PPARalpha regulates the expression of PDX-1 in beta-cells. |
| 2793 | 17991720 | In turn, this enhanced expression led to an increase in PDX-1 mRNA and nuclear protein, as well as DNA binding activity of PDX-1 with the insulin promoter. |
| 2794 | 17991720 | Accordingly, the expression of the PDX-1 downstream targets, insulin and glucose transporter-2, increased, resulting in increased intracellular insulin content and GSIS. |
| 2795 | 17991720 | Treatment with MK886 inhibited expression of PPARalpha, blocking PPARalpha-regulated PDX-1 expression, and the downstream transcription events of PDX-1. |
| 2796 | 17991720 | Collectively, these results demonstrate a regulatory relationship between PPARalpha and PDX-1 in INS-1 cells. |
| 2797 | 17991720 | Furthermore, PPARalpha activation potentiates GSIS under elevated palmitate conditions possibly via up-regulation of PDX-1. |
| 2798 | 17991720 | Peroxisome proliferator-activated receptor-alpha regulates the expression of pancreatic/duodenal homeobox-1 in rat insulinoma (INS-1) cells and ameliorates glucose-induced insulin secretion impaired by palmitate. |
| 2799 | 17991720 | Both peroxisome proliferator-activated receptor-alpha (PPARalpha) and pancreatic/duodenal homeobox-1 (PDX-1) have been reported to be associated with glucose-stimulated insulin secretion (GSIS), but the relationship between PPARalpha and PDX-1 is not yet fully understood. |
| 2800 | 17991720 | In the present study, we tested the hypothesis that PPARalpha regulates the expression of PDX-1 in beta-cells. |
| 2801 | 17991720 | In turn, this enhanced expression led to an increase in PDX-1 mRNA and nuclear protein, as well as DNA binding activity of PDX-1 with the insulin promoter. |
| 2802 | 17991720 | Accordingly, the expression of the PDX-1 downstream targets, insulin and glucose transporter-2, increased, resulting in increased intracellular insulin content and GSIS. |
| 2803 | 17991720 | Treatment with MK886 inhibited expression of PPARalpha, blocking PPARalpha-regulated PDX-1 expression, and the downstream transcription events of PDX-1. |
| 2804 | 17991720 | Collectively, these results demonstrate a regulatory relationship between PPARalpha and PDX-1 in INS-1 cells. |
| 2805 | 17991720 | Furthermore, PPARalpha activation potentiates GSIS under elevated palmitate conditions possibly via up-regulation of PDX-1. |
| 2806 | 17991720 | Peroxisome proliferator-activated receptor-alpha regulates the expression of pancreatic/duodenal homeobox-1 in rat insulinoma (INS-1) cells and ameliorates glucose-induced insulin secretion impaired by palmitate. |
| 2807 | 17991720 | Both peroxisome proliferator-activated receptor-alpha (PPARalpha) and pancreatic/duodenal homeobox-1 (PDX-1) have been reported to be associated with glucose-stimulated insulin secretion (GSIS), but the relationship between PPARalpha and PDX-1 is not yet fully understood. |
| 2808 | 17991720 | In the present study, we tested the hypothesis that PPARalpha regulates the expression of PDX-1 in beta-cells. |
| 2809 | 17991720 | In turn, this enhanced expression led to an increase in PDX-1 mRNA and nuclear protein, as well as DNA binding activity of PDX-1 with the insulin promoter. |
| 2810 | 17991720 | Accordingly, the expression of the PDX-1 downstream targets, insulin and glucose transporter-2, increased, resulting in increased intracellular insulin content and GSIS. |
| 2811 | 17991720 | Treatment with MK886 inhibited expression of PPARalpha, blocking PPARalpha-regulated PDX-1 expression, and the downstream transcription events of PDX-1. |
| 2812 | 17991720 | Collectively, these results demonstrate a regulatory relationship between PPARalpha and PDX-1 in INS-1 cells. |
| 2813 | 17991720 | Furthermore, PPARalpha activation potentiates GSIS under elevated palmitate conditions possibly via up-regulation of PDX-1. |
| 2814 | 17991720 | Peroxisome proliferator-activated receptor-alpha regulates the expression of pancreatic/duodenal homeobox-1 in rat insulinoma (INS-1) cells and ameliorates glucose-induced insulin secretion impaired by palmitate. |
| 2815 | 17991720 | Both peroxisome proliferator-activated receptor-alpha (PPARalpha) and pancreatic/duodenal homeobox-1 (PDX-1) have been reported to be associated with glucose-stimulated insulin secretion (GSIS), but the relationship between PPARalpha and PDX-1 is not yet fully understood. |
| 2816 | 17991720 | In the present study, we tested the hypothesis that PPARalpha regulates the expression of PDX-1 in beta-cells. |
| 2817 | 17991720 | In turn, this enhanced expression led to an increase in PDX-1 mRNA and nuclear protein, as well as DNA binding activity of PDX-1 with the insulin promoter. |
| 2818 | 17991720 | Accordingly, the expression of the PDX-1 downstream targets, insulin and glucose transporter-2, increased, resulting in increased intracellular insulin content and GSIS. |
| 2819 | 17991720 | Treatment with MK886 inhibited expression of PPARalpha, blocking PPARalpha-regulated PDX-1 expression, and the downstream transcription events of PDX-1. |
| 2820 | 17991720 | Collectively, these results demonstrate a regulatory relationship between PPARalpha and PDX-1 in INS-1 cells. |
| 2821 | 17991720 | Furthermore, PPARalpha activation potentiates GSIS under elevated palmitate conditions possibly via up-regulation of PDX-1. |
| 2822 | 17991720 | Peroxisome proliferator-activated receptor-alpha regulates the expression of pancreatic/duodenal homeobox-1 in rat insulinoma (INS-1) cells and ameliorates glucose-induced insulin secretion impaired by palmitate. |
| 2823 | 17991720 | Both peroxisome proliferator-activated receptor-alpha (PPARalpha) and pancreatic/duodenal homeobox-1 (PDX-1) have been reported to be associated with glucose-stimulated insulin secretion (GSIS), but the relationship between PPARalpha and PDX-1 is not yet fully understood. |
| 2824 | 17991720 | In the present study, we tested the hypothesis that PPARalpha regulates the expression of PDX-1 in beta-cells. |
| 2825 | 17991720 | In turn, this enhanced expression led to an increase in PDX-1 mRNA and nuclear protein, as well as DNA binding activity of PDX-1 with the insulin promoter. |
| 2826 | 17991720 | Accordingly, the expression of the PDX-1 downstream targets, insulin and glucose transporter-2, increased, resulting in increased intracellular insulin content and GSIS. |
| 2827 | 17991720 | Treatment with MK886 inhibited expression of PPARalpha, blocking PPARalpha-regulated PDX-1 expression, and the downstream transcription events of PDX-1. |
| 2828 | 17991720 | Collectively, these results demonstrate a regulatory relationship between PPARalpha and PDX-1 in INS-1 cells. |
| 2829 | 17991720 | Furthermore, PPARalpha activation potentiates GSIS under elevated palmitate conditions possibly via up-regulation of PDX-1. |
| 2830 | 17991720 | Peroxisome proliferator-activated receptor-alpha regulates the expression of pancreatic/duodenal homeobox-1 in rat insulinoma (INS-1) cells and ameliorates glucose-induced insulin secretion impaired by palmitate. |
| 2831 | 17991720 | Both peroxisome proliferator-activated receptor-alpha (PPARalpha) and pancreatic/duodenal homeobox-1 (PDX-1) have been reported to be associated with glucose-stimulated insulin secretion (GSIS), but the relationship between PPARalpha and PDX-1 is not yet fully understood. |
| 2832 | 17991720 | In the present study, we tested the hypothesis that PPARalpha regulates the expression of PDX-1 in beta-cells. |
| 2833 | 17991720 | In turn, this enhanced expression led to an increase in PDX-1 mRNA and nuclear protein, as well as DNA binding activity of PDX-1 with the insulin promoter. |
| 2834 | 17991720 | Accordingly, the expression of the PDX-1 downstream targets, insulin and glucose transporter-2, increased, resulting in increased intracellular insulin content and GSIS. |
| 2835 | 17991720 | Treatment with MK886 inhibited expression of PPARalpha, blocking PPARalpha-regulated PDX-1 expression, and the downstream transcription events of PDX-1. |
| 2836 | 17991720 | Collectively, these results demonstrate a regulatory relationship between PPARalpha and PDX-1 in INS-1 cells. |
| 2837 | 17991720 | Furthermore, PPARalpha activation potentiates GSIS under elevated palmitate conditions possibly via up-regulation of PDX-1. |
| 2838 | 17991758 | Cyclical and alternating infusions of glucose and intralipid in rats inhibit insulin gene expression and Pdx-1 binding in islets. |
| 2839 | 17996499 | Expression of HNF-4alpha (MODY1), HNF-1beta (MODY5), and HNF-1alpha (MODY3) proteins in the developing mouse pancreas. |
| 2840 | 17996499 | The type 1, 3, and 5 forms of maturity-onset diabetes of the young (MODY) are caused by mutations of the genes encoding hepatocyte nuclear factor (HNF)-4alpha, HNF-1alpha, and HNF-1beta, respectively [Yamagata, K., Oda, N., Kaisaki, P.J., Menzel, S., Furuta, H., Vaxillaire, M., et al., 1996a. |
| 2841 | 17996499 | Mutation in hepatocyte nuclear factor-1beta gene (TCF2) associated with MODY. |
| 2842 | 17996499 | We performed an immunohistochemical study to investigate its expression in comparison with the expression of HNF-1alpha and HNF-1beta. |
| 2843 | 17996499 | HNF-4alpha and HNF-1beta were initially expressed by Pdx1(+) common progenitor cells and neurogenin3(+) (Ngn3(+)) endocrine precursor cells during the first transition, but expression of HNF-1beta and either HNF-4alpha or HNF-1alpha became complementary around the end of the second transition (E15.5). |
| 2844 | 17996499 | In the mature pancreas, HNF-4alpha was expressed by glucagon-positive alpha-cells, insulin-positive beta-cells, somatostatin-positive delta-cells, and pancreatic polypeptide-positive PP-cells, as well as by pancreatic exocrine cells and ductal cells. |
| 2845 | 17996499 | Most of the HNF-4alpha(+) cells were also positive for HNF-1alpha, but HNF-4alpha expression in some non-beta-cells was remarkably high, and this was not paralleled by high HNF-1alpha expression. |
| 2846 | 18029451 | Unexpectedly expression of Irs2 and the downstream gene Pdx1 were unaffected. |
| 2847 | 18037333 | In particular, we examined and characterized the expression of several stem cell (nestin, ABCG2, c-kit), growth and differentiation markers (GLP-1R, c-met, erbB1), and PDZD2 in PPCs by RT-PCR, Western blot, and immunocytochemistry. |
| 2848 | 18037333 | PDZD2 and sPDZD2 were detected at high levels in both human fetal pancreas and in PPCs. sPDZD2 acted as a potent mitogen on PPCs, and inhibited the differentiation of PPC-derived islet-like cell-clusters (ICCs), evidenced by the downregulation of Isl-1, Pdx-1, and insulin mRNA levels. sPDZD2 treatment also reduced levels of C-peptide in ICCs. |
| 2849 | 18060872 | Betacellulin and nicotinamide sustain PDX1 expression and induce pancreatic beta-cell differentiation in human embryonic stem cells. |
| 2850 | 18060872 | The addition of betacellulin and nicotinamide sustained PDX1 expression and induced beta-cell differentiation. |
| 2851 | 18060872 | Betacellulin and nicotinamide sustain PDX1 expression and induce pancreatic beta-cell differentiation in human embryonic stem cells. |
| 2852 | 18060872 | The addition of betacellulin and nicotinamide sustained PDX1 expression and induced beta-cell differentiation. |
| 2853 | 18155663 | We demonstrated that RZG beneficial effects on insulin secretion and apoptosis did not imply PDX-1 or insulin gene modulation. |
| 2854 | 18180315 | Pancreatic duodenal homeobox 1 (PDX1), forkhead box transcription factor a2 (Foxa2), glucokinase, pancreatic polypeptide and low-level insulin gene transcription in wild-type AR42J cells were confirmed by RT-PCR. |
| 2855 | 18180315 | Culture on Matrigel-coated plates and supplementation of medium with glucagon-like peptide 1 induced expression of the beta-cell Glut 2 with maintained expression of insulin and PDX1. |
| 2856 | 18180315 | Pancreatic duodenal homeobox 1 (PDX1), forkhead box transcription factor a2 (Foxa2), glucokinase, pancreatic polypeptide and low-level insulin gene transcription in wild-type AR42J cells were confirmed by RT-PCR. |
| 2857 | 18180315 | Culture on Matrigel-coated plates and supplementation of medium with glucagon-like peptide 1 induced expression of the beta-cell Glut 2 with maintained expression of insulin and PDX1. |
| 2858 | 18199433 | During pancreatic development insulin(+) cells co-express the transcription factors MafB and Pax6, and transition from a MafA(-) to MafA(+) state. |
| 2859 | 18199433 | To examine the role of Pax6 and MafB in the development of beta-cells, we analyzed embryonic pancreata from Pax6- and MafB-deficient mice. |
| 2860 | 18199433 | Pax6 deficiency, as manifest in the Pax6(Sey-Neu) allele, reduced not only the number of cells expressing insulin or glucagon, but also the number of MafB, PDX-1 and MafA expressing cells. |
| 2861 | 18199433 | We show that MafB can directly activate expression of insulin and glucagon, and a MafB protein engineered to contain N248S mutation in the MafB (kr(ENU)) results in significantly reduced activation. |
| 2862 | 18199433 | Furthermore, pancreata from MafB deficient (kr(ENU)/kr(ENU)) mice exhibited reduced number of cells expressing insulin, glucagon, PDX-1 and MafA, with only a minor reduction in MafB expressing cells. |
| 2863 | 18199433 | Similar to Pax6 deficient mice, MafB deficient mice showed reductions both in insulin and glucagon expressing cells and in the ability of MafB and PDX-1 expressing cells to activate expression of these hormones. |
| 2864 | 18199433 | These results suggest that MafB may function as a downstream mediator of Pax6 in regulating the specification of insulin and glucagon expressing cells. |
| 2865 | 18199433 | Interestingly, the remaining insulin(+) cells in these knockouts preferentially express Hb9, suggesting the existence of an alternate pathway for the generation of insulin expressing cells, even in the absence of Pax6 and MafB function. |
| 2866 | 18199433 | Thus, Pax6 acts upstream of MafB, which in turn may trigger the expression of insulin and regulate the PDX-1 and MafA expression required for beta-cell maturation. |
| 2867 | 18199433 | During pancreatic development insulin(+) cells co-express the transcription factors MafB and Pax6, and transition from a MafA(-) to MafA(+) state. |
| 2868 | 18199433 | To examine the role of Pax6 and MafB in the development of beta-cells, we analyzed embryonic pancreata from Pax6- and MafB-deficient mice. |
| 2869 | 18199433 | Pax6 deficiency, as manifest in the Pax6(Sey-Neu) allele, reduced not only the number of cells expressing insulin or glucagon, but also the number of MafB, PDX-1 and MafA expressing cells. |
| 2870 | 18199433 | We show that MafB can directly activate expression of insulin and glucagon, and a MafB protein engineered to contain N248S mutation in the MafB (kr(ENU)) results in significantly reduced activation. |
| 2871 | 18199433 | Furthermore, pancreata from MafB deficient (kr(ENU)/kr(ENU)) mice exhibited reduced number of cells expressing insulin, glucagon, PDX-1 and MafA, with only a minor reduction in MafB expressing cells. |
| 2872 | 18199433 | Similar to Pax6 deficient mice, MafB deficient mice showed reductions both in insulin and glucagon expressing cells and in the ability of MafB and PDX-1 expressing cells to activate expression of these hormones. |
| 2873 | 18199433 | These results suggest that MafB may function as a downstream mediator of Pax6 in regulating the specification of insulin and glucagon expressing cells. |
| 2874 | 18199433 | Interestingly, the remaining insulin(+) cells in these knockouts preferentially express Hb9, suggesting the existence of an alternate pathway for the generation of insulin expressing cells, even in the absence of Pax6 and MafB function. |
| 2875 | 18199433 | Thus, Pax6 acts upstream of MafB, which in turn may trigger the expression of insulin and regulate the PDX-1 and MafA expression required for beta-cell maturation. |
| 2876 | 18199433 | During pancreatic development insulin(+) cells co-express the transcription factors MafB and Pax6, and transition from a MafA(-) to MafA(+) state. |
| 2877 | 18199433 | To examine the role of Pax6 and MafB in the development of beta-cells, we analyzed embryonic pancreata from Pax6- and MafB-deficient mice. |
| 2878 | 18199433 | Pax6 deficiency, as manifest in the Pax6(Sey-Neu) allele, reduced not only the number of cells expressing insulin or glucagon, but also the number of MafB, PDX-1 and MafA expressing cells. |
| 2879 | 18199433 | We show that MafB can directly activate expression of insulin and glucagon, and a MafB protein engineered to contain N248S mutation in the MafB (kr(ENU)) results in significantly reduced activation. |
| 2880 | 18199433 | Furthermore, pancreata from MafB deficient (kr(ENU)/kr(ENU)) mice exhibited reduced number of cells expressing insulin, glucagon, PDX-1 and MafA, with only a minor reduction in MafB expressing cells. |
| 2881 | 18199433 | Similar to Pax6 deficient mice, MafB deficient mice showed reductions both in insulin and glucagon expressing cells and in the ability of MafB and PDX-1 expressing cells to activate expression of these hormones. |
| 2882 | 18199433 | These results suggest that MafB may function as a downstream mediator of Pax6 in regulating the specification of insulin and glucagon expressing cells. |
| 2883 | 18199433 | Interestingly, the remaining insulin(+) cells in these knockouts preferentially express Hb9, suggesting the existence of an alternate pathway for the generation of insulin expressing cells, even in the absence of Pax6 and MafB function. |
| 2884 | 18199433 | Thus, Pax6 acts upstream of MafB, which in turn may trigger the expression of insulin and regulate the PDX-1 and MafA expression required for beta-cell maturation. |
| 2885 | 18199433 | During pancreatic development insulin(+) cells co-express the transcription factors MafB and Pax6, and transition from a MafA(-) to MafA(+) state. |
| 2886 | 18199433 | To examine the role of Pax6 and MafB in the development of beta-cells, we analyzed embryonic pancreata from Pax6- and MafB-deficient mice. |
| 2887 | 18199433 | Pax6 deficiency, as manifest in the Pax6(Sey-Neu) allele, reduced not only the number of cells expressing insulin or glucagon, but also the number of MafB, PDX-1 and MafA expressing cells. |
| 2888 | 18199433 | We show that MafB can directly activate expression of insulin and glucagon, and a MafB protein engineered to contain N248S mutation in the MafB (kr(ENU)) results in significantly reduced activation. |
| 2889 | 18199433 | Furthermore, pancreata from MafB deficient (kr(ENU)/kr(ENU)) mice exhibited reduced number of cells expressing insulin, glucagon, PDX-1 and MafA, with only a minor reduction in MafB expressing cells. |
| 2890 | 18199433 | Similar to Pax6 deficient mice, MafB deficient mice showed reductions both in insulin and glucagon expressing cells and in the ability of MafB and PDX-1 expressing cells to activate expression of these hormones. |
| 2891 | 18199433 | These results suggest that MafB may function as a downstream mediator of Pax6 in regulating the specification of insulin and glucagon expressing cells. |
| 2892 | 18199433 | Interestingly, the remaining insulin(+) cells in these knockouts preferentially express Hb9, suggesting the existence of an alternate pathway for the generation of insulin expressing cells, even in the absence of Pax6 and MafB function. |
| 2893 | 18199433 | Thus, Pax6 acts upstream of MafB, which in turn may trigger the expression of insulin and regulate the PDX-1 and MafA expression required for beta-cell maturation. |
| 2894 | 18220583 | Oxidative stress and/or activation of the JNK pathway suppress insulin gene expression, accompanied by reduction of PDX-1 DNA binding activity. |
| 2895 | 18220583 | The JNK pathway is also involved in the progression of insulin resistance; suppression of the JNK pathway in obese diabetic mice markedly improves insulin resistance and ameliorates glucose tolerance. |
| 2896 | 18220583 | The phosphorylation state of key molecules for insulin signaling is altered upon modification of the JNK pathway. |
| 2897 | 18220583 | Taken together, the JNK pathway plays a crucial role in progression of insulin resistance as well as beta-cell dysfunction found in diabetes and thus could be a potential therapeutic target for diabetes. |
| 2898 | 18253862 | This study was conducted to evaluate whether pdx-1 gene delivered by adeno-associated virus (AAV) could induce autologous liver cells to differentiate into insulin-producing cells and to explore the origin of these cells. |
| 2899 | 18253862 | Here we used 4 x 10e(11) AAV to deliver pdx-1 to STZ-induced diabetic rats via the portal vein. |
| 2900 | 18253862 | Immunofluorescent staining showed more insulin-positive cells, which had similar morphology with hepatic oval stem cells and were positive for hepatic oval stem cell markers, Thy-1 and cytokeratin 19 (ck19). |
| 2901 | 18253862 | Our data indicated that rat hepatic oval stem cells were differentiated into bioactive insulin-producing cells by AAV-pdx-1 delivery in diabetic rats, with promoted expression of some transcription factors necessary for beta cell development and function. |
| 2902 | 18253862 | This study was conducted to evaluate whether pdx-1 gene delivered by adeno-associated virus (AAV) could induce autologous liver cells to differentiate into insulin-producing cells and to explore the origin of these cells. |
| 2903 | 18253862 | Here we used 4 x 10e(11) AAV to deliver pdx-1 to STZ-induced diabetic rats via the portal vein. |
| 2904 | 18253862 | Immunofluorescent staining showed more insulin-positive cells, which had similar morphology with hepatic oval stem cells and were positive for hepatic oval stem cell markers, Thy-1 and cytokeratin 19 (ck19). |
| 2905 | 18253862 | Our data indicated that rat hepatic oval stem cells were differentiated into bioactive insulin-producing cells by AAV-pdx-1 delivery in diabetic rats, with promoted expression of some transcription factors necessary for beta cell development and function. |
| 2906 | 18253862 | This study was conducted to evaluate whether pdx-1 gene delivered by adeno-associated virus (AAV) could induce autologous liver cells to differentiate into insulin-producing cells and to explore the origin of these cells. |
| 2907 | 18253862 | Here we used 4 x 10e(11) AAV to deliver pdx-1 to STZ-induced diabetic rats via the portal vein. |
| 2908 | 18253862 | Immunofluorescent staining showed more insulin-positive cells, which had similar morphology with hepatic oval stem cells and were positive for hepatic oval stem cell markers, Thy-1 and cytokeratin 19 (ck19). |
| 2909 | 18253862 | Our data indicated that rat hepatic oval stem cells were differentiated into bioactive insulin-producing cells by AAV-pdx-1 delivery in diabetic rats, with promoted expression of some transcription factors necessary for beta cell development and function. |
| 2910 | 18288891 | Insulin resistance is characterized by impaired signaling through the insulin/insulin receptor/insulin receptor substrate/PI-3K/Akt pathway, leading to elevation of negatively regulated substrates such as glycogen synthase kinase-3beta (Gsk-3beta). |
| 2911 | 18288891 | In these studies, we designed experiments to determine the contribution of Gsk-3beta to regulation of beta-cell mass in two mouse models of insulin resistance. |
| 2912 | 18288891 | Crossing these mice with those having haploinsufficiency for Gsk-3beta (Gsk-3beta+/-) reduced insulin resistance by augmenting whole-body glucose disposal, and significantly reduced beta-cell mass. |
| 2913 | 18288891 | Preservation of beta-cell mass in Gsk-3beta+/- Irs2-/- mice was accompanied by suppressed p27(kip1) levels and increased Pdx1 levels. |
| 2914 | 18288891 | To separate peripheral versus beta-cell-specific effects of reduction of Gsk3beta activity on preservation of beta-cell mass, mice homozygous for a floxed Gsk-3beta allele (Gsk-3(F/F)) were then crossed with rat insulin promoter-Cre (RIP-Cre) mice to produce beta-cell-specific knockout of Gsk-3beta (betaGsk-3beta-/-). |
| 2915 | 18338074 | In mature beta-cells, PDX-1 transactivates insulin and other beta-cell-related genes such as GLUT2 and glucokinase. |
| 2916 | 18338074 | Furthermore, PDX-1 plays an important role in the induction of insulin-producing cells in various non-beta-cells and is thereby a possible therapeutic target for diabetes. |
| 2917 | 18338074 | On the other hand, under diabetic conditions, expression and/or activity of PDX-1 in beta-cells is reduced, which leads to suppression of insulin biosynthesis and secretion. |
| 2918 | 18338074 | In mature beta-cells, PDX-1 transactivates insulin and other beta-cell-related genes such as GLUT2 and glucokinase. |
| 2919 | 18338074 | Furthermore, PDX-1 plays an important role in the induction of insulin-producing cells in various non-beta-cells and is thereby a possible therapeutic target for diabetes. |
| 2920 | 18338074 | On the other hand, under diabetic conditions, expression and/or activity of PDX-1 in beta-cells is reduced, which leads to suppression of insulin biosynthesis and secretion. |
| 2921 | 18338074 | In mature beta-cells, PDX-1 transactivates insulin and other beta-cell-related genes such as GLUT2 and glucokinase. |
| 2922 | 18338074 | Furthermore, PDX-1 plays an important role in the induction of insulin-producing cells in various non-beta-cells and is thereby a possible therapeutic target for diabetes. |
| 2923 | 18338074 | On the other hand, under diabetic conditions, expression and/or activity of PDX-1 in beta-cells is reduced, which leads to suppression of insulin biosynthesis and secretion. |
| 2924 | 18360684 | The participation of pancreatic duodenal homeobox factor-1 (PDX-1) in the transcription of several genes which are essential for glucose sensing and insulin synthesis underlines its key role in beta-cells of the pancreas. |
| 2925 | 18360684 | PDX-1 binds to the promoter of insulin, glucose transporter 2, and glucokinase and regulates their expression. |
| 2926 | 18360684 | By protein-protein interaction, PDX-1 acts in concert with other transcription factors or coactivators at the level of the insulin promoter. |
| 2927 | 18360684 | The participation of pancreatic duodenal homeobox factor-1 (PDX-1) in the transcription of several genes which are essential for glucose sensing and insulin synthesis underlines its key role in beta-cells of the pancreas. |
| 2928 | 18360684 | PDX-1 binds to the promoter of insulin, glucose transporter 2, and glucokinase and regulates their expression. |
| 2929 | 18360684 | By protein-protein interaction, PDX-1 acts in concert with other transcription factors or coactivators at the level of the insulin promoter. |
| 2930 | 18360684 | The participation of pancreatic duodenal homeobox factor-1 (PDX-1) in the transcription of several genes which are essential for glucose sensing and insulin synthesis underlines its key role in beta-cells of the pancreas. |
| 2931 | 18360684 | PDX-1 binds to the promoter of insulin, glucose transporter 2, and glucokinase and regulates their expression. |
| 2932 | 18360684 | By protein-protein interaction, PDX-1 acts in concert with other transcription factors or coactivators at the level of the insulin promoter. |
| 2933 | 18406800 | Homeodomain protein IDX-1: a master regulator of pancreas development and insulin gene expression. |
| 2934 | 18406800 | In the adult endocrine pancreas, IDX-1 is primarily expressed in beta cells, where it is a key factor in the upregulation of insulin gene transcription and appears to have a role in the regulation of the somatostatin, glucokinase, glucose transporter-2, and islet amyloid polypeptide genes. |
| 2935 | 18406800 | The observed functions of IDX-1 and its downregulation in parallel with insulin in glucose-toxicity models implicate IDX-1 as a potential factor contributing to the pathogenesis of diabetes mellitus. |
| 2936 | 18406800 | Homeodomain protein IDX-1: a master regulator of pancreas development and insulin gene expression. |
| 2937 | 18406800 | In the adult endocrine pancreas, IDX-1 is primarily expressed in beta cells, where it is a key factor in the upregulation of insulin gene transcription and appears to have a role in the regulation of the somatostatin, glucokinase, glucose transporter-2, and islet amyloid polypeptide genes. |
| 2938 | 18406800 | The observed functions of IDX-1 and its downregulation in parallel with insulin in glucose-toxicity models implicate IDX-1 as a potential factor contributing to the pathogenesis of diabetes mellitus. |
| 2939 | 18406800 | Homeodomain protein IDX-1: a master regulator of pancreas development and insulin gene expression. |
| 2940 | 18406800 | In the adult endocrine pancreas, IDX-1 is primarily expressed in beta cells, where it is a key factor in the upregulation of insulin gene transcription and appears to have a role in the regulation of the somatostatin, glucokinase, glucose transporter-2, and islet amyloid polypeptide genes. |
| 2941 | 18406800 | The observed functions of IDX-1 and its downregulation in parallel with insulin in glucose-toxicity models implicate IDX-1 as a potential factor contributing to the pathogenesis of diabetes mellitus. |
| 2942 | 18420028 | BrdU(+) insulin(-) PDX-1(+) cells, Ngn3(+) cells and insulin(+) glucagon(+) cells, which showed stem cells, were also found during beta-cell regeneration. |
| 2943 | 18420028 | In recipient pancreas, transplanted cells simultaneously expressed CD34 but did not express insulin, PDX-1, Ngn3, Nkx2.2, Nkx6.1, Pax4, Pax6, and CD45. |
| 2944 | 18420028 | BrdU(+) insulin(-) PDX-1(+) cells, Ngn3(+) cells and insulin(+) glucagon(+) cells, which showed stem cells, were also found during beta-cell regeneration. |
| 2945 | 18420028 | In recipient pancreas, transplanted cells simultaneously expressed CD34 but did not express insulin, PDX-1, Ngn3, Nkx2.2, Nkx6.1, Pax4, Pax6, and CD45. |
| 2946 | 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. |
| 2947 | 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. |
| 2948 | 18450959 | We examined whether ER stress decreases insulin gene expression, and this process is mediated by ATF6. |
| 2949 | 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. |
| 2950 | 18450959 | ATF6 inhibited insulin promoter activity, whereas X-box binding protein-1 and ATF4 did not. |
| 2951 | 18450959 | Adenovirus-mediated overexpression of active form of ATF6 in INS-1 cells impaired insulin gene expression and secretion. |
| 2952 | 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. |
| 2953 | 18450959 | The ATF6-induced suppression of insulin gene expression was associated with up-regulation of SHP gene expression. |
| 2954 | 18464933 | The fetal IUGR state was characterized by loss of USF-1 binding at the proximal promoter of Pdx1, recruitment of the histone deacetylase 1 (HDAC1) and the corepressor Sin3A, and deacetylation of histones H3 and H4. |
| 2955 | 18464933 | During the neonatal period, these epigenetic changes and the reduction in Pdx1 expression could be reversed by HDAC inhibition. |
| 2956 | 18464933 | The fetal IUGR state was characterized by loss of USF-1 binding at the proximal promoter of Pdx1, recruitment of the histone deacetylase 1 (HDAC1) and the corepressor Sin3A, and deacetylation of histones H3 and H4. |
| 2957 | 18464933 | During the neonatal period, these epigenetic changes and the reduction in Pdx1 expression could be reversed by HDAC inhibition. |
| 2958 | 18468239 | A previous study reported that exogenous PDX-1 protein can be transduced into pancreatic stem/progenitor cells and induce differentiation of the cells into insulin-producing cells without requiring gene transfer technology. |
| 2959 | 18468239 | Cell treatment with heparinase-III demonstrated impaired PDX-1 internalization, while treatment with chondroitinase ABC, or with chondroitinase AC, was completely ineffective in inhibiting PDX-1 internalization. |
| 2960 | 18468239 | These data indicate that cell-surface heparan sulfate proteoglycans are required for PDX-1 internalization and that PDX-1 protein transduction could be a valuable strategy for inducing insulin expression in pancreatic stem/progenitor cells without requiring gene transfer technology. |
| 2961 | 18468239 | A previous study reported that exogenous PDX-1 protein can be transduced into pancreatic stem/progenitor cells and induce differentiation of the cells into insulin-producing cells without requiring gene transfer technology. |
| 2962 | 18468239 | Cell treatment with heparinase-III demonstrated impaired PDX-1 internalization, while treatment with chondroitinase ABC, or with chondroitinase AC, was completely ineffective in inhibiting PDX-1 internalization. |
| 2963 | 18468239 | These data indicate that cell-surface heparan sulfate proteoglycans are required for PDX-1 internalization and that PDX-1 protein transduction could be a valuable strategy for inducing insulin expression in pancreatic stem/progenitor cells without requiring gene transfer technology. |
| 2964 | 18468239 | A previous study reported that exogenous PDX-1 protein can be transduced into pancreatic stem/progenitor cells and induce differentiation of the cells into insulin-producing cells without requiring gene transfer technology. |
| 2965 | 18468239 | Cell treatment with heparinase-III demonstrated impaired PDX-1 internalization, while treatment with chondroitinase ABC, or with chondroitinase AC, was completely ineffective in inhibiting PDX-1 internalization. |
| 2966 | 18468239 | These data indicate that cell-surface heparan sulfate proteoglycans are required for PDX-1 internalization and that PDX-1 protein transduction could be a valuable strategy for inducing insulin expression in pancreatic stem/progenitor cells without requiring gene transfer technology. |
| 2967 | 18506375 | The Chi-square test, multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of hypertension, hypercholesterolemia, and diabetes mellitus, as well as a stepwise forward selection procedure revealed that the 2445G-->A (Ala54Thr) polymorphism (rs1799883) of FABP2, the -108/3G-->4G polymorphism of IPF1 (S82168), the A-->G (Thr94Ala) polymorphism (rs2241883) of FABP1, the G-->A (Asp2213Asn) polymorphism (rs529038) of ROS1, the -11377C-->G polymorphism (rs266729) of ADIPOQ, the 162A-->C polymorphism (rs4769055) of ALOX5AP, the -786T-->C polymorphism (rs2070744) of NOS3, and the 3279C-->T polymorphism (rs7291467) of LGALS2 were associated (P<0.05) with the prevalence of atherothrombotic cerebral infarction. |
| 2968 | 18506375 | Our results suggest that FABP2, IPF1, FABP1, ROS1, ADIPOQ, ALOX5AP, NOS3, and LGALS2 are susceptibility loci for atherothrombotic cerebral infarction among Japanese individuals with metabolic syndrome. |
| 2969 | 18512226 | We sequenced genes with a recognized role in monogenic forms of diabetes, including KCNJ11, ABCC8, GCK, IPF1, HNF1beta, NeuroD1 and TCF7L2, as well as a novel candidate gene, HNF6, known to be involved in hepatobiliary and pancreatic development, but did not identify mutations. |
| 2970 | 18514140 | These clusters appeared about 9 days after pancreatic differentiation; expressed pancreatic beta-cell markers, including insulin, glucagon, Glut-2, PDX1, Pax4, and Ngn3; and could synthesize and secrete functional islet proteins at the end of the inducing protocol. |
| 2971 | 18535489 | At 6 wk of development (wd) insulin promoting factor 1 (IPF1) was expressed in the majority of epithelial cells forming tubular structures while GR was present in the mesenchyme, suggesting an early role of glucocorticoids, before endocrine and exocrine differentiation. |
| 2972 | 18535489 | The first insulin cells did not express IPF1 or GR. |
| 2973 | 18535489 | Islet formation occurred from 10 wd as IPF1-positive cells started to express simultaneously insulin and GR. |
| 2974 | 18535489 | At 6 wk of development (wd) insulin promoting factor 1 (IPF1) was expressed in the majority of epithelial cells forming tubular structures while GR was present in the mesenchyme, suggesting an early role of glucocorticoids, before endocrine and exocrine differentiation. |
| 2975 | 18535489 | The first insulin cells did not express IPF1 or GR. |
| 2976 | 18535489 | Islet formation occurred from 10 wd as IPF1-positive cells started to express simultaneously insulin and GR. |
| 2977 | 18535489 | At 6 wk of development (wd) insulin promoting factor 1 (IPF1) was expressed in the majority of epithelial cells forming tubular structures while GR was present in the mesenchyme, suggesting an early role of glucocorticoids, before endocrine and exocrine differentiation. |
| 2978 | 18535489 | The first insulin cells did not express IPF1 or GR. |
| 2979 | 18535489 | Islet formation occurred from 10 wd as IPF1-positive cells started to express simultaneously insulin and GR. |
| 2980 | 18593820 | The present study was undertaken to determine how tumour necrosis factor-alpha (TNF-alpha) elicits the inhibition of glucose-stimulated insulin secretion (GSIS) in rat insulinoma cells (INS)-1 beta-cells. |
| 2981 | 18593820 | TNF-alpha pretreatment did not change the expression levels of insulin, PDX-1, glucose transporter 2, glucokinase, K(ATP) channels, Ca(2)(+) channels, and exocytotic molecules and, furthermore, did not reduce the glucose-stimulated ATP level. |
| 2982 | 18593820 | The TNF-alpha treatment was thought to activate c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and NF-kappaB inflammatory signals, since TNF-alpha increased phospho-JNK and phospho-p38 and reduced I kappaB levels. |
| 2983 | 18593820 | Overexpression of MEKK3, a possible mediator from the TNF-alpha receptor to the JNK/p38 and NK-kappaB signaling cascade, increased the levels of phospho-JNK, phospho-p38, and NF-kappaB, and reduced the glucose-stimulated Ca(2)(+) influx and GSIS. |
| 2984 | 18593820 | The reduction of the Ca(2)(+) influx and GSIS in MEKK3-overexpressing INS-1 cells was also prevented by inhibitors of JNK, p38, and NF-kappaB. |
| 2985 | 18593820 | These data demonstrate that TNF-alpha inhibits GSIS by reducing the glucose-stimulated Ca(2)(+) influx, possibly through the activation of JNK and p38 MAPK and NF-kappaB inflammatory signals. |
| 2986 | 18593849 | Pax6 and Pdx1 are required for production of glucose-dependent insulinotropic polypeptide in proglucagon-expressing L cells. |
| 2987 | 18593849 | Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are incretin hormones that play important roles in maintaining glucose homeostasis and are being actively pursued as novel therapeutic agents for diabetes. |
| 2988 | 18593849 | GIP is produced by dispersed enteroendocrine cells and interestingly at times is coexpressed with GLP-1. |
| 2989 | 18593849 | We performed comparative immunostaining of Pax6 and Pdx1 in GIP- and GLP-1-secreting cells. |
| 2990 | 18593849 | We investigated whether Pax6 and Pdx1 activate the human GIP promoter in control IEC-6 cells and GIP-expressing STC-1 cells. |
| 2991 | 18593849 | Pax6 and Pdx1 consistently colocalized in GIP-immunoreactive cells. |
| 2992 | 18593849 | Cells that coexpress GIP and GLP-1 were Pax6 and Pdx1 positive, whereas cells expressing only GLP-1 were Pax6 positive but did not express Pdx1. |
| 2993 | 18593849 | GIP promoter activity was enhanced in IEC-6 cells by exogenous Pax6 or Pdx1 and diminished in STC-1 cells by inhibition of endogenous Pax6 or Pdx1 by dominant-negative forms. |
| 2994 | 18593849 | EMSA studies indicated that Pax6 and Pdx1 bind to this proximal sequence of the human GIP promoter. |
| 2995 | 18593849 | Our findings indicate that concomitant expression of Pax6 and Pdx1 is important for GIP expression. |
| 2996 | 18593849 | Our results also suggest that the presence of Pdx1 defines whether GLP-1-expressing gastrointestinal L cells also coexpress GIP. |
| 2997 | 18593849 | Pax6 and Pdx1 are required for production of glucose-dependent insulinotropic polypeptide in proglucagon-expressing L cells. |
| 2998 | 18593849 | Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are incretin hormones that play important roles in maintaining glucose homeostasis and are being actively pursued as novel therapeutic agents for diabetes. |
| 2999 | 18593849 | GIP is produced by dispersed enteroendocrine cells and interestingly at times is coexpressed with GLP-1. |
| 3000 | 18593849 | We performed comparative immunostaining of Pax6 and Pdx1 in GIP- and GLP-1-secreting cells. |
| 3001 | 18593849 | We investigated whether Pax6 and Pdx1 activate the human GIP promoter in control IEC-6 cells and GIP-expressing STC-1 cells. |
| 3002 | 18593849 | Pax6 and Pdx1 consistently colocalized in GIP-immunoreactive cells. |
| 3003 | 18593849 | Cells that coexpress GIP and GLP-1 were Pax6 and Pdx1 positive, whereas cells expressing only GLP-1 were Pax6 positive but did not express Pdx1. |
| 3004 | 18593849 | GIP promoter activity was enhanced in IEC-6 cells by exogenous Pax6 or Pdx1 and diminished in STC-1 cells by inhibition of endogenous Pax6 or Pdx1 by dominant-negative forms. |
| 3005 | 18593849 | EMSA studies indicated that Pax6 and Pdx1 bind to this proximal sequence of the human GIP promoter. |
| 3006 | 18593849 | Our findings indicate that concomitant expression of Pax6 and Pdx1 is important for GIP expression. |
| 3007 | 18593849 | Our results also suggest that the presence of Pdx1 defines whether GLP-1-expressing gastrointestinal L cells also coexpress GIP. |
| 3008 | 18593849 | Pax6 and Pdx1 are required for production of glucose-dependent insulinotropic polypeptide in proglucagon-expressing L cells. |
| 3009 | 18593849 | Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are incretin hormones that play important roles in maintaining glucose homeostasis and are being actively pursued as novel therapeutic agents for diabetes. |
| 3010 | 18593849 | GIP is produced by dispersed enteroendocrine cells and interestingly at times is coexpressed with GLP-1. |
| 3011 | 18593849 | We performed comparative immunostaining of Pax6 and Pdx1 in GIP- and GLP-1-secreting cells. |
| 3012 | 18593849 | We investigated whether Pax6 and Pdx1 activate the human GIP promoter in control IEC-6 cells and GIP-expressing STC-1 cells. |
| 3013 | 18593849 | Pax6 and Pdx1 consistently colocalized in GIP-immunoreactive cells. |
| 3014 | 18593849 | Cells that coexpress GIP and GLP-1 were Pax6 and Pdx1 positive, whereas cells expressing only GLP-1 were Pax6 positive but did not express Pdx1. |
| 3015 | 18593849 | GIP promoter activity was enhanced in IEC-6 cells by exogenous Pax6 or Pdx1 and diminished in STC-1 cells by inhibition of endogenous Pax6 or Pdx1 by dominant-negative forms. |
| 3016 | 18593849 | EMSA studies indicated that Pax6 and Pdx1 bind to this proximal sequence of the human GIP promoter. |
| 3017 | 18593849 | Our findings indicate that concomitant expression of Pax6 and Pdx1 is important for GIP expression. |
| 3018 | 18593849 | Our results also suggest that the presence of Pdx1 defines whether GLP-1-expressing gastrointestinal L cells also coexpress GIP. |
| 3019 | 18593849 | Pax6 and Pdx1 are required for production of glucose-dependent insulinotropic polypeptide in proglucagon-expressing L cells. |
| 3020 | 18593849 | Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are incretin hormones that play important roles in maintaining glucose homeostasis and are being actively pursued as novel therapeutic agents for diabetes. |
| 3021 | 18593849 | GIP is produced by dispersed enteroendocrine cells and interestingly at times is coexpressed with GLP-1. |
| 3022 | 18593849 | We performed comparative immunostaining of Pax6 and Pdx1 in GIP- and GLP-1-secreting cells. |
| 3023 | 18593849 | We investigated whether Pax6 and Pdx1 activate the human GIP promoter in control IEC-6 cells and GIP-expressing STC-1 cells. |
| 3024 | 18593849 | Pax6 and Pdx1 consistently colocalized in GIP-immunoreactive cells. |
| 3025 | 18593849 | Cells that coexpress GIP and GLP-1 were Pax6 and Pdx1 positive, whereas cells expressing only GLP-1 were Pax6 positive but did not express Pdx1. |
| 3026 | 18593849 | GIP promoter activity was enhanced in IEC-6 cells by exogenous Pax6 or Pdx1 and diminished in STC-1 cells by inhibition of endogenous Pax6 or Pdx1 by dominant-negative forms. |
| 3027 | 18593849 | EMSA studies indicated that Pax6 and Pdx1 bind to this proximal sequence of the human GIP promoter. |
| 3028 | 18593849 | Our findings indicate that concomitant expression of Pax6 and Pdx1 is important for GIP expression. |
| 3029 | 18593849 | Our results also suggest that the presence of Pdx1 defines whether GLP-1-expressing gastrointestinal L cells also coexpress GIP. |
| 3030 | 18593849 | Pax6 and Pdx1 are required for production of glucose-dependent insulinotropic polypeptide in proglucagon-expressing L cells. |
| 3031 | 18593849 | Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are incretin hormones that play important roles in maintaining glucose homeostasis and are being actively pursued as novel therapeutic agents for diabetes. |
| 3032 | 18593849 | GIP is produced by dispersed enteroendocrine cells and interestingly at times is coexpressed with GLP-1. |
| 3033 | 18593849 | We performed comparative immunostaining of Pax6 and Pdx1 in GIP- and GLP-1-secreting cells. |
| 3034 | 18593849 | We investigated whether Pax6 and Pdx1 activate the human GIP promoter in control IEC-6 cells and GIP-expressing STC-1 cells. |
| 3035 | 18593849 | Pax6 and Pdx1 consistently colocalized in GIP-immunoreactive cells. |
| 3036 | 18593849 | Cells that coexpress GIP and GLP-1 were Pax6 and Pdx1 positive, whereas cells expressing only GLP-1 were Pax6 positive but did not express Pdx1. |
| 3037 | 18593849 | GIP promoter activity was enhanced in IEC-6 cells by exogenous Pax6 or Pdx1 and diminished in STC-1 cells by inhibition of endogenous Pax6 or Pdx1 by dominant-negative forms. |
| 3038 | 18593849 | EMSA studies indicated that Pax6 and Pdx1 bind to this proximal sequence of the human GIP promoter. |
| 3039 | 18593849 | Our findings indicate that concomitant expression of Pax6 and Pdx1 is important for GIP expression. |
| 3040 | 18593849 | Our results also suggest that the presence of Pdx1 defines whether GLP-1-expressing gastrointestinal L cells also coexpress GIP. |
| 3041 | 18593849 | Pax6 and Pdx1 are required for production of glucose-dependent insulinotropic polypeptide in proglucagon-expressing L cells. |
| 3042 | 18593849 | Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are incretin hormones that play important roles in maintaining glucose homeostasis and are being actively pursued as novel therapeutic agents for diabetes. |
| 3043 | 18593849 | GIP is produced by dispersed enteroendocrine cells and interestingly at times is coexpressed with GLP-1. |
| 3044 | 18593849 | We performed comparative immunostaining of Pax6 and Pdx1 in GIP- and GLP-1-secreting cells. |
| 3045 | 18593849 | We investigated whether Pax6 and Pdx1 activate the human GIP promoter in control IEC-6 cells and GIP-expressing STC-1 cells. |
| 3046 | 18593849 | Pax6 and Pdx1 consistently colocalized in GIP-immunoreactive cells. |
| 3047 | 18593849 | Cells that coexpress GIP and GLP-1 were Pax6 and Pdx1 positive, whereas cells expressing only GLP-1 were Pax6 positive but did not express Pdx1. |
| 3048 | 18593849 | GIP promoter activity was enhanced in IEC-6 cells by exogenous Pax6 or Pdx1 and diminished in STC-1 cells by inhibition of endogenous Pax6 or Pdx1 by dominant-negative forms. |
| 3049 | 18593849 | EMSA studies indicated that Pax6 and Pdx1 bind to this proximal sequence of the human GIP promoter. |
| 3050 | 18593849 | Our findings indicate that concomitant expression of Pax6 and Pdx1 is important for GIP expression. |
| 3051 | 18593849 | Our results also suggest that the presence of Pdx1 defines whether GLP-1-expressing gastrointestinal L cells also coexpress GIP. |
| 3052 | 18593849 | Pax6 and Pdx1 are required for production of glucose-dependent insulinotropic polypeptide in proglucagon-expressing L cells. |
| 3053 | 18593849 | Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are incretin hormones that play important roles in maintaining glucose homeostasis and are being actively pursued as novel therapeutic agents for diabetes. |
| 3054 | 18593849 | GIP is produced by dispersed enteroendocrine cells and interestingly at times is coexpressed with GLP-1. |
| 3055 | 18593849 | We performed comparative immunostaining of Pax6 and Pdx1 in GIP- and GLP-1-secreting cells. |
| 3056 | 18593849 | We investigated whether Pax6 and Pdx1 activate the human GIP promoter in control IEC-6 cells and GIP-expressing STC-1 cells. |
| 3057 | 18593849 | Pax6 and Pdx1 consistently colocalized in GIP-immunoreactive cells. |
| 3058 | 18593849 | Cells that coexpress GIP and GLP-1 were Pax6 and Pdx1 positive, whereas cells expressing only GLP-1 were Pax6 positive but did not express Pdx1. |
| 3059 | 18593849 | GIP promoter activity was enhanced in IEC-6 cells by exogenous Pax6 or Pdx1 and diminished in STC-1 cells by inhibition of endogenous Pax6 or Pdx1 by dominant-negative forms. |
| 3060 | 18593849 | EMSA studies indicated that Pax6 and Pdx1 bind to this proximal sequence of the human GIP promoter. |
| 3061 | 18593849 | Our findings indicate that concomitant expression of Pax6 and Pdx1 is important for GIP expression. |
| 3062 | 18593849 | Our results also suggest that the presence of Pdx1 defines whether GLP-1-expressing gastrointestinal L cells also coexpress GIP. |
| 3063 | 18593849 | Pax6 and Pdx1 are required for production of glucose-dependent insulinotropic polypeptide in proglucagon-expressing L cells. |
| 3064 | 18593849 | Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are incretin hormones that play important roles in maintaining glucose homeostasis and are being actively pursued as novel therapeutic agents for diabetes. |
| 3065 | 18593849 | GIP is produced by dispersed enteroendocrine cells and interestingly at times is coexpressed with GLP-1. |
| 3066 | 18593849 | We performed comparative immunostaining of Pax6 and Pdx1 in GIP- and GLP-1-secreting cells. |
| 3067 | 18593849 | We investigated whether Pax6 and Pdx1 activate the human GIP promoter in control IEC-6 cells and GIP-expressing STC-1 cells. |
| 3068 | 18593849 | Pax6 and Pdx1 consistently colocalized in GIP-immunoreactive cells. |
| 3069 | 18593849 | Cells that coexpress GIP and GLP-1 were Pax6 and Pdx1 positive, whereas cells expressing only GLP-1 were Pax6 positive but did not express Pdx1. |
| 3070 | 18593849 | GIP promoter activity was enhanced in IEC-6 cells by exogenous Pax6 or Pdx1 and diminished in STC-1 cells by inhibition of endogenous Pax6 or Pdx1 by dominant-negative forms. |
| 3071 | 18593849 | EMSA studies indicated that Pax6 and Pdx1 bind to this proximal sequence of the human GIP promoter. |
| 3072 | 18593849 | Our findings indicate that concomitant expression of Pax6 and Pdx1 is important for GIP expression. |
| 3073 | 18593849 | Our results also suggest that the presence of Pdx1 defines whether GLP-1-expressing gastrointestinal L cells also coexpress GIP. |
| 3074 | 18593849 | Pax6 and Pdx1 are required for production of glucose-dependent insulinotropic polypeptide in proglucagon-expressing L cells. |
| 3075 | 18593849 | Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are incretin hormones that play important roles in maintaining glucose homeostasis and are being actively pursued as novel therapeutic agents for diabetes. |
| 3076 | 18593849 | GIP is produced by dispersed enteroendocrine cells and interestingly at times is coexpressed with GLP-1. |
| 3077 | 18593849 | We performed comparative immunostaining of Pax6 and Pdx1 in GIP- and GLP-1-secreting cells. |
| 3078 | 18593849 | We investigated whether Pax6 and Pdx1 activate the human GIP promoter in control IEC-6 cells and GIP-expressing STC-1 cells. |
| 3079 | 18593849 | Pax6 and Pdx1 consistently colocalized in GIP-immunoreactive cells. |
| 3080 | 18593849 | Cells that coexpress GIP and GLP-1 were Pax6 and Pdx1 positive, whereas cells expressing only GLP-1 were Pax6 positive but did not express Pdx1. |
| 3081 | 18593849 | GIP promoter activity was enhanced in IEC-6 cells by exogenous Pax6 or Pdx1 and diminished in STC-1 cells by inhibition of endogenous Pax6 or Pdx1 by dominant-negative forms. |
| 3082 | 18593849 | EMSA studies indicated that Pax6 and Pdx1 bind to this proximal sequence of the human GIP promoter. |
| 3083 | 18593849 | Our findings indicate that concomitant expression of Pax6 and Pdx1 is important for GIP expression. |
| 3084 | 18593849 | Our results also suggest that the presence of Pdx1 defines whether GLP-1-expressing gastrointestinal L cells also coexpress GIP. |
| 3085 | 18682608 | To determine the role of cholesterol synthesis in pancreatic beta-cells, a transgenic model of in vivo activation of sterol-regulatory element binding protein 2 (SREBP-2) specifically in beta-cells (TgRIP-SREBP-2) was developed and analyzed. |
| 3086 | 18682608 | Genes involved in beta-cell differentiation, such as PDX1 and BETA2, were suppressed, explaining loss of beta-cell mass, whereas IRS2 expression was not affected. |
| 3087 | 18726523 | Immunocytochemistry results demonstrated that the mhPSC line was positive for the pdx1, glucagon, nestin and CK19, and negative for the insulin, CD34, CD44 and CD45 protein expression. |
| 3088 | 18726523 | RT-PCR revealed further that the mhPSCs expressed transcription factors of the pdx1, glucagon, nestin and CK19. |
| 3089 | 18726523 | Immunocytochemistry results demonstrated that the mhPSC line was positive for the pdx1, glucagon, nestin and CK19, and negative for the insulin, CD34, CD44 and CD45 protein expression. |
| 3090 | 18726523 | RT-PCR revealed further that the mhPSCs expressed transcription factors of the pdx1, glucagon, nestin and CK19. |
| 3091 | 18753309 | Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression. |
| 3092 | 18753309 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP/G6PC2) is a major autoantigen in both mouse and human type 1 diabetes. |
| 3093 | 18753309 | Chromatin immunoprecipitation (ChIP) assays have shown that the IGRP promoter binds the islet-enriched transcription factors Pax-6 and BETA2. |
| 3094 | 18753309 | We show here, again using ChIP assays, that the IGRP promoter also binds the islet-enriched transcription factors MafA and Foxa2. |
| 3095 | 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. |
| 3096 | 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. |
| 3097 | 18753309 | Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression. |
| 3098 | 18753309 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP/G6PC2) is a major autoantigen in both mouse and human type 1 diabetes. |
| 3099 | 18753309 | Chromatin immunoprecipitation (ChIP) assays have shown that the IGRP promoter binds the islet-enriched transcription factors Pax-6 and BETA2. |
| 3100 | 18753309 | We show here, again using ChIP assays, that the IGRP promoter also binds the islet-enriched transcription factors MafA and Foxa2. |
| 3101 | 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. |
| 3102 | 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. |
| 3103 | 18772243 | The homeodomain-interacting protein kinase 2 regulates insulin promoter factor-1/pancreatic duodenal homeobox-1 transcriptional activity. |
| 3104 | 18772243 | The homeodomain transcription factor insulin promoter factor (IPF)-1/pancreatic duodenal homeobox (PDX)-1 plays a crucial role in both pancreas development and maintenance of beta-cell function. |
| 3105 | 18772243 | Targeted disruption of the Ipf1/Pdx1 gene in beta-cells of mice leads to overt diabetes and reduced Ipf1/Pdx1 gene expression results in decreased insulin expression and secretion. |
| 3106 | 18772243 | Moreover, we functionally characterized the role of HIPK2 in regulating IPF1/PDX1 transcriptional activity by performing transient transfection experiments and RNA interference. |
| 3107 | 18772243 | Moreover, we show that HIPK2 positively influences IPF1/PDX1 transcriptional activity and that the kinase activity of HIPK2 is required for this effect. |
| 3108 | 18772243 | We also demonstrate that HIPK2 directly phosphorylates the C-terminal portion of IPF1/PDX1. |
| 3109 | 18772243 | The homeodomain-interacting protein kinase 2 regulates insulin promoter factor-1/pancreatic duodenal homeobox-1 transcriptional activity. |
| 3110 | 18772243 | The homeodomain transcription factor insulin promoter factor (IPF)-1/pancreatic duodenal homeobox (PDX)-1 plays a crucial role in both pancreas development and maintenance of beta-cell function. |
| 3111 | 18772243 | Targeted disruption of the Ipf1/Pdx1 gene in beta-cells of mice leads to overt diabetes and reduced Ipf1/Pdx1 gene expression results in decreased insulin expression and secretion. |
| 3112 | 18772243 | Moreover, we functionally characterized the role of HIPK2 in regulating IPF1/PDX1 transcriptional activity by performing transient transfection experiments and RNA interference. |
| 3113 | 18772243 | Moreover, we show that HIPK2 positively influences IPF1/PDX1 transcriptional activity and that the kinase activity of HIPK2 is required for this effect. |
| 3114 | 18772243 | We also demonstrate that HIPK2 directly phosphorylates the C-terminal portion of IPF1/PDX1. |
| 3115 | 18772243 | The homeodomain-interacting protein kinase 2 regulates insulin promoter factor-1/pancreatic duodenal homeobox-1 transcriptional activity. |
| 3116 | 18772243 | The homeodomain transcription factor insulin promoter factor (IPF)-1/pancreatic duodenal homeobox (PDX)-1 plays a crucial role in both pancreas development and maintenance of beta-cell function. |
| 3117 | 18772243 | Targeted disruption of the Ipf1/Pdx1 gene in beta-cells of mice leads to overt diabetes and reduced Ipf1/Pdx1 gene expression results in decreased insulin expression and secretion. |
| 3118 | 18772243 | Moreover, we functionally characterized the role of HIPK2 in regulating IPF1/PDX1 transcriptional activity by performing transient transfection experiments and RNA interference. |
| 3119 | 18772243 | Moreover, we show that HIPK2 positively influences IPF1/PDX1 transcriptional activity and that the kinase activity of HIPK2 is required for this effect. |
| 3120 | 18772243 | We also demonstrate that HIPK2 directly phosphorylates the C-terminal portion of IPF1/PDX1. |
| 3121 | 18772243 | The homeodomain-interacting protein kinase 2 regulates insulin promoter factor-1/pancreatic duodenal homeobox-1 transcriptional activity. |
| 3122 | 18772243 | The homeodomain transcription factor insulin promoter factor (IPF)-1/pancreatic duodenal homeobox (PDX)-1 plays a crucial role in both pancreas development and maintenance of beta-cell function. |
| 3123 | 18772243 | Targeted disruption of the Ipf1/Pdx1 gene in beta-cells of mice leads to overt diabetes and reduced Ipf1/Pdx1 gene expression results in decreased insulin expression and secretion. |
| 3124 | 18772243 | Moreover, we functionally characterized the role of HIPK2 in regulating IPF1/PDX1 transcriptional activity by performing transient transfection experiments and RNA interference. |
| 3125 | 18772243 | Moreover, we show that HIPK2 positively influences IPF1/PDX1 transcriptional activity and that the kinase activity of HIPK2 is required for this effect. |
| 3126 | 18772243 | We also demonstrate that HIPK2 directly phosphorylates the C-terminal portion of IPF1/PDX1. |
| 3127 | 18772243 | The homeodomain-interacting protein kinase 2 regulates insulin promoter factor-1/pancreatic duodenal homeobox-1 transcriptional activity. |
| 3128 | 18772243 | The homeodomain transcription factor insulin promoter factor (IPF)-1/pancreatic duodenal homeobox (PDX)-1 plays a crucial role in both pancreas development and maintenance of beta-cell function. |
| 3129 | 18772243 | Targeted disruption of the Ipf1/Pdx1 gene in beta-cells of mice leads to overt diabetes and reduced Ipf1/Pdx1 gene expression results in decreased insulin expression and secretion. |
| 3130 | 18772243 | Moreover, we functionally characterized the role of HIPK2 in regulating IPF1/PDX1 transcriptional activity by performing transient transfection experiments and RNA interference. |
| 3131 | 18772243 | Moreover, we show that HIPK2 positively influences IPF1/PDX1 transcriptional activity and that the kinase activity of HIPK2 is required for this effect. |
| 3132 | 18772243 | We also demonstrate that HIPK2 directly phosphorylates the C-terminal portion of IPF1/PDX1. |
| 3133 | 18772243 | The homeodomain-interacting protein kinase 2 regulates insulin promoter factor-1/pancreatic duodenal homeobox-1 transcriptional activity. |
| 3134 | 18772243 | The homeodomain transcription factor insulin promoter factor (IPF)-1/pancreatic duodenal homeobox (PDX)-1 plays a crucial role in both pancreas development and maintenance of beta-cell function. |
| 3135 | 18772243 | Targeted disruption of the Ipf1/Pdx1 gene in beta-cells of mice leads to overt diabetes and reduced Ipf1/Pdx1 gene expression results in decreased insulin expression and secretion. |
| 3136 | 18772243 | Moreover, we functionally characterized the role of HIPK2 in regulating IPF1/PDX1 transcriptional activity by performing transient transfection experiments and RNA interference. |
| 3137 | 18772243 | Moreover, we show that HIPK2 positively influences IPF1/PDX1 transcriptional activity and that the kinase activity of HIPK2 is required for this effect. |
| 3138 | 18772243 | We also demonstrate that HIPK2 directly phosphorylates the C-terminal portion of IPF1/PDX1. |
| 3139 | 18813850 | When cultured in the presence of HGF and FGF-4 on Matrigel, rBM25/S3 cells expressed genes specific to pancreatic beta-cells as well as those specific to hepatocytes. |
| 3140 | 18813850 | These hepato-pancreatic intermediate progenitor cells, but not the original undifferentiated rBM25/S3 cells, were induced by the overexpression of PDX-1 to produce significant amounts of insulin in a manner responding to glucose concentration in medium. |
| 3141 | 18836005 | Commensal strains were engineered to secrete the insulinotropic proteins GLP-1 and PDX-1. |
| 3142 | 18850229 | Extracts of Rehmanniae radix, Ginseng radix and Scutellariae radix improve glucose-stimulated insulin secretion and beta-cell proliferation through IRS2 induction. |
| 3143 | 18850229 | In this study, we investigated whether herbs used for treating diabetes in Chinese medicine-Galla rhois, Rehmanniae radix, Machilus bark, Ginseng radix, Polygonatum radix, and Scutellariae radix-improved IRS2 induction in rat islets, glucose-stimulated insulin secretion and beta-cell survival. |
| 3144 | 18850229 | These herbs induced the expression of IRS2, pancreas duodenum homeobox-1 (PDX-1), and glucokinase. |
| 3145 | 18850229 | The increased level of glucokinase could explain the enhancement of glucose-stimulated insulin secretion with these extracts. |
| 3146 | 18940247 | Concurrent with reduction in mitochondrial membrane potential (DeltaPsim) and cellular ATP content, impaired mitochondrial function reduced GCK expression and resulted in decreased insulin secretion and beta-cell apoptosis. |
| 3147 | 18940247 | Specifically, lowered GCK expression led to decreased interactions between GCK and mitochondria, which increased Bax binding to mitochondria and cytochrome C release into cytoplasm. |
| 3148 | 18940247 | Moreover, examination of the GCK promoter in antimycin-treated cells demonstrated that the promoter region within -287 bases from transcription site is involved in the transcriptional repression of GCK by mitochondrial stress, whose region contains a putative binding site for pancreatic duodenal homeobox-1 (PDX-1). |
| 3149 | 18940247 | Mitochondrial stress reduced PDX-1 expression, and increased ATF3 expression dependent on reactive oxygen species (ROS). |
| 3150 | 18940247 | Collectively, these data demonstrate that mitochondrial dysfunction by metabolic stress reduces GCK expression through PDX-1 downregulation via production of ROS, which then decreases the association of GCK with mitochondria, resulting in pancreatic beta-cell apoptosis and reduction of insulin secretion. |
| 3151 | 18940247 | Concurrent with reduction in mitochondrial membrane potential (DeltaPsim) and cellular ATP content, impaired mitochondrial function reduced GCK expression and resulted in decreased insulin secretion and beta-cell apoptosis. |
| 3152 | 18940247 | Specifically, lowered GCK expression led to decreased interactions between GCK and mitochondria, which increased Bax binding to mitochondria and cytochrome C release into cytoplasm. |
| 3153 | 18940247 | Moreover, examination of the GCK promoter in antimycin-treated cells demonstrated that the promoter region within -287 bases from transcription site is involved in the transcriptional repression of GCK by mitochondrial stress, whose region contains a putative binding site for pancreatic duodenal homeobox-1 (PDX-1). |
| 3154 | 18940247 | Mitochondrial stress reduced PDX-1 expression, and increased ATF3 expression dependent on reactive oxygen species (ROS). |
| 3155 | 18940247 | Collectively, these data demonstrate that mitochondrial dysfunction by metabolic stress reduces GCK expression through PDX-1 downregulation via production of ROS, which then decreases the association of GCK with mitochondria, resulting in pancreatic beta-cell apoptosis and reduction of insulin secretion. |
| 3156 | 18940247 | Concurrent with reduction in mitochondrial membrane potential (DeltaPsim) and cellular ATP content, impaired mitochondrial function reduced GCK expression and resulted in decreased insulin secretion and beta-cell apoptosis. |
| 3157 | 18940247 | Specifically, lowered GCK expression led to decreased interactions between GCK and mitochondria, which increased Bax binding to mitochondria and cytochrome C release into cytoplasm. |
| 3158 | 18940247 | Moreover, examination of the GCK promoter in antimycin-treated cells demonstrated that the promoter region within -287 bases from transcription site is involved in the transcriptional repression of GCK by mitochondrial stress, whose region contains a putative binding site for pancreatic duodenal homeobox-1 (PDX-1). |
| 3159 | 18940247 | Mitochondrial stress reduced PDX-1 expression, and increased ATF3 expression dependent on reactive oxygen species (ROS). |
| 3160 | 18940247 | Collectively, these data demonstrate that mitochondrial dysfunction by metabolic stress reduces GCK expression through PDX-1 downregulation via production of ROS, which then decreases the association of GCK with mitochondria, resulting in pancreatic beta-cell apoptosis and reduction of insulin secretion. |
| 3161 | 18951876 | Insulin gene is a target in activin receptor-like kinase 7 signaling pathway in pancreatic beta-cells. |
| 3162 | 18951876 | In this study, human insulin promoter was activated by Smad2, Smad3 and the pancreatic and duodenal homeobox factor-1 (PDX-1) in the ALK7 pathway. |
| 3163 | 18951876 | Phosphorylated Smad2/Smad3 and PDX-1 were bound to insulin gene with Nodal and Activin AB, and the phosphorylated Smad2/Smad3 interacted with PDX-1. |
| 3164 | 18951876 | These results indicate that one of the direct target genes of Nodal and Activin AB signals is the insulin gene in pancreatic beta-cells and that PDX-1 is directly involved in the ALK7-Smad pathway. |
| 3165 | 18951876 | Insulin gene is a target in activin receptor-like kinase 7 signaling pathway in pancreatic beta-cells. |
| 3166 | 18951876 | In this study, human insulin promoter was activated by Smad2, Smad3 and the pancreatic and duodenal homeobox factor-1 (PDX-1) in the ALK7 pathway. |
| 3167 | 18951876 | Phosphorylated Smad2/Smad3 and PDX-1 were bound to insulin gene with Nodal and Activin AB, and the phosphorylated Smad2/Smad3 interacted with PDX-1. |
| 3168 | 18951876 | These results indicate that one of the direct target genes of Nodal and Activin AB signals is the insulin gene in pancreatic beta-cells and that PDX-1 is directly involved in the ALK7-Smad pathway. |
| 3169 | 18951876 | Insulin gene is a target in activin receptor-like kinase 7 signaling pathway in pancreatic beta-cells. |
| 3170 | 18951876 | In this study, human insulin promoter was activated by Smad2, Smad3 and the pancreatic and duodenal homeobox factor-1 (PDX-1) in the ALK7 pathway. |
| 3171 | 18951876 | Phosphorylated Smad2/Smad3 and PDX-1 were bound to insulin gene with Nodal and Activin AB, and the phosphorylated Smad2/Smad3 interacted with PDX-1. |
| 3172 | 18951876 | These results indicate that one of the direct target genes of Nodal and Activin AB signals is the insulin gene in pancreatic beta-cells and that PDX-1 is directly involved in the ALK7-Smad pathway. |
| 3173 | 19023675 | Common ligands for the alpha3beta1 integrin, including fibronectin, laminin, collagen I and collagen IV were tested to identify the most suitable matrix for INS-1 cell proliferation and function. |
| 3174 | 19023675 | Cells exposed to collagen I and IV demonstrated significant increases in adhesion, spreading, cell viability, proliferation, and FAK phosphorylation when compared to cells cultured on fibronectin, laminin and controls. |
| 3175 | 19023675 | Integrin-dependent attachment also had a beneficial effect on beta cell function, increasing Pdx-1 and insulin gene and protein expression on collagens I and IV, in parallel with increased basal insulin release and enhanced insulin secretion upon high glucose challenge. |
| 3176 | 19023675 | Furthermore, functional blockade of alpha3beta1 integrin decreased cell adhesion, spreading and viability on both collagens and reduced Pdx-1 and insulin expression, indicating that its interactions with collagen matrices are important for beta cell survival and function. |
| 3177 | 19023675 | Common ligands for the alpha3beta1 integrin, including fibronectin, laminin, collagen I and collagen IV were tested to identify the most suitable matrix for INS-1 cell proliferation and function. |
| 3178 | 19023675 | Cells exposed to collagen I and IV demonstrated significant increases in adhesion, spreading, cell viability, proliferation, and FAK phosphorylation when compared to cells cultured on fibronectin, laminin and controls. |
| 3179 | 19023675 | Integrin-dependent attachment also had a beneficial effect on beta cell function, increasing Pdx-1 and insulin gene and protein expression on collagens I and IV, in parallel with increased basal insulin release and enhanced insulin secretion upon high glucose challenge. |
| 3180 | 19023675 | Furthermore, functional blockade of alpha3beta1 integrin decreased cell adhesion, spreading and viability on both collagens and reduced Pdx-1 and insulin expression, indicating that its interactions with collagen matrices are important for beta cell survival and function. |
| 3181 | 19062254 | Autologous bone marrow-derived rat mesenchymal stem cells promote PDX-1 and insulin expression in the islets, alter T cell cytokine pattern and preserve regulatory T cells in the periphery and induce sustained normoglycemia. |
| 3182 | 19062254 | MSC were CD45(-)/CD44(+)/CD54(+)/CD90(+)/CD106(+). |
| 3183 | 19062254 | MSC spontaneously secreted IL-6, HGF, TGF-beta1 and expressed high levels of SDF-1 and low levels of VEGF, IL-1beta and PGE(2), but no EGF, insulin or glucagon. |
| 3184 | 19062254 | Interestingly, immunohistochemistry demonstrated that, the islets from MSC-treated rats expressed high levels of PDX-1 and that these cells were also positive for insulin staining. |
| 3185 | 19062254 | In addition, peripheral T cells from MSC-treated rats exhibited a shift toward IL-10/IL-13 production and higher frequencies of CD4(+)/CD8(+) Foxp3(+) T cells compared to the PBS-treated rats. |
| 3186 | 19062254 | Autologous bone marrow-derived rat mesenchymal stem cells promote PDX-1 and insulin expression in the islets, alter T cell cytokine pattern and preserve regulatory T cells in the periphery and induce sustained normoglycemia. |
| 3187 | 19062254 | MSC were CD45(-)/CD44(+)/CD54(+)/CD90(+)/CD106(+). |
| 3188 | 19062254 | MSC spontaneously secreted IL-6, HGF, TGF-beta1 and expressed high levels of SDF-1 and low levels of VEGF, IL-1beta and PGE(2), but no EGF, insulin or glucagon. |
| 3189 | 19062254 | Interestingly, immunohistochemistry demonstrated that, the islets from MSC-treated rats expressed high levels of PDX-1 and that these cells were also positive for insulin staining. |
| 3190 | 19062254 | In addition, peripheral T cells from MSC-treated rats exhibited a shift toward IL-10/IL-13 production and higher frequencies of CD4(+)/CD8(+) Foxp3(+) T cells compared to the PBS-treated rats. |
| 3191 | 19095744 | Maturation of adult beta-cells revealed using a Pdx1/insulin dual-reporter lentivirus. |
| 3192 | 19095744 | This study examined the dynamics and heterogeneity of insulin and pancreatic duodenal homeobox (Pdx)-1 gene expression in adult beta-cells. |
| 3193 | 19095744 | Insulin and Pdx1 expression were monitored in human and mouse islet cells and MIN6 cells using a Pdx1-monomeric red fluorescent protein/insulin-enhanced green fluorescent protein dual-reporter lentivirus. |
| 3194 | 19095744 | Cells expressing Pdx1 but little or no insulin (Pdx1(+)/Ins(low)) comprised 15-25% of the total population. |
| 3195 | 19095744 | Genes involved in the mature beta-cell phenotype (Glut2, MafA) were expressed at higher levels in Pdx1(+)/Ins(+) cells relative to Pdx1(+)/Ins(low) cells. |
| 3196 | 19095744 | Conversely, genes implicated in early beta-cell development (MafB, Nkx2.2) were enriched in Pdx1(+)/Ins(low) cells. |
| 3197 | 19095744 | Sorted Pdx1(+)/Ins(low) MIN6 cells had a higher replication rate and secreted less insulin relative to double-positive cells. |
| 3198 | 19095744 | These results demonstrate that adult beta-cells pass through distinct maturation states, which is consistent with previously observed heterogeneity in insulin and Pdx1 expression in adult beta-cells. |
| 3199 | 19095744 | The maturation of adult beta-cells recapitulates development in that Pdx1 expression precedes the robust expression of insulin and other mature beta-cell genes. |
| 3200 | 19095744 | Maturation of adult beta-cells revealed using a Pdx1/insulin dual-reporter lentivirus. |
| 3201 | 19095744 | This study examined the dynamics and heterogeneity of insulin and pancreatic duodenal homeobox (Pdx)-1 gene expression in adult beta-cells. |
| 3202 | 19095744 | Insulin and Pdx1 expression were monitored in human and mouse islet cells and MIN6 cells using a Pdx1-monomeric red fluorescent protein/insulin-enhanced green fluorescent protein dual-reporter lentivirus. |
| 3203 | 19095744 | Cells expressing Pdx1 but little or no insulin (Pdx1(+)/Ins(low)) comprised 15-25% of the total population. |
| 3204 | 19095744 | Genes involved in the mature beta-cell phenotype (Glut2, MafA) were expressed at higher levels in Pdx1(+)/Ins(+) cells relative to Pdx1(+)/Ins(low) cells. |
| 3205 | 19095744 | Conversely, genes implicated in early beta-cell development (MafB, Nkx2.2) were enriched in Pdx1(+)/Ins(low) cells. |
| 3206 | 19095744 | Sorted Pdx1(+)/Ins(low) MIN6 cells had a higher replication rate and secreted less insulin relative to double-positive cells. |
| 3207 | 19095744 | These results demonstrate that adult beta-cells pass through distinct maturation states, which is consistent with previously observed heterogeneity in insulin and Pdx1 expression in adult beta-cells. |
| 3208 | 19095744 | The maturation of adult beta-cells recapitulates development in that Pdx1 expression precedes the robust expression of insulin and other mature beta-cell genes. |
| 3209 | 19095744 | Maturation of adult beta-cells revealed using a Pdx1/insulin dual-reporter lentivirus. |
| 3210 | 19095744 | This study examined the dynamics and heterogeneity of insulin and pancreatic duodenal homeobox (Pdx)-1 gene expression in adult beta-cells. |
| 3211 | 19095744 | Insulin and Pdx1 expression were monitored in human and mouse islet cells and MIN6 cells using a Pdx1-monomeric red fluorescent protein/insulin-enhanced green fluorescent protein dual-reporter lentivirus. |
| 3212 | 19095744 | Cells expressing Pdx1 but little or no insulin (Pdx1(+)/Ins(low)) comprised 15-25% of the total population. |
| 3213 | 19095744 | Genes involved in the mature beta-cell phenotype (Glut2, MafA) were expressed at higher levels in Pdx1(+)/Ins(+) cells relative to Pdx1(+)/Ins(low) cells. |
| 3214 | 19095744 | Conversely, genes implicated in early beta-cell development (MafB, Nkx2.2) were enriched in Pdx1(+)/Ins(low) cells. |
| 3215 | 19095744 | Sorted Pdx1(+)/Ins(low) MIN6 cells had a higher replication rate and secreted less insulin relative to double-positive cells. |
| 3216 | 19095744 | These results demonstrate that adult beta-cells pass through distinct maturation states, which is consistent with previously observed heterogeneity in insulin and Pdx1 expression in adult beta-cells. |
| 3217 | 19095744 | The maturation of adult beta-cells recapitulates development in that Pdx1 expression precedes the robust expression of insulin and other mature beta-cell genes. |
| 3218 | 19095744 | Maturation of adult beta-cells revealed using a Pdx1/insulin dual-reporter lentivirus. |
| 3219 | 19095744 | This study examined the dynamics and heterogeneity of insulin and pancreatic duodenal homeobox (Pdx)-1 gene expression in adult beta-cells. |
| 3220 | 19095744 | Insulin and Pdx1 expression were monitored in human and mouse islet cells and MIN6 cells using a Pdx1-monomeric red fluorescent protein/insulin-enhanced green fluorescent protein dual-reporter lentivirus. |
| 3221 | 19095744 | Cells expressing Pdx1 but little or no insulin (Pdx1(+)/Ins(low)) comprised 15-25% of the total population. |
| 3222 | 19095744 | Genes involved in the mature beta-cell phenotype (Glut2, MafA) were expressed at higher levels in Pdx1(+)/Ins(+) cells relative to Pdx1(+)/Ins(low) cells. |
| 3223 | 19095744 | Conversely, genes implicated in early beta-cell development (MafB, Nkx2.2) were enriched in Pdx1(+)/Ins(low) cells. |
| 3224 | 19095744 | Sorted Pdx1(+)/Ins(low) MIN6 cells had a higher replication rate and secreted less insulin relative to double-positive cells. |
| 3225 | 19095744 | These results demonstrate that adult beta-cells pass through distinct maturation states, which is consistent with previously observed heterogeneity in insulin and Pdx1 expression in adult beta-cells. |
| 3226 | 19095744 | The maturation of adult beta-cells recapitulates development in that Pdx1 expression precedes the robust expression of insulin and other mature beta-cell genes. |
| 3227 | 19095744 | Maturation of adult beta-cells revealed using a Pdx1/insulin dual-reporter lentivirus. |
| 3228 | 19095744 | This study examined the dynamics and heterogeneity of insulin and pancreatic duodenal homeobox (Pdx)-1 gene expression in adult beta-cells. |
| 3229 | 19095744 | Insulin and Pdx1 expression were monitored in human and mouse islet cells and MIN6 cells using a Pdx1-monomeric red fluorescent protein/insulin-enhanced green fluorescent protein dual-reporter lentivirus. |
| 3230 | 19095744 | Cells expressing Pdx1 but little or no insulin (Pdx1(+)/Ins(low)) comprised 15-25% of the total population. |
| 3231 | 19095744 | Genes involved in the mature beta-cell phenotype (Glut2, MafA) were expressed at higher levels in Pdx1(+)/Ins(+) cells relative to Pdx1(+)/Ins(low) cells. |
| 3232 | 19095744 | Conversely, genes implicated in early beta-cell development (MafB, Nkx2.2) were enriched in Pdx1(+)/Ins(low) cells. |
| 3233 | 19095744 | Sorted Pdx1(+)/Ins(low) MIN6 cells had a higher replication rate and secreted less insulin relative to double-positive cells. |
| 3234 | 19095744 | These results demonstrate that adult beta-cells pass through distinct maturation states, which is consistent with previously observed heterogeneity in insulin and Pdx1 expression in adult beta-cells. |
| 3235 | 19095744 | The maturation of adult beta-cells recapitulates development in that Pdx1 expression precedes the robust expression of insulin and other mature beta-cell genes. |
| 3236 | 19095744 | Maturation of adult beta-cells revealed using a Pdx1/insulin dual-reporter lentivirus. |
| 3237 | 19095744 | This study examined the dynamics and heterogeneity of insulin and pancreatic duodenal homeobox (Pdx)-1 gene expression in adult beta-cells. |
| 3238 | 19095744 | Insulin and Pdx1 expression were monitored in human and mouse islet cells and MIN6 cells using a Pdx1-monomeric red fluorescent protein/insulin-enhanced green fluorescent protein dual-reporter lentivirus. |
| 3239 | 19095744 | Cells expressing Pdx1 but little or no insulin (Pdx1(+)/Ins(low)) comprised 15-25% of the total population. |
| 3240 | 19095744 | Genes involved in the mature beta-cell phenotype (Glut2, MafA) were expressed at higher levels in Pdx1(+)/Ins(+) cells relative to Pdx1(+)/Ins(low) cells. |
| 3241 | 19095744 | Conversely, genes implicated in early beta-cell development (MafB, Nkx2.2) were enriched in Pdx1(+)/Ins(low) cells. |
| 3242 | 19095744 | Sorted Pdx1(+)/Ins(low) MIN6 cells had a higher replication rate and secreted less insulin relative to double-positive cells. |
| 3243 | 19095744 | These results demonstrate that adult beta-cells pass through distinct maturation states, which is consistent with previously observed heterogeneity in insulin and Pdx1 expression in adult beta-cells. |
| 3244 | 19095744 | The maturation of adult beta-cells recapitulates development in that Pdx1 expression precedes the robust expression of insulin and other mature beta-cell genes. |
| 3245 | 19095744 | Maturation of adult beta-cells revealed using a Pdx1/insulin dual-reporter lentivirus. |
| 3246 | 19095744 | This study examined the dynamics and heterogeneity of insulin and pancreatic duodenal homeobox (Pdx)-1 gene expression in adult beta-cells. |
| 3247 | 19095744 | Insulin and Pdx1 expression were monitored in human and mouse islet cells and MIN6 cells using a Pdx1-monomeric red fluorescent protein/insulin-enhanced green fluorescent protein dual-reporter lentivirus. |
| 3248 | 19095744 | Cells expressing Pdx1 but little or no insulin (Pdx1(+)/Ins(low)) comprised 15-25% of the total population. |
| 3249 | 19095744 | Genes involved in the mature beta-cell phenotype (Glut2, MafA) were expressed at higher levels in Pdx1(+)/Ins(+) cells relative to Pdx1(+)/Ins(low) cells. |
| 3250 | 19095744 | Conversely, genes implicated in early beta-cell development (MafB, Nkx2.2) were enriched in Pdx1(+)/Ins(low) cells. |
| 3251 | 19095744 | Sorted Pdx1(+)/Ins(low) MIN6 cells had a higher replication rate and secreted less insulin relative to double-positive cells. |
| 3252 | 19095744 | These results demonstrate that adult beta-cells pass through distinct maturation states, which is consistent with previously observed heterogeneity in insulin and Pdx1 expression in adult beta-cells. |
| 3253 | 19095744 | The maturation of adult beta-cells recapitulates development in that Pdx1 expression precedes the robust expression of insulin and other mature beta-cell genes. |
| 3254 | 19095744 | Maturation of adult beta-cells revealed using a Pdx1/insulin dual-reporter lentivirus. |
| 3255 | 19095744 | This study examined the dynamics and heterogeneity of insulin and pancreatic duodenal homeobox (Pdx)-1 gene expression in adult beta-cells. |
| 3256 | 19095744 | Insulin and Pdx1 expression were monitored in human and mouse islet cells and MIN6 cells using a Pdx1-monomeric red fluorescent protein/insulin-enhanced green fluorescent protein dual-reporter lentivirus. |
| 3257 | 19095744 | Cells expressing Pdx1 but little or no insulin (Pdx1(+)/Ins(low)) comprised 15-25% of the total population. |
| 3258 | 19095744 | Genes involved in the mature beta-cell phenotype (Glut2, MafA) were expressed at higher levels in Pdx1(+)/Ins(+) cells relative to Pdx1(+)/Ins(low) cells. |
| 3259 | 19095744 | Conversely, genes implicated in early beta-cell development (MafB, Nkx2.2) were enriched in Pdx1(+)/Ins(low) cells. |
| 3260 | 19095744 | Sorted Pdx1(+)/Ins(low) MIN6 cells had a higher replication rate and secreted less insulin relative to double-positive cells. |
| 3261 | 19095744 | These results demonstrate that adult beta-cells pass through distinct maturation states, which is consistent with previously observed heterogeneity in insulin and Pdx1 expression in adult beta-cells. |
| 3262 | 19095744 | The maturation of adult beta-cells recapitulates development in that Pdx1 expression precedes the robust expression of insulin and other mature beta-cell genes. |
| 3263 | 19095744 | Maturation of adult beta-cells revealed using a Pdx1/insulin dual-reporter lentivirus. |
| 3264 | 19095744 | This study examined the dynamics and heterogeneity of insulin and pancreatic duodenal homeobox (Pdx)-1 gene expression in adult beta-cells. |
| 3265 | 19095744 | Insulin and Pdx1 expression were monitored in human and mouse islet cells and MIN6 cells using a Pdx1-monomeric red fluorescent protein/insulin-enhanced green fluorescent protein dual-reporter lentivirus. |
| 3266 | 19095744 | Cells expressing Pdx1 but little or no insulin (Pdx1(+)/Ins(low)) comprised 15-25% of the total population. |
| 3267 | 19095744 | Genes involved in the mature beta-cell phenotype (Glut2, MafA) were expressed at higher levels in Pdx1(+)/Ins(+) cells relative to Pdx1(+)/Ins(low) cells. |
| 3268 | 19095744 | Conversely, genes implicated in early beta-cell development (MafB, Nkx2.2) were enriched in Pdx1(+)/Ins(low) cells. |
| 3269 | 19095744 | Sorted Pdx1(+)/Ins(low) MIN6 cells had a higher replication rate and secreted less insulin relative to double-positive cells. |
| 3270 | 19095744 | These results demonstrate that adult beta-cells pass through distinct maturation states, which is consistent with previously observed heterogeneity in insulin and Pdx1 expression in adult beta-cells. |
| 3271 | 19095744 | The maturation of adult beta-cells recapitulates development in that Pdx1 expression precedes the robust expression of insulin and other mature beta-cell genes. |
| 3272 | 19135250 | However, in addition to insulin/c-peptide, most cells also coexpressed PDX-1 (pancreas duodenum homeobox-1), glucagon, somatostatin or pancreatic polypeptide. |
| 3273 | 19168505 | At day 14, IHBECs were transfected with adenoviral (Ad)- pancreas duodenum homeobox 1 (Pdx-1), NeuroD or Pdx-1/VP16. |
| 3274 | 19168505 | In DM control IHBECs started to express some endocrine progenitor genes (Neurog3, NeuroD, Nkx6.1, and Pdx-1) but lacked insulin gene (Ins) mRNA. |
| 3275 | 19168505 | Transduced expression of PDX-1, NEUROD or PDX-1/VP16 led to expression of not only INS but also GLUT2 and prohormone convertase 1 and 2. |
| 3276 | 19168505 | Transduced cells released insulin (Ad-PDX-1 0.08+/-0.05, Ad-NEUROD 0.33+/-0.09, Ad-PDX-1/VP16 0.37+/-0.14 ng/1x10(5) cells after 48 h in culture). |
| 3277 | 19168505 | At day 14, IHBECs were transfected with adenoviral (Ad)- pancreas duodenum homeobox 1 (Pdx-1), NeuroD or Pdx-1/VP16. |
| 3278 | 19168505 | In DM control IHBECs started to express some endocrine progenitor genes (Neurog3, NeuroD, Nkx6.1, and Pdx-1) but lacked insulin gene (Ins) mRNA. |
| 3279 | 19168505 | Transduced expression of PDX-1, NEUROD or PDX-1/VP16 led to expression of not only INS but also GLUT2 and prohormone convertase 1 and 2. |
| 3280 | 19168505 | Transduced cells released insulin (Ad-PDX-1 0.08+/-0.05, Ad-NEUROD 0.33+/-0.09, Ad-PDX-1/VP16 0.37+/-0.14 ng/1x10(5) cells after 48 h in culture). |
| 3281 | 19168505 | At day 14, IHBECs were transfected with adenoviral (Ad)- pancreas duodenum homeobox 1 (Pdx-1), NeuroD or Pdx-1/VP16. |
| 3282 | 19168505 | In DM control IHBECs started to express some endocrine progenitor genes (Neurog3, NeuroD, Nkx6.1, and Pdx-1) but lacked insulin gene (Ins) mRNA. |
| 3283 | 19168505 | Transduced expression of PDX-1, NEUROD or PDX-1/VP16 led to expression of not only INS but also GLUT2 and prohormone convertase 1 and 2. |
| 3284 | 19168505 | Transduced cells released insulin (Ad-PDX-1 0.08+/-0.05, Ad-NEUROD 0.33+/-0.09, Ad-PDX-1/VP16 0.37+/-0.14 ng/1x10(5) cells after 48 h in culture). |
| 3285 | 19168505 | At day 14, IHBECs were transfected with adenoviral (Ad)- pancreas duodenum homeobox 1 (Pdx-1), NeuroD or Pdx-1/VP16. |
| 3286 | 19168505 | In DM control IHBECs started to express some endocrine progenitor genes (Neurog3, NeuroD, Nkx6.1, and Pdx-1) but lacked insulin gene (Ins) mRNA. |
| 3287 | 19168505 | Transduced expression of PDX-1, NEUROD or PDX-1/VP16 led to expression of not only INS but also GLUT2 and prohormone convertase 1 and 2. |
| 3288 | 19168505 | Transduced cells released insulin (Ad-PDX-1 0.08+/-0.05, Ad-NEUROD 0.33+/-0.09, Ad-PDX-1/VP16 0.37+/-0.14 ng/1x10(5) cells after 48 h in culture). |
| 3289 | 19213833 | The expression of GPR39 is regulated by hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha, and in the present study, we addressed the importance of GPR39 for glucose homeostasis and pancreatic islets function. |
| 3290 | 19213833 | Gpr39(-/-) mice were studied in vivo, especially in respect of glucose tolerance and insulin sensitivity, and in vitro in respect of islet architecture, gene expression, and insulin secretion. |
| 3291 | 19213833 | Gpr39 was down-regulated on differentiation of the pluripotent pancreatic cell line AR42J cells toward the exocrine phenotype but was along with Pdx-1 strongly up-regulated on differentiation toward the endocrine phenotype. |
| 3292 | 19213833 | Gpr39(-/-) mice displayed normal insulin sensitivity but moderately impaired glucose tolerance both during oral and iv glucose tolerance tests, and Gpr39(-/-) mice had decreased plasma insulin response to oral glucose. |
| 3293 | 19213833 | Islet architecture was normal in the Gpr39 null mice, but expression of Pdx-1 and Hnf-1alpha was reduced. |
| 3294 | 19213833 | Isolated, perifused islets from Gpr39 null mice secreted less insulin in response to glucose stimulation than islets from wild-type littermates. |
| 3295 | 19213833 | The expression of GPR39 is regulated by hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha, and in the present study, we addressed the importance of GPR39 for glucose homeostasis and pancreatic islets function. |
| 3296 | 19213833 | Gpr39(-/-) mice were studied in vivo, especially in respect of glucose tolerance and insulin sensitivity, and in vitro in respect of islet architecture, gene expression, and insulin secretion. |
| 3297 | 19213833 | Gpr39 was down-regulated on differentiation of the pluripotent pancreatic cell line AR42J cells toward the exocrine phenotype but was along with Pdx-1 strongly up-regulated on differentiation toward the endocrine phenotype. |
| 3298 | 19213833 | Gpr39(-/-) mice displayed normal insulin sensitivity but moderately impaired glucose tolerance both during oral and iv glucose tolerance tests, and Gpr39(-/-) mice had decreased plasma insulin response to oral glucose. |
| 3299 | 19213833 | Islet architecture was normal in the Gpr39 null mice, but expression of Pdx-1 and Hnf-1alpha was reduced. |
| 3300 | 19213833 | Isolated, perifused islets from Gpr39 null mice secreted less insulin in response to glucose stimulation than islets from wild-type littermates. |
| 3301 | 19213841 | Disruption of G protein-coupled receptor 39 impairs insulin secretion in vivo. |
| 3302 | 19213841 | We have recently shown that young GPR39(-/-) mice have normal body weight, food intake, and fasting glucose and insulin levels. |
| 3303 | 19213841 | Fifty-two-week-old GPR39(-/-) mice showed a trend toward decreased insulin levels after oral glucose challenge. |
| 3304 | 19213841 | When fed either a low-fat/high-sucrose or high-fat/high-sucrose diet, GPR39(-/-) mice had increased fed glucose levels and showed decreased serum insulin levels during an oral glucose tolerance test in the face of unchanged insulin tolerance. |
| 3305 | 19213841 | Pancreas morphology and glucose-stimulated insulin secretion in isolated islets from wild-type and GPR39(-/-) mice were comparable, suggesting that GPR39 is not required for pancreas development or ex vivo insulin secretion. |
| 3306 | 19213841 | Small interfering RNA-mediated knockdown of GPR39 in clonal NIT-1 beta-cells revealed that GPR39 regulates the expression of insulin receptor substrate-2 and pancreatic and duodenal homeobox-1 in a cell-autonomous manner; insulin receptor substrate-2 mRNA was also significantly decreased in the pancreas of GPR39(-/-) mice. |
| 3307 | 19213841 | Taken together, our data indicate that GPR39 is required for the increased insulin secretion in vivo under conditions of increased demand, i.e. on development of age-dependent and diet-induced insulin resistance. |
| 3308 | 19237535 | This improved islet function was at least partially attributed to significant upregulation of the islet genes Irs1, SERCA, Ins1/2, and Glut2 in treated animals. |
| 3309 | 19237535 | The restoration of the Ins1/2 and Glut2 genes corresponded to a two- to threefold increase in the euchromatin marker histone H3 dimethyl-Lys4 at their respective promoters and was coincident with increased nuclear occupancy of the islet methyltransferase Set7/9. |
| 3310 | 19237535 | Consistent with this possibility, incubation of thapsigargin-treated INS-1 beta cells with the PPAR-gamma agonist resulted in the reduction of endoplasmic reticulum stress and restoration of Pdx1 protein levels and Set7/9 nuclear occupancy. |
| 3311 | 19237535 | We conclude that PPAR-gamma agonists exert a direct effect in diabetic islets to reduce endoplasmic reticulum stress and enhance Pdx1 levels, leading to favorable alterations of the islet gene chromatin architecture. |
| 3312 | 19237535 | This improved islet function was at least partially attributed to significant upregulation of the islet genes Irs1, SERCA, Ins1/2, and Glut2 in treated animals. |
| 3313 | 19237535 | The restoration of the Ins1/2 and Glut2 genes corresponded to a two- to threefold increase in the euchromatin marker histone H3 dimethyl-Lys4 at their respective promoters and was coincident with increased nuclear occupancy of the islet methyltransferase Set7/9. |
| 3314 | 19237535 | Consistent with this possibility, incubation of thapsigargin-treated INS-1 beta cells with the PPAR-gamma agonist resulted in the reduction of endoplasmic reticulum stress and restoration of Pdx1 protein levels and Set7/9 nuclear occupancy. |
| 3315 | 19237535 | We conclude that PPAR-gamma agonists exert a direct effect in diabetic islets to reduce endoplasmic reticulum stress and enhance Pdx1 levels, leading to favorable alterations of the islet gene chromatin architecture. |
| 3316 | 19245309 | Here, we report the derivation of insulin-producing cells from human or rat ADSC by transduction with the pancreatic duodenal homeobox 1 (Pdx1) gene. |
| 3317 | 19245309 | RT-PCR analyses showed that native ADSC expressed insulin, glucagon, and NeuroD genes that were up-regulated following Pdx1 transduction. |
| 3318 | 19245309 | Here, we report the derivation of insulin-producing cells from human or rat ADSC by transduction with the pancreatic duodenal homeobox 1 (Pdx1) gene. |
| 3319 | 19245309 | RT-PCR analyses showed that native ADSC expressed insulin, glucagon, and NeuroD genes that were up-regulated following Pdx1 transduction. |
| 3320 | 19255591 | Most of these insulin-producing cells co-expressed mature beta cell-specific markers such as NKX6-1 and PDX1, indicating a similar gene expression pattern to adult islet beta cells in vivo. |
| 3321 | 19255591 | In this study, we also demonstrated that EGF facilitates the expansion of PDX1-positive pancreatic progenitors. |
| 3322 | 19255591 | Most of these insulin-producing cells co-expressed mature beta cell-specific markers such as NKX6-1 and PDX1, indicating a similar gene expression pattern to adult islet beta cells in vivo. |
| 3323 | 19255591 | In this study, we also demonstrated that EGF facilitates the expansion of PDX1-positive pancreatic progenitors. |
| 3324 | 19264802 | The Krüppel-like zinc finger protein Glis3 directly and indirectly activates insulin gene transcription. |
| 3325 | 19264802 | Our aim was to examine the role of Glis3 in beta cells, specifically with regard to regulation of insulin gene transcription. |
| 3326 | 19264802 | We demonstrate that insulin 2 (Ins2) mRNA expression in rat insulinoma 832/13 cells is markedly increased by wild-type Glis3 overexpression, but not by the NDH1 mutant. |
| 3327 | 19264802 | Moreover, Glis3 physically and functionally interacts with Pdx1, MafA and NeuroD1 to modulate Ins2 promoter activity. |
| 3328 | 19264802 | Glis3 also may indirectly affect insulin promoter activity through upregulation of MafA and downregulation of Nkx6-1. |
| 3329 | 19264802 | This study uncovers a role of Glis3 for regulation of insulin gene expression and expands our understanding of its role in the beta cell. |
| 3330 | 19275670 | The roles of the PDZ-containing proteins bridge-1 and PDZD2 in the regulation of insulin production and pancreatic beta-cell mass. |
| 3331 | 19275670 | In a screen for interactors that regulate transcription factor function in pancreatic beta cells, we isolated two PDZ-containing proteins Bridge-1 (PSMD9) and PDZD2, which contain one and six PDZ domains, respectively. |
| 3332 | 19275670 | Bridge-1 interacts with both E12 and PDX-1 to stimulate insulin promoter activity. |
| 3333 | 19275670 | Interestingly, PDZD2 is proteolytically processed by caspase-3 to generate a carboxy-terminal secreted protein (sPDZD2) containing two PDZ domains. |
| 3334 | 19275670 | We propose that the PDZ domain proteins Bridge-1 and PDZD2 likely transduce signals that regulate insulin production, proliferation, and survival of pancreatic beta cells. |
| 3335 | 19379129 | Moreover, the presence of inductive factors in the Matrigel plus exendin-4 led to an increase in Pdx1 and endocrine genes, such as insulin, islet amyloid polypeptide, glucagon, the glucose transporter GLUT2, chromogranin A and the convertases PC1/3 and PC2 were also detected. |
| 3336 | 19379129 | We identified a population of PaSCs that express the ABCG2+ transporter and have the capacity to transdifferentiate into insulin-producing cells. |
| 3337 | 19393272 | Indeed, PDX-1 binding to the A3 element and NeuroD binding to the E1 element are crucial for insulin gene transcription. |
| 3338 | 19393272 | Recently, C1 element-binding transcription factor was identified as MafA, which is a basic-leucine zipper transcription factor and functions as a potent transactivator for the insulin gene. |
| 3339 | 19393272 | Under diabetic conditions, chronic hyperglycemia gradually deteriorates pancreatic beta-cell function, which is accompanied by decreased expression and/or DNA binding activities of MafA and PDX-1. |
| 3340 | 19393272 | Furthermore, MafA overexpression, together with PDX-1 and NeuroD, markedly induces insulin biosynthesis in various non-beta-cells and thereby is a useful tool to efficiently induce insulin-producing surrogate beta-cells. |
| 3341 | 19393272 | Indeed, PDX-1 binding to the A3 element and NeuroD binding to the E1 element are crucial for insulin gene transcription. |
| 3342 | 19393272 | Recently, C1 element-binding transcription factor was identified as MafA, which is a basic-leucine zipper transcription factor and functions as a potent transactivator for the insulin gene. |
| 3343 | 19393272 | Under diabetic conditions, chronic hyperglycemia gradually deteriorates pancreatic beta-cell function, which is accompanied by decreased expression and/or DNA binding activities of MafA and PDX-1. |
| 3344 | 19393272 | Furthermore, MafA overexpression, together with PDX-1 and NeuroD, markedly induces insulin biosynthesis in various non-beta-cells and thereby is a useful tool to efficiently induce insulin-producing surrogate beta-cells. |
| 3345 | 19393272 | Indeed, PDX-1 binding to the A3 element and NeuroD binding to the E1 element are crucial for insulin gene transcription. |
| 3346 | 19393272 | Recently, C1 element-binding transcription factor was identified as MafA, which is a basic-leucine zipper transcription factor and functions as a potent transactivator for the insulin gene. |
| 3347 | 19393272 | Under diabetic conditions, chronic hyperglycemia gradually deteriorates pancreatic beta-cell function, which is accompanied by decreased expression and/or DNA binding activities of MafA and PDX-1. |
| 3348 | 19393272 | Furthermore, MafA overexpression, together with PDX-1 and NeuroD, markedly induces insulin biosynthesis in various non-beta-cells and thereby is a useful tool to efficiently induce insulin-producing surrogate beta-cells. |
| 3349 | 19487809 | Heterozygous mutations in the gene encoding the pancreatic homeodomain transcription factor pancreatic duodenal homeobox 1 (PDX1) are associated with maturity onset diabetes of the young, type 4 (MODY4) and type 2 diabetes. |
| 3350 | 19487809 | Pdx1 governs the early embryonic development of the pancreas and the later differentiation of the insulin-producing islet beta cells of the endocrine compartment. |
| 3351 | 19487809 | During development, Pdx1 occupies an evolutionarily conserved enhancer region of Ngn3 and interacts with the transcription factor one cut homeobox 1 (Hnf6) to activate this enhancer. |
| 3352 | 19487809 | Furthermore, mRNA levels of all 4 members of the transcription factor network that regulates Ngn3 expression, SRY-box containing gene 9 (Sox9), Hnf6, Hnf1b, and forkhead box A2 (Foxa2), were decreased in homozygous mice. |
| 3353 | 19487809 | Pdx1 also occupied regulatory sequences in Foxa2 and Hnf1b. |
| 3354 | 19487809 | Heterozygous mutations in the gene encoding the pancreatic homeodomain transcription factor pancreatic duodenal homeobox 1 (PDX1) are associated with maturity onset diabetes of the young, type 4 (MODY4) and type 2 diabetes. |
| 3355 | 19487809 | Pdx1 governs the early embryonic development of the pancreas and the later differentiation of the insulin-producing islet beta cells of the endocrine compartment. |
| 3356 | 19487809 | During development, Pdx1 occupies an evolutionarily conserved enhancer region of Ngn3 and interacts with the transcription factor one cut homeobox 1 (Hnf6) to activate this enhancer. |
| 3357 | 19487809 | Furthermore, mRNA levels of all 4 members of the transcription factor network that regulates Ngn3 expression, SRY-box containing gene 9 (Sox9), Hnf6, Hnf1b, and forkhead box A2 (Foxa2), were decreased in homozygous mice. |
| 3358 | 19487809 | Pdx1 also occupied regulatory sequences in Foxa2 and Hnf1b. |
| 3359 | 19487809 | Heterozygous mutations in the gene encoding the pancreatic homeodomain transcription factor pancreatic duodenal homeobox 1 (PDX1) are associated with maturity onset diabetes of the young, type 4 (MODY4) and type 2 diabetes. |
| 3360 | 19487809 | Pdx1 governs the early embryonic development of the pancreas and the later differentiation of the insulin-producing islet beta cells of the endocrine compartment. |
| 3361 | 19487809 | During development, Pdx1 occupies an evolutionarily conserved enhancer region of Ngn3 and interacts with the transcription factor one cut homeobox 1 (Hnf6) to activate this enhancer. |
| 3362 | 19487809 | Furthermore, mRNA levels of all 4 members of the transcription factor network that regulates Ngn3 expression, SRY-box containing gene 9 (Sox9), Hnf6, Hnf1b, and forkhead box A2 (Foxa2), were decreased in homozygous mice. |
| 3363 | 19487809 | Pdx1 also occupied regulatory sequences in Foxa2 and Hnf1b. |
| 3364 | 19487809 | Heterozygous mutations in the gene encoding the pancreatic homeodomain transcription factor pancreatic duodenal homeobox 1 (PDX1) are associated with maturity onset diabetes of the young, type 4 (MODY4) and type 2 diabetes. |
| 3365 | 19487809 | Pdx1 governs the early embryonic development of the pancreas and the later differentiation of the insulin-producing islet beta cells of the endocrine compartment. |
| 3366 | 19487809 | During development, Pdx1 occupies an evolutionarily conserved enhancer region of Ngn3 and interacts with the transcription factor one cut homeobox 1 (Hnf6) to activate this enhancer. |
| 3367 | 19487809 | Furthermore, mRNA levels of all 4 members of the transcription factor network that regulates Ngn3 expression, SRY-box containing gene 9 (Sox9), Hnf6, Hnf1b, and forkhead box A2 (Foxa2), were decreased in homozygous mice. |
| 3368 | 19487809 | Pdx1 also occupied regulatory sequences in Foxa2 and Hnf1b. |
| 3369 | 19496967 | Permanent neonatal diabetes mellitus is a rare disorder known to be caused by activating mutations in KCNJ11 or ABCC8, inactivating mutations in INS, or very rarely in GCK or insulin promotor factor-1 (IPF-1) genes. |
| 3370 | 19544426 | Subsequent single-cell cloning resulted in a homogeneous cell population with a CD29(+)CD44(+)Sca-1(+) surface antigen expression profile. |
| 3371 | 19544426 | Our stage-specific approach successfully differentiated mesodermic mE-ASCs into definitive endoderm (cells expressing Sox17, Foxa2, GATA-4, and cytokeratin [CK]-19), then into pancreatic endoderm (cells expressing pancreatic and duodenal homeobox [PDX]-1, Ngn3, NeuroD, Pax4, and glucose transporter 2), and finally into cells expressing pancreatic hormones (insulin, glucagon, somatostatin). |
| 3372 | 19550075 | Administration of conophylline and betacellulin-delta4 increases the beta-cell mass in neonatal streptozotocin-treated rats. |
| 3373 | 19550075 | The beta-cell mass and the insulin content of the pancreas were significantly increased in the CnP group and delta4 group. |
| 3374 | 19550075 | CnP+BTCdelta4 significantly increased the number of PDX-1-positive ductal cells and the number of insulin/BrdU double-positive ductal cells. |
| 3375 | 19561381 | At 1 wk after HBT, asides from hepatic expression of insulin, the diabetic mice transfected with pcDNA-Pdx1 had a significantly lower sugar (211 +/- 61.6 vs. 413 +/- 62 mg/dL; p = 0.002) level than those transfected with pcDNA; however, the difference diminished afterward. |
| 3376 | 19576699 | An impairment of glucose-stimulated insulin secretion--reflecting decreased glucokinase expression--and a moderate decrease in beta cell mass attributable to increased apoptosis, constitute the key features of beta cell failure in type 2 diabetes. |
| 3377 | 19576699 | Oxidant-provoked JNK activation induces nuclear export of the PDX-1 transcription factor, required for expression of glucokinase and other beta cell proteins. |
| 3378 | 19604517 | Gestational high-fat programming impairs insulin release and reduces Pdx-1 and glucokinase immunoreactivity in neonatal Wistar rats. |
| 3379 | 19604517 | The aim of this study was to determine whether these changes were attributed to impaired insulin release and altered immunoreactivity of Pdx-1, glucokinase (GK), and glucose transporter (GLUT)-2 in high-fat-programmed neonates. |
| 3380 | 19604517 | No significant differences were found in Pdx-1, GK, or GLUT-2 messenger RNA expression. |
| 3381 | 19604517 | In HFG neonates, immunoreactivity of both Pdx-1 and GK was significantly reduced, with a nonsignificant reduction in GLUT-2. |
| 3382 | 19604517 | Gestational high-fat programming impairs insulin release and reduces Pdx-1 and GK immunoreactivity. |
| 3383 | 19604517 | Gestational high-fat programming impairs insulin release and reduces Pdx-1 and glucokinase immunoreactivity in neonatal Wistar rats. |
| 3384 | 19604517 | The aim of this study was to determine whether these changes were attributed to impaired insulin release and altered immunoreactivity of Pdx-1, glucokinase (GK), and glucose transporter (GLUT)-2 in high-fat-programmed neonates. |
| 3385 | 19604517 | No significant differences were found in Pdx-1, GK, or GLUT-2 messenger RNA expression. |
| 3386 | 19604517 | In HFG neonates, immunoreactivity of both Pdx-1 and GK was significantly reduced, with a nonsignificant reduction in GLUT-2. |
| 3387 | 19604517 | Gestational high-fat programming impairs insulin release and reduces Pdx-1 and GK immunoreactivity. |
| 3388 | 19604517 | Gestational high-fat programming impairs insulin release and reduces Pdx-1 and glucokinase immunoreactivity in neonatal Wistar rats. |
| 3389 | 19604517 | The aim of this study was to determine whether these changes were attributed to impaired insulin release and altered immunoreactivity of Pdx-1, glucokinase (GK), and glucose transporter (GLUT)-2 in high-fat-programmed neonates. |
| 3390 | 19604517 | No significant differences were found in Pdx-1, GK, or GLUT-2 messenger RNA expression. |
| 3391 | 19604517 | In HFG neonates, immunoreactivity of both Pdx-1 and GK was significantly reduced, with a nonsignificant reduction in GLUT-2. |
| 3392 | 19604517 | Gestational high-fat programming impairs insulin release and reduces Pdx-1 and GK immunoreactivity. |
| 3393 | 19604517 | Gestational high-fat programming impairs insulin release and reduces Pdx-1 and glucokinase immunoreactivity in neonatal Wistar rats. |
| 3394 | 19604517 | The aim of this study was to determine whether these changes were attributed to impaired insulin release and altered immunoreactivity of Pdx-1, glucokinase (GK), and glucose transporter (GLUT)-2 in high-fat-programmed neonates. |
| 3395 | 19604517 | No significant differences were found in Pdx-1, GK, or GLUT-2 messenger RNA expression. |
| 3396 | 19604517 | In HFG neonates, immunoreactivity of both Pdx-1 and GK was significantly reduced, with a nonsignificant reduction in GLUT-2. |
| 3397 | 19604517 | Gestational high-fat programming impairs insulin release and reduces Pdx-1 and GK immunoreactivity. |
| 3398 | 19604517 | Gestational high-fat programming impairs insulin release and reduces Pdx-1 and glucokinase immunoreactivity in neonatal Wistar rats. |
| 3399 | 19604517 | The aim of this study was to determine whether these changes were attributed to impaired insulin release and altered immunoreactivity of Pdx-1, glucokinase (GK), and glucose transporter (GLUT)-2 in high-fat-programmed neonates. |
| 3400 | 19604517 | No significant differences were found in Pdx-1, GK, or GLUT-2 messenger RNA expression. |
| 3401 | 19604517 | In HFG neonates, immunoreactivity of both Pdx-1 and GK was significantly reduced, with a nonsignificant reduction in GLUT-2. |
| 3402 | 19604517 | Gestational high-fat programming impairs insulin release and reduces Pdx-1 and GK immunoreactivity. |
| 3403 | 19608613 | Transcription factors know to regulate pancreas formation, pancreatic duodenal homeobox factor 1, neurogenin 3, NKX2-2, and NKX6-1, which were expressed in the appropriate spatial and temporal pattern to coordinate pancreatic bud outgrowth and direct endocrine cell specification in sheep. |
| 3404 | 19608613 | Immunofluorescence staining of the developing pancreas was used to co-localize insulin and epithelial proteins (cytokeratin, E-cadherin, and beta-catenin) or insulin and a mesenchymal protein (vimentin). |
| 3405 | 19610036 | Apoptosis was inferred by caspase-3 protein expression and caspase-3 activity and changes in Bcl-2 mRNA. |
| 3406 | 19610036 | RT-PCR was used to analyse PDX-1, insulin and UCP-2 mRNA expression in RINm5F beta-cells and insulin levels were quantified from the cell culture supernatant. |
| 3407 | 19610036 | Gallic acid dose-dependently increased insulin secretion in RINm5F beta-cells and upregulated mRNA of PDX-1 and insulin. |
| 3408 | 19610036 | Apoptosis was inferred by caspase-3 protein expression and caspase-3 activity and changes in Bcl-2 mRNA. |
| 3409 | 19610036 | RT-PCR was used to analyse PDX-1, insulin and UCP-2 mRNA expression in RINm5F beta-cells and insulin levels were quantified from the cell culture supernatant. |
| 3410 | 19610036 | Gallic acid dose-dependently increased insulin secretion in RINm5F beta-cells and upregulated mRNA of PDX-1 and insulin. |
| 3411 | 19651901 | The nucleosome binding protein HMGN3 modulates the transcription profile of pancreatic beta cells and affects insulin secretion. |
| 3412 | 19651901 | We now report that HMGN3, a nuclear protein that binds to nucleosomes and affects chromatin function, is highly expressed in beta cells and that in mice, loss of HMGN3 impairs glucose-stimulated insulin secretion and leads to a diabetic phenotype. |
| 3413 | 19651901 | In pancreatic beta cells, loss of HMGN3 affects the transcription of several genes involved in glucose-stimulated insulin secretion, including that of the Glut2 glucose transporter. |
| 3414 | 19651901 | Chromatin immunoprecipitation reveals that HMGN3 and the transcription factor PDX1 mutually reinforce their specific binding to the chromatin in the promoter of the Glut2 gene, thereby regulating GLUT2 protein levels in pancreatic islets and in beta cells. |
| 3415 | 19654319 | Increased autophagy was present in pancreatic islets from Pdx1(+/-) mice with reduced insulin secretion and beta cell mass. |
| 3416 | 19654319 | The in vivo effects of reduced autophagy were studied by crossing Pdx1(+/-) mice to Becn1(+/-) mice. |
| 3417 | 19654319 | After 1 week on a high fat diet, 4-week-old Pdx1(+/-) Becn1(+/-) mice showed normal glucose tolerance, preserved beta cell function, and increased beta cell mass compared with Pdx1(+/-) mice. |
| 3418 | 19654319 | Increased autophagy was present in pancreatic islets from Pdx1(+/-) mice with reduced insulin secretion and beta cell mass. |
| 3419 | 19654319 | The in vivo effects of reduced autophagy were studied by crossing Pdx1(+/-) mice to Becn1(+/-) mice. |
| 3420 | 19654319 | After 1 week on a high fat diet, 4-week-old Pdx1(+/-) Becn1(+/-) mice showed normal glucose tolerance, preserved beta cell function, and increased beta cell mass compared with Pdx1(+/-) mice. |
| 3421 | 19654319 | Increased autophagy was present in pancreatic islets from Pdx1(+/-) mice with reduced insulin secretion and beta cell mass. |
| 3422 | 19654319 | The in vivo effects of reduced autophagy were studied by crossing Pdx1(+/-) mice to Becn1(+/-) mice. |
| 3423 | 19654319 | After 1 week on a high fat diet, 4-week-old Pdx1(+/-) Becn1(+/-) mice showed normal glucose tolerance, preserved beta cell function, and increased beta cell mass compared with Pdx1(+/-) mice. |
| 3424 | 19656489 | PDX1 deficiency causes mitochondrial dysfunction and defective insulin secretion through TFAM suppression. |
| 3425 | 19656489 | Islet transduction with dominant-negative Pdx1 (RIPDN79PDX1) impairs mitochondrial metabolism and glucose-stimulated insulin secretion (GSIS). |
| 3426 | 19656489 | Herein, we show that Pdx1 suppression in adult mice reduces islet TFAM expression coinciding with hyperglycemia. |
| 3427 | 19656489 | We define TFAM as a direct target of Pdx1 both in rat INS1 cells and human islets. |
| 3428 | 19656489 | Adenoviral overexpression of TFAM along with RIPDN79PDX1 in isolated rat islets rescued mitochondrial DNA (mtDNA) copy number and restored respiratory chain activity as well as glucose-induced ATP synthesis and insulin secretion. |
| 3429 | 19656489 | Thus, the genetic control by the beta cell-specific factor Pdx1 of the ubiquitous gene TFAM maintains beta cell mtDNA vital for ATP production and normal GSIS. |
| 3430 | 19656489 | PDX1 deficiency causes mitochondrial dysfunction and defective insulin secretion through TFAM suppression. |
| 3431 | 19656489 | Islet transduction with dominant-negative Pdx1 (RIPDN79PDX1) impairs mitochondrial metabolism and glucose-stimulated insulin secretion (GSIS). |
| 3432 | 19656489 | Herein, we show that Pdx1 suppression in adult mice reduces islet TFAM expression coinciding with hyperglycemia. |
| 3433 | 19656489 | We define TFAM as a direct target of Pdx1 both in rat INS1 cells and human islets. |
| 3434 | 19656489 | Adenoviral overexpression of TFAM along with RIPDN79PDX1 in isolated rat islets rescued mitochondrial DNA (mtDNA) copy number and restored respiratory chain activity as well as glucose-induced ATP synthesis and insulin secretion. |
| 3435 | 19656489 | Thus, the genetic control by the beta cell-specific factor Pdx1 of the ubiquitous gene TFAM maintains beta cell mtDNA vital for ATP production and normal GSIS. |
| 3436 | 19656489 | PDX1 deficiency causes mitochondrial dysfunction and defective insulin secretion through TFAM suppression. |
| 3437 | 19656489 | Islet transduction with dominant-negative Pdx1 (RIPDN79PDX1) impairs mitochondrial metabolism and glucose-stimulated insulin secretion (GSIS). |
| 3438 | 19656489 | Herein, we show that Pdx1 suppression in adult mice reduces islet TFAM expression coinciding with hyperglycemia. |
| 3439 | 19656489 | We define TFAM as a direct target of Pdx1 both in rat INS1 cells and human islets. |
| 3440 | 19656489 | Adenoviral overexpression of TFAM along with RIPDN79PDX1 in isolated rat islets rescued mitochondrial DNA (mtDNA) copy number and restored respiratory chain activity as well as glucose-induced ATP synthesis and insulin secretion. |
| 3441 | 19656489 | Thus, the genetic control by the beta cell-specific factor Pdx1 of the ubiquitous gene TFAM maintains beta cell mtDNA vital for ATP production and normal GSIS. |
| 3442 | 19656489 | PDX1 deficiency causes mitochondrial dysfunction and defective insulin secretion through TFAM suppression. |
| 3443 | 19656489 | Islet transduction with dominant-negative Pdx1 (RIPDN79PDX1) impairs mitochondrial metabolism and glucose-stimulated insulin secretion (GSIS). |
| 3444 | 19656489 | Herein, we show that Pdx1 suppression in adult mice reduces islet TFAM expression coinciding with hyperglycemia. |
| 3445 | 19656489 | We define TFAM as a direct target of Pdx1 both in rat INS1 cells and human islets. |
| 3446 | 19656489 | Adenoviral overexpression of TFAM along with RIPDN79PDX1 in isolated rat islets rescued mitochondrial DNA (mtDNA) copy number and restored respiratory chain activity as well as glucose-induced ATP synthesis and insulin secretion. |
| 3447 | 19656489 | Thus, the genetic control by the beta cell-specific factor Pdx1 of the ubiquitous gene TFAM maintains beta cell mtDNA vital for ATP production and normal GSIS. |
| 3448 | 19656489 | PDX1 deficiency causes mitochondrial dysfunction and defective insulin secretion through TFAM suppression. |
| 3449 | 19656489 | Islet transduction with dominant-negative Pdx1 (RIPDN79PDX1) impairs mitochondrial metabolism and glucose-stimulated insulin secretion (GSIS). |
| 3450 | 19656489 | Herein, we show that Pdx1 suppression in adult mice reduces islet TFAM expression coinciding with hyperglycemia. |
| 3451 | 19656489 | We define TFAM as a direct target of Pdx1 both in rat INS1 cells and human islets. |
| 3452 | 19656489 | Adenoviral overexpression of TFAM along with RIPDN79PDX1 in isolated rat islets rescued mitochondrial DNA (mtDNA) copy number and restored respiratory chain activity as well as glucose-induced ATP synthesis and insulin secretion. |
| 3453 | 19656489 | Thus, the genetic control by the beta cell-specific factor Pdx1 of the ubiquitous gene TFAM maintains beta cell mtDNA vital for ATP production and normal GSIS. |
| 3454 | 19667185 | We found that BLK--a nonreceptor tyrosine-kinase of the src family of proto-oncogenes--is expressed in beta-cells where it enhances insulin synthesis and secretion in response to glucose by up-regulating transcription factors Pdx1 and Nkx6.1. |
| 3455 | 19689288 | Combination of MafA, PDX-1 and NeuroD is a useful tool to efficiently induce insulin-producing surrogate beta-cells. |
| 3456 | 19689288 | MafA, PDX-1 and NeuroD directly bind to the insulin gene promoter and function as very important transcription factors in pancreatic beta-cell differentiation and mature beta-cell function. |
| 3457 | 19689288 | The combination of MafA, PDX-1 and NeuroD markedly induces insulin biosynthesis in various non-beta-cells and thereby is a useful tool to efficiently induce insulin-producing surrogate beta-cells. |
| 3458 | 19689288 | Combination of MafA, PDX-1 and NeuroD is a useful tool to efficiently induce insulin-producing surrogate beta-cells. |
| 3459 | 19689288 | MafA, PDX-1 and NeuroD directly bind to the insulin gene promoter and function as very important transcription factors in pancreatic beta-cell differentiation and mature beta-cell function. |
| 3460 | 19689288 | The combination of MafA, PDX-1 and NeuroD markedly induces insulin biosynthesis in various non-beta-cells and thereby is a useful tool to efficiently induce insulin-producing surrogate beta-cells. |
| 3461 | 19689288 | Combination of MafA, PDX-1 and NeuroD is a useful tool to efficiently induce insulin-producing surrogate beta-cells. |
| 3462 | 19689288 | MafA, PDX-1 and NeuroD directly bind to the insulin gene promoter and function as very important transcription factors in pancreatic beta-cell differentiation and mature beta-cell function. |
| 3463 | 19689288 | The combination of MafA, PDX-1 and NeuroD markedly induces insulin biosynthesis in various non-beta-cells and thereby is a useful tool to efficiently induce insulin-producing surrogate beta-cells. |
| 3464 | 19729673 | Pancreata of euglycemic mice showed histological evidence of beta cell regeneration and expression of pancreas and duodenum transcription factor-1 (PDX-1) and neurogenin 3 (Ngn3) in ductal epithelium. |
| 3465 | 19757377 | Pdx1-transfected adipose tissue-derived stem cells differentiate into insulin-producing cells in vivo and reduce hyperglycemia in diabetic mice. |
| 3466 | 19757377 | Insulin-dependent diabetes mellitus (IDDM) is characterized by the rapid development of potentially severe metabolic abnormalities resulting from insulin deficiency. |
| 3467 | 19757377 | The transplantation of insulin-producing cells is a promising approach for the treatment of IDDM. |
| 3468 | 19757377 | The transcription factor pancreatic duodenal homeobox 1 (Pdx1) plays an important role in the differentiation of pancreatic beta cells. |
| 3469 | 19757377 | STZ-treated mice transplanted with Pdx1-transduced ASCs (Pdx1-ASCs) showed significantly decreased blood glucose levels and increased survival, when compared with control mice. |
| 3470 | 19757377 | While stable expression of Pdx1 in ASCs did not induce the pancreatic phenotype in vitro in our experiment, the transplanted stem cells became engrafted in the pancreas, wherein they expressed insulin and C-peptide, which is a marker of insulin-producing cells. |
| 3471 | 19757377 | Pdx1-transfected adipose tissue-derived stem cells differentiate into insulin-producing cells in vivo and reduce hyperglycemia in diabetic mice. |
| 3472 | 19757377 | Insulin-dependent diabetes mellitus (IDDM) is characterized by the rapid development of potentially severe metabolic abnormalities resulting from insulin deficiency. |
| 3473 | 19757377 | The transplantation of insulin-producing cells is a promising approach for the treatment of IDDM. |
| 3474 | 19757377 | The transcription factor pancreatic duodenal homeobox 1 (Pdx1) plays an important role in the differentiation of pancreatic beta cells. |
| 3475 | 19757377 | STZ-treated mice transplanted with Pdx1-transduced ASCs (Pdx1-ASCs) showed significantly decreased blood glucose levels and increased survival, when compared with control mice. |
| 3476 | 19757377 | While stable expression of Pdx1 in ASCs did not induce the pancreatic phenotype in vitro in our experiment, the transplanted stem cells became engrafted in the pancreas, wherein they expressed insulin and C-peptide, which is a marker of insulin-producing cells. |
| 3477 | 19757377 | Pdx1-transfected adipose tissue-derived stem cells differentiate into insulin-producing cells in vivo and reduce hyperglycemia in diabetic mice. |
| 3478 | 19757377 | Insulin-dependent diabetes mellitus (IDDM) is characterized by the rapid development of potentially severe metabolic abnormalities resulting from insulin deficiency. |
| 3479 | 19757377 | The transplantation of insulin-producing cells is a promising approach for the treatment of IDDM. |
| 3480 | 19757377 | The transcription factor pancreatic duodenal homeobox 1 (Pdx1) plays an important role in the differentiation of pancreatic beta cells. |
| 3481 | 19757377 | STZ-treated mice transplanted with Pdx1-transduced ASCs (Pdx1-ASCs) showed significantly decreased blood glucose levels and increased survival, when compared with control mice. |
| 3482 | 19757377 | While stable expression of Pdx1 in ASCs did not induce the pancreatic phenotype in vitro in our experiment, the transplanted stem cells became engrafted in the pancreas, wherein they expressed insulin and C-peptide, which is a marker of insulin-producing cells. |
| 3483 | 19757377 | Pdx1-transfected adipose tissue-derived stem cells differentiate into insulin-producing cells in vivo and reduce hyperglycemia in diabetic mice. |
| 3484 | 19757377 | Insulin-dependent diabetes mellitus (IDDM) is characterized by the rapid development of potentially severe metabolic abnormalities resulting from insulin deficiency. |
| 3485 | 19757377 | The transplantation of insulin-producing cells is a promising approach for the treatment of IDDM. |
| 3486 | 19757377 | The transcription factor pancreatic duodenal homeobox 1 (Pdx1) plays an important role in the differentiation of pancreatic beta cells. |
| 3487 | 19757377 | STZ-treated mice transplanted with Pdx1-transduced ASCs (Pdx1-ASCs) showed significantly decreased blood glucose levels and increased survival, when compared with control mice. |
| 3488 | 19757377 | While stable expression of Pdx1 in ASCs did not induce the pancreatic phenotype in vitro in our experiment, the transplanted stem cells became engrafted in the pancreas, wherein they expressed insulin and C-peptide, which is a marker of insulin-producing cells. |
| 3489 | 19770784 | Pdx-1 regulation of the INGAP promoter involves sequestration of NeuroD into a non-DNA-binding complex. |
| 3490 | 19775518 | The HN#13 cells, which had the highest expression of insulin mRNA after induction, expressed PDX-1 transcription factor, glucagon-like peptide-1 (GLP-1) receptor, and cytokeratin-19 (duct-like cells). |
| 3491 | 19775518 | Exendin-4 treatment and transduction of PDX-1 and NeuroD proteins by protein transduction technology in HN#13 cells induced insulin and pancreas-related gene expression. |
| 3492 | 19775518 | The HN#13 cells, which had the highest expression of insulin mRNA after induction, expressed PDX-1 transcription factor, glucagon-like peptide-1 (GLP-1) receptor, and cytokeratin-19 (duct-like cells). |
| 3493 | 19775518 | Exendin-4 treatment and transduction of PDX-1 and NeuroD proteins by protein transduction technology in HN#13 cells induced insulin and pancreas-related gene expression. |
| 3494 | 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. |
| 3495 | 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. |
| 3496 | 19785038 | Coexpression of all three transcription factors had little effect on INS mRNA levels but unexpectedly increased GCG mRNA at least 100,000-fold. |
| 3497 | 19785038 | In contrast to the endogenous promoter, an exogenous rat INS promoter was activated by expression of Pdx1 and Mafa in hIPCs. |
| 3498 | 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. |
| 3499 | 19785038 | Furthermore, the INS gene was found to be less accessible to micrococcal nuclease digestion than the GCG gene. |
| 3500 | 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. |
| 3501 | 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. |
| 3502 | 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. |
| 3503 | 19785038 | Coexpression of all three transcription factors had little effect on INS mRNA levels but unexpectedly increased GCG mRNA at least 100,000-fold. |
| 3504 | 19785038 | In contrast to the endogenous promoter, an exogenous rat INS promoter was activated by expression of Pdx1 and Mafa in hIPCs. |
| 3505 | 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. |
| 3506 | 19785038 | Furthermore, the INS gene was found to be less accessible to micrococcal nuclease digestion than the GCG gene. |
| 3507 | 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. |
| 3508 | 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. |
| 3509 | 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. |
| 3510 | 19785038 | Coexpression of all three transcription factors had little effect on INS mRNA levels but unexpectedly increased GCG mRNA at least 100,000-fold. |
| 3511 | 19785038 | In contrast to the endogenous promoter, an exogenous rat INS promoter was activated by expression of Pdx1 and Mafa in hIPCs. |
| 3512 | 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. |
| 3513 | 19785038 | Furthermore, the INS gene was found to be less accessible to micrococcal nuclease digestion than the GCG gene. |
| 3514 | 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. |
| 3515 | 19805515 | Transcription factor Glis3, a novel critical player in the regulation of pancreatic beta-cell development and insulin gene expression. |
| 3516 | 19805515 | In this study, we report that the Krüppel-like zinc finger transcription factor Gli-similar 3 (Glis3) is induced during the secondary transition of pancreatic development, a stage of cell lineage specification and extensive patterning, and that Glis3(zf/zf) mutant mice develop neonatal diabetes, evidenced by hyperglycemia and hypoinsulinemia. |
| 3517 | 19805515 | Gene expression profiling and immunofluorescent staining demonstrated that the expression of pancreatic hormones and several transcription factors important in endocrine cell development, including Ngn3, MafA, and Pdx1, were significantly decreased in the developing pancreata of Glis3(zf/zf) mutant mice. |
| 3518 | 19805515 | The population of pancreatic progenitors appears not to be greatly affected in Glis3(zf/zf) mutant mice; however, the number of neurogenin 3 (Ngn3)-positive endocrine cell progenitors is significantly reduced. |
| 3519 | 19805515 | In addition, we provide evidence that Glis3 regulates insulin gene expression through two Glis-binding sites in its proximal promoter, indicating that Glis3 also regulates beta-cell function. |
| 3520 | 19817786 | Pancreatic duodenal homeobox 1 (Pdx1) is a transcription factor that plays a central role in pancreatic beta-cell function and survival. |
| 3521 | 19817786 | Inhibition of insulin/insulin-like growth factor (Igf) signalling followed by reduced Pdx1 expression is a common pathway induced by the majority of the mechanisms in apoptotic beta-cells. |
| 3522 | 19817786 | Pancreatic duodenal homeobox 1 (Pdx1) is a transcription factor that plays a central role in pancreatic beta-cell function and survival. |
| 3523 | 19817786 | Inhibition of insulin/insulin-like growth factor (Igf) signalling followed by reduced Pdx1 expression is a common pathway induced by the majority of the mechanisms in apoptotic beta-cells. |
| 3524 | 19837872 | Forkhead box O1/pancreatic and duodenal homeobox 1 intracellular translocation is regulated by c-Jun N-terminal kinase and involved in prostaglandin E2-induced pancreatic beta-cell dysfunction. |
| 3525 | 19837872 | We found that PGE(2) time-dependently increased the c-Jun N-terminal kinase (JNK) pathway activity. |
| 3526 | 19837872 | JNK inhibition by the JNK-specific inhibitor SP600125 reversed PGE(2)-inhibited glucose-stimulated insulin secretion (GSIS). |
| 3527 | 19837872 | PGE(2) induced dephosphorylation of Akt and FOXO1, leading to nuclear localization and transactivation of FOXO1. |
| 3528 | 19837872 | Activation of FOXO1 induced nuclear exclusion but had no obvious effect on the whole-cell protein level of pancreatic and duodenal homeobox 1 (PDX1). |
| 3529 | 19837872 | In addition, we demonstrated that DN-JNK1 but not DN-JNK2 or CA-Akt abolished the PGE(2)-induced AP-1 luciferase reporter activity, whereas DN-JNK1 and CA-Akt but not DN-JNK2 reversed the effect of PGE(2) on FOXO1 transcriptional activity, and overexpression of DN-JNK1 rescued PGE(2)-impaired GSIS in mouse islets. |
| 3530 | 19837872 | PGE(2)-mediated JNK1 activation, through dephosphorylation of Akt and FOXO1, leads to nuclear accumulation of FOXO1 and nucleocytoplasmic shuttling of PDX1, finally resulting in defective GSIS in pancreatic beta-cells. |
| 3531 | 19837872 | Forkhead box O1/pancreatic and duodenal homeobox 1 intracellular translocation is regulated by c-Jun N-terminal kinase and involved in prostaglandin E2-induced pancreatic beta-cell dysfunction. |
| 3532 | 19837872 | We found that PGE(2) time-dependently increased the c-Jun N-terminal kinase (JNK) pathway activity. |
| 3533 | 19837872 | JNK inhibition by the JNK-specific inhibitor SP600125 reversed PGE(2)-inhibited glucose-stimulated insulin secretion (GSIS). |
| 3534 | 19837872 | PGE(2) induced dephosphorylation of Akt and FOXO1, leading to nuclear localization and transactivation of FOXO1. |
| 3535 | 19837872 | Activation of FOXO1 induced nuclear exclusion but had no obvious effect on the whole-cell protein level of pancreatic and duodenal homeobox 1 (PDX1). |
| 3536 | 19837872 | In addition, we demonstrated that DN-JNK1 but not DN-JNK2 or CA-Akt abolished the PGE(2)-induced AP-1 luciferase reporter activity, whereas DN-JNK1 and CA-Akt but not DN-JNK2 reversed the effect of PGE(2) on FOXO1 transcriptional activity, and overexpression of DN-JNK1 rescued PGE(2)-impaired GSIS in mouse islets. |
| 3537 | 19837872 | PGE(2)-mediated JNK1 activation, through dephosphorylation of Akt and FOXO1, leads to nuclear accumulation of FOXO1 and nucleocytoplasmic shuttling of PDX1, finally resulting in defective GSIS in pancreatic beta-cells. |
| 3538 | 19837872 | Forkhead box O1/pancreatic and duodenal homeobox 1 intracellular translocation is regulated by c-Jun N-terminal kinase and involved in prostaglandin E2-induced pancreatic beta-cell dysfunction. |
| 3539 | 19837872 | We found that PGE(2) time-dependently increased the c-Jun N-terminal kinase (JNK) pathway activity. |
| 3540 | 19837872 | JNK inhibition by the JNK-specific inhibitor SP600125 reversed PGE(2)-inhibited glucose-stimulated insulin secretion (GSIS). |
| 3541 | 19837872 | PGE(2) induced dephosphorylation of Akt and FOXO1, leading to nuclear localization and transactivation of FOXO1. |
| 3542 | 19837872 | Activation of FOXO1 induced nuclear exclusion but had no obvious effect on the whole-cell protein level of pancreatic and duodenal homeobox 1 (PDX1). |
| 3543 | 19837872 | In addition, we demonstrated that DN-JNK1 but not DN-JNK2 or CA-Akt abolished the PGE(2)-induced AP-1 luciferase reporter activity, whereas DN-JNK1 and CA-Akt but not DN-JNK2 reversed the effect of PGE(2) on FOXO1 transcriptional activity, and overexpression of DN-JNK1 rescued PGE(2)-impaired GSIS in mouse islets. |
| 3544 | 19837872 | PGE(2)-mediated JNK1 activation, through dephosphorylation of Akt and FOXO1, leads to nuclear accumulation of FOXO1 and nucleocytoplasmic shuttling of PDX1, finally resulting in defective GSIS in pancreatic beta-cells. |
| 3545 | 19843526 | MODY7 gene, KLF11, is a novel p300-dependent regulator of Pdx-1 (MODY4) transcription in pancreatic islet beta cells. |
| 3546 | 19843526 | Pdx-1 (pancreatic-duodenal homeobox-1), a MODY4 homeodomain transcription factor, serves as a master regulator in the pancreas because of its importance during organogenesis and in adult islet insulin-producing beta cell activity. |
| 3547 | 19843526 | Here, we show that KLF11, an SP/Krüppel-like (SP/KLF) transcription factor, mutated in French maturity onset diabetes of the young patients (MODY7), regulates Pdx-1 transcription in beta cells through two evolutionarily conserved GC-rich motifs in conserved Area II, a control region essential to islet beta cell-enriched expression. |
| 3548 | 19843526 | KLF11 specifically associates with Area II in chromatin immunoprecipitation assays, while preventing binding to GC1- and/or GC2-compromised Pdx1-driven reporter activity in beta cell lines. |
| 3549 | 19843526 | Mechanistically, we find that KLF11 interacts with the coactivator p300 via its zinc finger domain in vivo to mediate Pdx-1 activation. |
| 3550 | 19843526 | Furthermore, because KLF11 like most MODY-associated transcription factors uses p300, these data further support a role for this coactivator as a critical chromatin link in forms of type 2 diabetes. |
| 3551 | 19843526 | MODY7 gene, KLF11, is a novel p300-dependent regulator of Pdx-1 (MODY4) transcription in pancreatic islet beta cells. |
| 3552 | 19843526 | Pdx-1 (pancreatic-duodenal homeobox-1), a MODY4 homeodomain transcription factor, serves as a master regulator in the pancreas because of its importance during organogenesis and in adult islet insulin-producing beta cell activity. |
| 3553 | 19843526 | Here, we show that KLF11, an SP/Krüppel-like (SP/KLF) transcription factor, mutated in French maturity onset diabetes of the young patients (MODY7), regulates Pdx-1 transcription in beta cells through two evolutionarily conserved GC-rich motifs in conserved Area II, a control region essential to islet beta cell-enriched expression. |
| 3554 | 19843526 | KLF11 specifically associates with Area II in chromatin immunoprecipitation assays, while preventing binding to GC1- and/or GC2-compromised Pdx1-driven reporter activity in beta cell lines. |
| 3555 | 19843526 | Mechanistically, we find that KLF11 interacts with the coactivator p300 via its zinc finger domain in vivo to mediate Pdx-1 activation. |
| 3556 | 19843526 | Furthermore, because KLF11 like most MODY-associated transcription factors uses p300, these data further support a role for this coactivator as a critical chromatin link in forms of type 2 diabetes. |
| 3557 | 19843526 | MODY7 gene, KLF11, is a novel p300-dependent regulator of Pdx-1 (MODY4) transcription in pancreatic islet beta cells. |
| 3558 | 19843526 | Pdx-1 (pancreatic-duodenal homeobox-1), a MODY4 homeodomain transcription factor, serves as a master regulator in the pancreas because of its importance during organogenesis and in adult islet insulin-producing beta cell activity. |
| 3559 | 19843526 | Here, we show that KLF11, an SP/Krüppel-like (SP/KLF) transcription factor, mutated in French maturity onset diabetes of the young patients (MODY7), regulates Pdx-1 transcription in beta cells through two evolutionarily conserved GC-rich motifs in conserved Area II, a control region essential to islet beta cell-enriched expression. |
| 3560 | 19843526 | KLF11 specifically associates with Area II in chromatin immunoprecipitation assays, while preventing binding to GC1- and/or GC2-compromised Pdx1-driven reporter activity in beta cell lines. |
| 3561 | 19843526 | Mechanistically, we find that KLF11 interacts with the coactivator p300 via its zinc finger domain in vivo to mediate Pdx-1 activation. |
| 3562 | 19843526 | Furthermore, because KLF11 like most MODY-associated transcription factors uses p300, these data further support a role for this coactivator as a critical chromatin link in forms of type 2 diabetes. |
| 3563 | 19843526 | MODY7 gene, KLF11, is a novel p300-dependent regulator of Pdx-1 (MODY4) transcription in pancreatic islet beta cells. |
| 3564 | 19843526 | Pdx-1 (pancreatic-duodenal homeobox-1), a MODY4 homeodomain transcription factor, serves as a master regulator in the pancreas because of its importance during organogenesis and in adult islet insulin-producing beta cell activity. |
| 3565 | 19843526 | Here, we show that KLF11, an SP/Krüppel-like (SP/KLF) transcription factor, mutated in French maturity onset diabetes of the young patients (MODY7), regulates Pdx-1 transcription in beta cells through two evolutionarily conserved GC-rich motifs in conserved Area II, a control region essential to islet beta cell-enriched expression. |
| 3566 | 19843526 | KLF11 specifically associates with Area II in chromatin immunoprecipitation assays, while preventing binding to GC1- and/or GC2-compromised Pdx1-driven reporter activity in beta cell lines. |
| 3567 | 19843526 | Mechanistically, we find that KLF11 interacts with the coactivator p300 via its zinc finger domain in vivo to mediate Pdx-1 activation. |
| 3568 | 19843526 | Furthermore, because KLF11 like most MODY-associated transcription factors uses p300, these data further support a role for this coactivator as a critical chromatin link in forms of type 2 diabetes. |
| 3569 | 19843526 | MODY7 gene, KLF11, is a novel p300-dependent regulator of Pdx-1 (MODY4) transcription in pancreatic islet beta cells. |
| 3570 | 19843526 | Pdx-1 (pancreatic-duodenal homeobox-1), a MODY4 homeodomain transcription factor, serves as a master regulator in the pancreas because of its importance during organogenesis and in adult islet insulin-producing beta cell activity. |
| 3571 | 19843526 | Here, we show that KLF11, an SP/Krüppel-like (SP/KLF) transcription factor, mutated in French maturity onset diabetes of the young patients (MODY7), regulates Pdx-1 transcription in beta cells through two evolutionarily conserved GC-rich motifs in conserved Area II, a control region essential to islet beta cell-enriched expression. |
| 3572 | 19843526 | KLF11 specifically associates with Area II in chromatin immunoprecipitation assays, while preventing binding to GC1- and/or GC2-compromised Pdx1-driven reporter activity in beta cell lines. |
| 3573 | 19843526 | Mechanistically, we find that KLF11 interacts with the coactivator p300 via its zinc finger domain in vivo to mediate Pdx-1 activation. |
| 3574 | 19843526 | Furthermore, because KLF11 like most MODY-associated transcription factors uses p300, these data further support a role for this coactivator as a critical chromatin link in forms of type 2 diabetes. |
| 3575 | 19855005 | Heterozygous mutations in the gene encoding the beta cell transcription factor pancreatic duodenal homeobox 1 (Pdx1) are associated with both T2DM and maturity onset diabetes of the young (MODY4), and low levels of Pdx1 accompany beta cell dysfunction in experimental models of glucotoxicity and diabetes. |
| 3576 | 19855005 | Here, we find that Pdx1 is required for compensatory beta cell mass expansion in response to diet-induced insulin resistance through its roles in promoting beta cell survival and compensatory hypertrophy. |
| 3577 | 19855005 | These findings suggest that Pdx1 deficiency leads to a failure of beta cell compensation for insulin resistance at least in part by impairing critical functions of the ER. |
| 3578 | 19855005 | Heterozygous mutations in the gene encoding the beta cell transcription factor pancreatic duodenal homeobox 1 (Pdx1) are associated with both T2DM and maturity onset diabetes of the young (MODY4), and low levels of Pdx1 accompany beta cell dysfunction in experimental models of glucotoxicity and diabetes. |
| 3579 | 19855005 | Here, we find that Pdx1 is required for compensatory beta cell mass expansion in response to diet-induced insulin resistance through its roles in promoting beta cell survival and compensatory hypertrophy. |
| 3580 | 19855005 | These findings suggest that Pdx1 deficiency leads to a failure of beta cell compensation for insulin resistance at least in part by impairing critical functions of the ER. |
| 3581 | 19855005 | Heterozygous mutations in the gene encoding the beta cell transcription factor pancreatic duodenal homeobox 1 (Pdx1) are associated with both T2DM and maturity onset diabetes of the young (MODY4), and low levels of Pdx1 accompany beta cell dysfunction in experimental models of glucotoxicity and diabetes. |
| 3582 | 19855005 | Here, we find that Pdx1 is required for compensatory beta cell mass expansion in response to diet-induced insulin resistance through its roles in promoting beta cell survival and compensatory hypertrophy. |
| 3583 | 19855005 | These findings suggest that Pdx1 deficiency leads to a failure of beta cell compensation for insulin resistance at least in part by impairing critical functions of the ER. |
| 3584 | 19897925 | The rise in hyperplasia was associated with elevated IRS2 and PDX-1 expression in the islets. |
| 3585 | 19901909 | Pancreatic duodenal homeobox 1 (Pdx1) protein is a key transcription factor involved in the regulation of insulin gene expression that is expressed at high levels in the beta-cells of the pancreatic islets. |
| 3586 | 19965940 | Decreased IRS2 attenuated the phosphorylation of Akt and, subsequently, PDX-1 protein levels were lowered in olanzapine-treated rats. |
| 3587 | 20020058 | Importantly, the recovery efficiency of the p21-overexpressing mice from streptozotocin-induced diabetes was significantly higher than control mice, which is embodied by better physiological quality and earlier emergence of insulin expressing cells. |
| 3588 | 20020058 | Furthermore, in the islets of these streptozotocin-treated transgenic mice, we found a large population of proliferating cells which expressed pancreatic duodenal homeobox 1 (PDX1) but not markers of terminally differentiated cells. |
| 3589 | 20020058 | Transcription factors characteristic of early pancreatic development, such as Nkx2.2 and NeuroD1, and pancreatic progenitor markers, such as Ngn3 and c-Met, could also be detected in these islets. |
| 3590 | 20038945 | In this issue of Laboratory Investigation, Li et al propose the transcription factor Pancreatic and duodenal homeobox 1 (PDX-1) as a T1D autoantigen by demonstrating autoreactivity to this pancreas-specific protein in both the NOD mouse model and patients with T1D. |
| 3591 | 20038945 | Because of the known roles of PDX-1 in pancreatic development as well as beta cell maintenance and function, targeting of PDX-1 expressing cells may result in the elimination of not only beta cells but also the progenitor cells required for regeneration of insulin-producing cells. |
| 3592 | 20038945 | In this issue of Laboratory Investigation, Li et al propose the transcription factor Pancreatic and duodenal homeobox 1 (PDX-1) as a T1D autoantigen by demonstrating autoreactivity to this pancreas-specific protein in both the NOD mouse model and patients with T1D. |
| 3593 | 20038945 | Because of the known roles of PDX-1 in pancreatic development as well as beta cell maintenance and function, targeting of PDX-1 expressing cells may result in the elimination of not only beta cells but also the progenitor cells required for regeneration of insulin-producing cells. |
| 3594 | 20079600 | Conophylline increased the mRNA expression of PDX-1, neurogenin3, neuroD/Beta2, and insulin in ICC. |
| 3595 | 20082465 | Investigations included sequencing of GCK, ABCC8, IPF1, NEUROD1, PTF1A, HNF1B, INS, ISL1, NGN3, HHEX, G6PC2, TCF7L2, SOX4, FOXP3 (Patients 1 and 2), GATA4 and KCNJ11 genes (all three patients), but no mutations were found. |
| 3596 | 20092027 | Genetic analysis was negative for mutations of KCNJ11, 6q24, Glucokinase and IPF-1 genes. |
| 3597 | 20096455 | These have been well-characterised in the PR rat, where impaired insulin secretion is linked to epigenetic changes at the Pdx-1 promotor and reduced expression of this transcription factor. |
| 3598 | 20101199 | Histologic assessment was performed at PODs 3, 7, 14, 28, and 84 for the detection of von Willebrand factor (vWF), vascular endothelial growth factor (VEGF), insulin, cluster of differentiation-34, and pancreatic duodenal homeobox-1 (PDX-1) protein. |
| 3599 | 20156502 | Activation of the adiponectin receptors has a clear role in improving insulin resistance although conflicting evidence exists for its effects on pancreatic beta-cells. |
| 3600 | 20156502 | This study investigates the effects of two agonist regions of adiponectin on insulin secretion, gene expression, cell viability and cell signalling in the rat beta-cell line BRIN-BD11, as well as investigating the expression levels of adiponectin receptors (ADRs) in these cells. |
| 3601 | 20156502 | Cells were treated with globular adiponectin and adiponectin (15-36) +/-leptin to investigate cell viability, expression of key beta-cell genes and ERK1/2 activation. |
| 3602 | 20156502 | Both globular adiponectin and adiponectin (15-36) caused significant ERK1/2 dependent increases in cell viability. |
| 3603 | 20156502 | Leptin co-incubation attenuated adiponectin (15-36) but not globular adiponectin induced cell viability. |
| 3604 | 20156502 | Globular adiponectin, but not adiponectin (15-36), caused a significant 450% increase in PDX-1 expression and a 45% decrease in LPL expression. |
| 3605 | 20158571 | MafA promotes the reprogramming of placenta-derived multipotent stem cells into pancreatic islets-like and insulin+ cells. |
| 3606 | 20158571 | MafA is a pancreatic transcriptional factor that controls β-cell-specific transcription of the insulin gene. |
| 3607 | 20158571 | In this study, we investigate the role of MafA in placenta-derived multipotent stem cells (PDMSCs) that constitutively expressed Oct-4 and Nanog. |
| 3608 | 20158571 | Our results showed that overexpression of MafA in PDMSCs significantly up-regulated the expression of pancreatic development-related genes (Sox17, Foxa2, Pdx1 and Ngn3). |
| 3609 | 20158571 | MafA increased the expression levels of the mRNAs of NKx2.2, Glut2, insulin, glucagons and somatostatin, and further facilitated the differentiation of PDMSCs into insulin(+) cells. |
| 3610 | 20158571 | The glucose-stimulated responses to insulin and c-peptide production in MafA-overexpressing PDMSCs were significantly higher than in PDMSCs with vector control. |
| 3611 | 20158571 | Importantly, the expression of MafA in PDMSCs xenotransplanted into immunocompromised mice improved the restoration of blood insulin levels to control values and greatly prolonged the survival of graft cells in immunocompromised mice with STZ-induced diabetes. |
| 3612 | 20158571 | In summary, these data suggest that MafA plays a novel role in the reprogramming of stem cells into pancreatic β-progenitors, promotes the islet-like characteristics of PDMSCs, as well as functionally enhances insulin production to restore the regulation of blood glucose levels in transplanted grafts. |
| 3613 | 20217517 | Treatment with various growth factors such as GLP-1, BTC, HGF, and EGF and forced expression of beta-cell transcription factors such as Pdx-1, NeuroD, and MafA resulted in the regeneration of beta-cells in vivo. |
| 3614 | 20306305 | Expression of Pdx1 mediates differentiation from mesenchymal stem cells into insulin-producing cells. |
| 3615 | 20306305 | Pancreatic duodenal homeobox 1 (Pdx1) plays a key role in the differentiation of various non-β-cells into insulin-producing cells, but the potential mechanism remains to be clarified. |
| 3616 | 20306305 | The purpose of this study was to confirm that the expression of Pdx1 could mediate the differentiation of rat mesenchymal stem cells (MSCs) into insulin-producing cells and evaluate the potential molecular mechanisms in the process that Pdx1 activates transcription of insulin gene. |
| 3617 | 20306305 | In this study, glucose-stimulated insulin secretion was obviously detected in MSCs transfected with Pdx1 cDNA by insulin release assay and the islet-like structure formed in Pdx1-expressing MSCs was stained into black-red by dithizone, while the native MSCs were opposite. |
| 3618 | 20306305 | In addition, we uncovered the close relationships among the expression of Pdx1, insulin and Ngn3 genes, whose expression indicated parallel changes after high glucose challenge, and the fluctuation of Pdx1 and Ngn3 partly resulted in the unstable release of insulin. |
| 3619 | 20306305 | Taken together, these findings demonstrated that the effective role of Pdx1 gene in inducing insulin-producing cells, which may shuttle to the nucleoplasm of MSCs under high glucose, then initiate the expression of native transcription factors Ngn3 and recruit other proteins, resulting in transactivation of the relevant genes including insulin and generation of β cell phenotype. |
| 3620 | 20306305 | Expression of Pdx1 mediates differentiation from mesenchymal stem cells into insulin-producing cells. |
| 3621 | 20306305 | Pancreatic duodenal homeobox 1 (Pdx1) plays a key role in the differentiation of various non-β-cells into insulin-producing cells, but the potential mechanism remains to be clarified. |
| 3622 | 20306305 | The purpose of this study was to confirm that the expression of Pdx1 could mediate the differentiation of rat mesenchymal stem cells (MSCs) into insulin-producing cells and evaluate the potential molecular mechanisms in the process that Pdx1 activates transcription of insulin gene. |
| 3623 | 20306305 | In this study, glucose-stimulated insulin secretion was obviously detected in MSCs transfected with Pdx1 cDNA by insulin release assay and the islet-like structure formed in Pdx1-expressing MSCs was stained into black-red by dithizone, while the native MSCs were opposite. |
| 3624 | 20306305 | In addition, we uncovered the close relationships among the expression of Pdx1, insulin and Ngn3 genes, whose expression indicated parallel changes after high glucose challenge, and the fluctuation of Pdx1 and Ngn3 partly resulted in the unstable release of insulin. |
| 3625 | 20306305 | Taken together, these findings demonstrated that the effective role of Pdx1 gene in inducing insulin-producing cells, which may shuttle to the nucleoplasm of MSCs under high glucose, then initiate the expression of native transcription factors Ngn3 and recruit other proteins, resulting in transactivation of the relevant genes including insulin and generation of β cell phenotype. |
| 3626 | 20306305 | Expression of Pdx1 mediates differentiation from mesenchymal stem cells into insulin-producing cells. |
| 3627 | 20306305 | Pancreatic duodenal homeobox 1 (Pdx1) plays a key role in the differentiation of various non-β-cells into insulin-producing cells, but the potential mechanism remains to be clarified. |
| 3628 | 20306305 | The purpose of this study was to confirm that the expression of Pdx1 could mediate the differentiation of rat mesenchymal stem cells (MSCs) into insulin-producing cells and evaluate the potential molecular mechanisms in the process that Pdx1 activates transcription of insulin gene. |
| 3629 | 20306305 | In this study, glucose-stimulated insulin secretion was obviously detected in MSCs transfected with Pdx1 cDNA by insulin release assay and the islet-like structure formed in Pdx1-expressing MSCs was stained into black-red by dithizone, while the native MSCs were opposite. |
| 3630 | 20306305 | In addition, we uncovered the close relationships among the expression of Pdx1, insulin and Ngn3 genes, whose expression indicated parallel changes after high glucose challenge, and the fluctuation of Pdx1 and Ngn3 partly resulted in the unstable release of insulin. |
| 3631 | 20306305 | Taken together, these findings demonstrated that the effective role of Pdx1 gene in inducing insulin-producing cells, which may shuttle to the nucleoplasm of MSCs under high glucose, then initiate the expression of native transcription factors Ngn3 and recruit other proteins, resulting in transactivation of the relevant genes including insulin and generation of β cell phenotype. |
| 3632 | 20306305 | Expression of Pdx1 mediates differentiation from mesenchymal stem cells into insulin-producing cells. |
| 3633 | 20306305 | Pancreatic duodenal homeobox 1 (Pdx1) plays a key role in the differentiation of various non-β-cells into insulin-producing cells, but the potential mechanism remains to be clarified. |
| 3634 | 20306305 | The purpose of this study was to confirm that the expression of Pdx1 could mediate the differentiation of rat mesenchymal stem cells (MSCs) into insulin-producing cells and evaluate the potential molecular mechanisms in the process that Pdx1 activates transcription of insulin gene. |
| 3635 | 20306305 | In this study, glucose-stimulated insulin secretion was obviously detected in MSCs transfected with Pdx1 cDNA by insulin release assay and the islet-like structure formed in Pdx1-expressing MSCs was stained into black-red by dithizone, while the native MSCs were opposite. |
| 3636 | 20306305 | In addition, we uncovered the close relationships among the expression of Pdx1, insulin and Ngn3 genes, whose expression indicated parallel changes after high glucose challenge, and the fluctuation of Pdx1 and Ngn3 partly resulted in the unstable release of insulin. |
| 3637 | 20306305 | Taken together, these findings demonstrated that the effective role of Pdx1 gene in inducing insulin-producing cells, which may shuttle to the nucleoplasm of MSCs under high glucose, then initiate the expression of native transcription factors Ngn3 and recruit other proteins, resulting in transactivation of the relevant genes including insulin and generation of β cell phenotype. |
| 3638 | 20306305 | Expression of Pdx1 mediates differentiation from mesenchymal stem cells into insulin-producing cells. |
| 3639 | 20306305 | Pancreatic duodenal homeobox 1 (Pdx1) plays a key role in the differentiation of various non-β-cells into insulin-producing cells, but the potential mechanism remains to be clarified. |
| 3640 | 20306305 | The purpose of this study was to confirm that the expression of Pdx1 could mediate the differentiation of rat mesenchymal stem cells (MSCs) into insulin-producing cells and evaluate the potential molecular mechanisms in the process that Pdx1 activates transcription of insulin gene. |
| 3641 | 20306305 | In this study, glucose-stimulated insulin secretion was obviously detected in MSCs transfected with Pdx1 cDNA by insulin release assay and the islet-like structure formed in Pdx1-expressing MSCs was stained into black-red by dithizone, while the native MSCs were opposite. |
| 3642 | 20306305 | In addition, we uncovered the close relationships among the expression of Pdx1, insulin and Ngn3 genes, whose expression indicated parallel changes after high glucose challenge, and the fluctuation of Pdx1 and Ngn3 partly resulted in the unstable release of insulin. |
| 3643 | 20306305 | Taken together, these findings demonstrated that the effective role of Pdx1 gene in inducing insulin-producing cells, which may shuttle to the nucleoplasm of MSCs under high glucose, then initiate the expression of native transcription factors Ngn3 and recruit other proteins, resulting in transactivation of the relevant genes including insulin and generation of β cell phenotype. |
| 3644 | 20306305 | Expression of Pdx1 mediates differentiation from mesenchymal stem cells into insulin-producing cells. |
| 3645 | 20306305 | Pancreatic duodenal homeobox 1 (Pdx1) plays a key role in the differentiation of various non-β-cells into insulin-producing cells, but the potential mechanism remains to be clarified. |
| 3646 | 20306305 | The purpose of this study was to confirm that the expression of Pdx1 could mediate the differentiation of rat mesenchymal stem cells (MSCs) into insulin-producing cells and evaluate the potential molecular mechanisms in the process that Pdx1 activates transcription of insulin gene. |
| 3647 | 20306305 | In this study, glucose-stimulated insulin secretion was obviously detected in MSCs transfected with Pdx1 cDNA by insulin release assay and the islet-like structure formed in Pdx1-expressing MSCs was stained into black-red by dithizone, while the native MSCs were opposite. |
| 3648 | 20306305 | In addition, we uncovered the close relationships among the expression of Pdx1, insulin and Ngn3 genes, whose expression indicated parallel changes after high glucose challenge, and the fluctuation of Pdx1 and Ngn3 partly resulted in the unstable release of insulin. |
| 3649 | 20306305 | Taken together, these findings demonstrated that the effective role of Pdx1 gene in inducing insulin-producing cells, which may shuttle to the nucleoplasm of MSCs under high glucose, then initiate the expression of native transcription factors Ngn3 and recruit other proteins, resulting in transactivation of the relevant genes including insulin and generation of β cell phenotype. |
| 3650 | 20354156 | LKB1 deletion with the RIP2.Cre transgene modifies pancreatic beta-cell morphology and enhances insulin secretion in vivo. |
| 3651 | 20354156 | LKB1 phosphorylates AMP-activated protein kinase (AMPK) and several related protein kinases. |
| 3652 | 20354156 | Whereas deletion of both catalytic isoforms of AMPK from the pancreatic beta-cell and hypothalamic neurons using the rat insulin promoter (RIP2).Cre transgene (betaAMPKdKO) diminishes insulin secretion in vivo, deletion of LKB1 in the beta-cell with an inducible Pdx-1.CreER transgene enhances insulin secretion in mice. |
| 3653 | 20354156 | In contrast to Pdx1-CreER-mediated deletion, the expression of Glut2, glucose-induced changes in membrane potential and intracellular Ca(2+) were sharply reduced in betaLKB1KO mouse islets and the stimulation of insulin secretion was modestly inhibited. |
| 3654 | 20354156 | We conclude that LKB1 and AMPK play distinct roles in the control of insulin secretion and that the timing of LKB1 deletion, and/or its loss from extrapancreatic sites, influences the final impact on beta-cell function. |
| 3655 | 20354156 | LKB1 deletion with the RIP2.Cre transgene modifies pancreatic beta-cell morphology and enhances insulin secretion in vivo. |
| 3656 | 20354156 | LKB1 phosphorylates AMP-activated protein kinase (AMPK) and several related protein kinases. |
| 3657 | 20354156 | Whereas deletion of both catalytic isoforms of AMPK from the pancreatic beta-cell and hypothalamic neurons using the rat insulin promoter (RIP2).Cre transgene (betaAMPKdKO) diminishes insulin secretion in vivo, deletion of LKB1 in the beta-cell with an inducible Pdx-1.CreER transgene enhances insulin secretion in mice. |
| 3658 | 20354156 | In contrast to Pdx1-CreER-mediated deletion, the expression of Glut2, glucose-induced changes in membrane potential and intracellular Ca(2+) were sharply reduced in betaLKB1KO mouse islets and the stimulation of insulin secretion was modestly inhibited. |
| 3659 | 20354156 | We conclude that LKB1 and AMPK play distinct roles in the control of insulin secretion and that the timing of LKB1 deletion, and/or its loss from extrapancreatic sites, influences the final impact on beta-cell function. |
| 3660 | 20382773 | On day 70, plasma glucose levels, plasma and pancreatic insulin levels, pancreatic islet area and number, insulin and pancreatic/duodenal homeobox-1 (Pdx1) gene expression, and antiapoptotic BCL2 protein expression were determined. |
| 3661 | 20382773 | Finally, in STZ-treated animals, UAG and Ob up-regulated insulin and Pdx1 mRNA and increased the expression of BCL2 similarly to AG. |
| 3662 | 20382773 | On day 70, plasma glucose levels, plasma and pancreatic insulin levels, pancreatic islet area and number, insulin and pancreatic/duodenal homeobox-1 (Pdx1) gene expression, and antiapoptotic BCL2 protein expression were determined. |
| 3663 | 20382773 | Finally, in STZ-treated animals, UAG and Ob up-regulated insulin and Pdx1 mRNA and increased the expression of BCL2 similarly to AG. |
| 3664 | 20424162 | Regulation of CCAAT/enhancer-binding protein homologous protein (CHOP) expression by interleukin-1 beta in pancreatic beta cells. |
| 3665 | 20424162 | Here, we show that nuclear factor kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK) signaling pathways regulate the expression of CCAAT/enhancer-binding protein homologous protein (CHOP), which mediates endoplasmic reticulum stress-induced apoptosis. |
| 3666 | 20424162 | Both CHOP mRNA and protein increase in beta cells treated with IL-1beta. |
| 3667 | 20424162 | IL-1beta also causes increased expression of C/EBP-beta and a reduction of MafA, NFATc2, and Pdx-1 expression in beta cells. |
| 3668 | 20424162 | Inhibition of the NF-kappaB and MAPK signaling pathways differentially attenuates CHOP expression. |
| 3669 | 20432450 | Neurogenin-3 and Pdx-1, markers of beta-cell progenitors, were increased in EIC of weanling HC-fed rats. |
| 3670 | 20448145 | Glial cell line-derived neurotrophic factor enhances neurogenin3 gene expression and beta-cell proliferation in the developing mouse pancreas. |
| 3671 | 20448145 | In this study we examined the influence of GDNF on the expression of neurogenin3 (Ngn3) and other transcription factors implicated in early beta-cell development, as well as on beta-cell proliferation during embryonic and early postnatal mouse pancreas development. |
| 3672 | 20448145 | Embryonic day 15.5 (E15.5) mouse pancreatic tissue when exposed to GDNF for 24 h showed higher Ngn3, pancreatic and duodenal homeobox gene 1 (Pdx1), neuroD1/beta(2), paired homeobox gene 4 (Pax4), and insulin mRNA expression than tissue exposed to vehicle only. |
| 3673 | 20448145 | Transgenic expression of GDNF in mouse pancreata was associated with increased numbers of Ngn3-expressing pancreatic cells and higher beta-cell mass at embryonic day 18 (E18), as well as higher beta-cell proliferation and Pdx1 expression in beta-cells at E18 and postnatal day 1. |
| 3674 | 20448145 | In the HIT-T15 beta-cell line, GDNF enhanced the expression of Pax6. |
| 3675 | 20448145 | Chromatin immunoprecipitation studies using the HIT-T15 beta-cell line demonstrated that GDNF can influence Pdx1 gene expression by enhancing the binding of Sox9 and neuroD1/beta(2) to the Pdx1 promoter. |
| 3676 | 20448145 | Glial cell line-derived neurotrophic factor enhances neurogenin3 gene expression and beta-cell proliferation in the developing mouse pancreas. |
| 3677 | 20448145 | In this study we examined the influence of GDNF on the expression of neurogenin3 (Ngn3) and other transcription factors implicated in early beta-cell development, as well as on beta-cell proliferation during embryonic and early postnatal mouse pancreas development. |
| 3678 | 20448145 | Embryonic day 15.5 (E15.5) mouse pancreatic tissue when exposed to GDNF for 24 h showed higher Ngn3, pancreatic and duodenal homeobox gene 1 (Pdx1), neuroD1/beta(2), paired homeobox gene 4 (Pax4), and insulin mRNA expression than tissue exposed to vehicle only. |
| 3679 | 20448145 | Transgenic expression of GDNF in mouse pancreata was associated with increased numbers of Ngn3-expressing pancreatic cells and higher beta-cell mass at embryonic day 18 (E18), as well as higher beta-cell proliferation and Pdx1 expression in beta-cells at E18 and postnatal day 1. |
| 3680 | 20448145 | In the HIT-T15 beta-cell line, GDNF enhanced the expression of Pax6. |
| 3681 | 20448145 | Chromatin immunoprecipitation studies using the HIT-T15 beta-cell line demonstrated that GDNF can influence Pdx1 gene expression by enhancing the binding of Sox9 and neuroD1/beta(2) to the Pdx1 promoter. |
| 3682 | 20448145 | Glial cell line-derived neurotrophic factor enhances neurogenin3 gene expression and beta-cell proliferation in the developing mouse pancreas. |
| 3683 | 20448145 | In this study we examined the influence of GDNF on the expression of neurogenin3 (Ngn3) and other transcription factors implicated in early beta-cell development, as well as on beta-cell proliferation during embryonic and early postnatal mouse pancreas development. |
| 3684 | 20448145 | Embryonic day 15.5 (E15.5) mouse pancreatic tissue when exposed to GDNF for 24 h showed higher Ngn3, pancreatic and duodenal homeobox gene 1 (Pdx1), neuroD1/beta(2), paired homeobox gene 4 (Pax4), and insulin mRNA expression than tissue exposed to vehicle only. |
| 3685 | 20448145 | Transgenic expression of GDNF in mouse pancreata was associated with increased numbers of Ngn3-expressing pancreatic cells and higher beta-cell mass at embryonic day 18 (E18), as well as higher beta-cell proliferation and Pdx1 expression in beta-cells at E18 and postnatal day 1. |
| 3686 | 20448145 | In the HIT-T15 beta-cell line, GDNF enhanced the expression of Pax6. |
| 3687 | 20448145 | Chromatin immunoprecipitation studies using the HIT-T15 beta-cell line demonstrated that GDNF can influence Pdx1 gene expression by enhancing the binding of Sox9 and neuroD1/beta(2) to the Pdx1 promoter. |
| 3688 | 20479245 | Targeting cyclophilin D and the mitochondrial permeability transition enhances beta-cell survival and prevents diabetes in Pdx1 deficiency. |
| 3689 | 20479245 | Genetic ablation of the Ppif gene, encoding cyclophilin D, restored beta-cell mass and decreased TUNEL and complement complex labeling without affecting beta-cell proliferation. |
| 3690 | 20479245 | In adult mice maintained on a high-fat diet, Ppif ablation normalized fasting glucose and glucose and insulin responses to acute glucose challenge. |
| 3691 | 20479245 | Thus, cyclophilin D and the mitochondrial permeability transition are critical regulators of beta-cell death caused by Pdx1 insufficiency. |
| 3692 | 20479245 | Targeting cyclophilin D and the mitochondrial permeability transition enhances beta-cell survival and prevents diabetes in Pdx1 deficiency. |
| 3693 | 20479245 | Genetic ablation of the Ppif gene, encoding cyclophilin D, restored beta-cell mass and decreased TUNEL and complement complex labeling without affecting beta-cell proliferation. |
| 3694 | 20479245 | In adult mice maintained on a high-fat diet, Ppif ablation normalized fasting glucose and glucose and insulin responses to acute glucose challenge. |
| 3695 | 20479245 | Thus, cyclophilin D and the mitochondrial permeability transition are critical regulators of beta-cell death caused by Pdx1 insufficiency. |
| 3696 | 20530463 | When cultivated in tissue culture-treated flasks, spheroid cells exhibited a proliferative capacity and coexpressed epithelial (cytokeratin7 and cytokeratin19) and mesenchymal (vimentin and alpha-smooth muscle actin) markers as well as marker of progenitor pancreatic cells (pancreatic duodenal homeobox factor-1) and surface markers of mesenchymal stem cells. |
| 3697 | 20586612 | Knockouts of SOD1 and GPX1 exert different impacts on murine islet function and pancreatic integrity. |
| 3698 | 20586612 | Using single knockout of Cu,Zn-superoxide dismutase (SOD1(-/-)) or Se-glutathione peroxidase-1 (GPX1(-/-)) and their double-knockout (DKO) mouse models, we determined if elevating endogenously-derived superoxide and hydroperoxide exerted distinct impacts and mechanisms on body glucose homeostasis. |
| 3699 | 20586612 | Whereas the three knockout groups displayed decreased plasma insulin concentrations and islet β-cells mass, only SOD1(-/-) showed decreased body weight, increased blood glucose, and blocked glucose-stimulated insulin secretion. |
| 3700 | 20586612 | Null of SOD1 and GPX1 elevated respective islet superoxide and hydroperoxide production, and upregulated p53 phosphorylation. |
| 3701 | 20586612 | Knockout of SOD1 downregulated the foxhead box A2/pancreatic and duodenal homeobox 1 pathway in a superoxide-dependent fashion at epigenetic, mRNA, and protein levels in islets, but improved insulin signaling in liver and muscle. |
| 3702 | 20586612 | The SOD1(-/-) mice showed more apparent pancreatitis than the GPX1(-/-) mice that were more susceptible to the cerulein-induced amylase increase. |
| 3703 | 20586612 | Knockout of SOD1 impaired islet function, pancreas integrity, and body glucose homeostasis more than that of GPX1. |
| 3704 | 20589757 | SREBP-1c, Pdx-1, and GLP-1R involved in palmitate-EPA regulated glucose-stimulated insulin secretion in INS-1 cells. |
| 3705 | 20589757 | Furthermore, palmitate was found to up-regulate the expression level of sterol regulatory element-binding protein (SREBP)-1c and down-regulate the levels of pancreatic and duodenal homeobox (Pdx)-1 and glucagon-like peptide (GLP)-1 receptor (GLP-1R) in INS-1 cells. |
| 3706 | 20589757 | It was found that palmitate failed to suppress the expression of Pdx-1 and GLP-1R in SREBP-1c-deficient INS-1 cells. |
| 3707 | 20589757 | Moreover, down-regulation of Pdx-1 could cause the low expression of GLP-1R with/without palmitate treatment. |
| 3708 | 20589757 | SREBP-1c, Pdx-1, and GLP-1R involved in palmitate-EPA regulated glucose-stimulated insulin secretion in INS-1 cells. |
| 3709 | 20589757 | Furthermore, palmitate was found to up-regulate the expression level of sterol regulatory element-binding protein (SREBP)-1c and down-regulate the levels of pancreatic and duodenal homeobox (Pdx)-1 and glucagon-like peptide (GLP)-1 receptor (GLP-1R) in INS-1 cells. |
| 3710 | 20589757 | It was found that palmitate failed to suppress the expression of Pdx-1 and GLP-1R in SREBP-1c-deficient INS-1 cells. |
| 3711 | 20589757 | Moreover, down-regulation of Pdx-1 could cause the low expression of GLP-1R with/without palmitate treatment. |
| 3712 | 20589757 | SREBP-1c, Pdx-1, and GLP-1R involved in palmitate-EPA regulated glucose-stimulated insulin secretion in INS-1 cells. |
| 3713 | 20589757 | Furthermore, palmitate was found to up-regulate the expression level of sterol regulatory element-binding protein (SREBP)-1c and down-regulate the levels of pancreatic and duodenal homeobox (Pdx)-1 and glucagon-like peptide (GLP)-1 receptor (GLP-1R) in INS-1 cells. |
| 3714 | 20589757 | It was found that palmitate failed to suppress the expression of Pdx-1 and GLP-1R in SREBP-1c-deficient INS-1 cells. |
| 3715 | 20589757 | Moreover, down-regulation of Pdx-1 could cause the low expression of GLP-1R with/without palmitate treatment. |
| 3716 | 20589757 | SREBP-1c, Pdx-1, and GLP-1R involved in palmitate-EPA regulated glucose-stimulated insulin secretion in INS-1 cells. |
| 3717 | 20589757 | Furthermore, palmitate was found to up-regulate the expression level of sterol regulatory element-binding protein (SREBP)-1c and down-regulate the levels of pancreatic and duodenal homeobox (Pdx)-1 and glucagon-like peptide (GLP)-1 receptor (GLP-1R) in INS-1 cells. |
| 3718 | 20589757 | It was found that palmitate failed to suppress the expression of Pdx-1 and GLP-1R in SREBP-1c-deficient INS-1 cells. |
| 3719 | 20589757 | Moreover, down-regulation of Pdx-1 could cause the low expression of GLP-1R with/without palmitate treatment. |
| 3720 | 20663919 | In young foci, ductules express markers of the embryonic pancreatic epithelium - Pdx1, Tcf2 and Sox9 - suggesting that these cells act as progenitors of the regenerating pancreas. |
| 3721 | 20692412 | Compared with untreated cells the differentiation of human nonendocrine pancreatic cells into insulin-producing elements was increased after treatment with IGF-1, EGF, and Exendin-4, growth factors known to be activators of the PI3K pathway (12.2 +/- 3.2% vs 9.1 +/- 3.2%). |
| 3722 | 20692412 | Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed that insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), and Exendin-4 significantly increased the expression of the transcription factor neurogenin-3, whereas the expressions of pancreatic and duodenal homeobox 1 (PDX-1), neurogenic differentiation 1 (NeuroD) were increased only among samples treated with ZnCl2 and not significantly affected by treatment with the tested growth factors. |
| 3723 | 20692412 | Successful differentiation of IGF-1, EGF-, and Exendin-4-treated cells into functional beta cells was confirmed by C-peptide secretion in response to 5 versus 20 mmol glucose stimulation (0.24 vs 0.91 pmol C-peptide/microg DNA). |
| 3724 | 20692412 | These results showed that activation of the PI3K signaling pathway might be used to stimulate the differentiation of nonendocrine pancreatic cells into insulin-producing elements. |
| 3725 | 20717889 | More than 70% of differentiated cells positively upregulated Pdx-1, along with pro-endocrine transcription factors Ngn3, β2/neroD1, Nkx2.2 and Nkx6.1. |
| 3726 | 20717889 | Final maturation to islet-specific cells is achieved by co-culturing the ESC-derived pancreatic endocrine cells with endothelial cells, which resulted in Insulin 1 upregulation in 60% of the cell population, along with high levels of IAPP and Glut2. |
| 3727 | 20811152 | Pcif1 modulates Pdx1 protein stability and pancreatic β cell function and survival in mice. |
| 3728 | 20811152 | The homeodomain transcription factor pancreatic duodenal homeobox 1 (Pdx1) is a major mediator of insulin transcription and a key regulator of the β cell phenotype. |
| 3729 | 20811152 | Pdx1 C terminus-interacting factor-1 (Pcif1, also known as SPOP) is a nuclear protein that inhibits Pdx1 transactivation. |
| 3730 | 20811152 | Here, we show that Pcif1 targets Pdx1 for ubiquitination and proteasomal degradation. |
| 3731 | 20811152 | Silencing of Pcif1 increased Pdx1 protein levels in cultured mouse β cells, and Pcif1 heterozygosity normalized Pdx1 protein levels in Pdx1(+/-) mouse islets, thereby increasing expression of key Pdx1 transcriptional targets. |
| 3732 | 20811152 | Remarkably, Pcif1 heterozygosity improved glucose homeostasis and β cell function and normalized β cell mass in Pdx1(+/-) mice by modulating β cell survival. |
| 3733 | 20811152 | These findings indicate that in adult mouse β cells, Pcif1 limits Pdx1 protein accumulation and thus the expression of insulin and other gene targets important in the maintenance of β cell mass and function. |
| 3734 | 20811152 | Pcif1 modulates Pdx1 protein stability and pancreatic β cell function and survival in mice. |
| 3735 | 20811152 | The homeodomain transcription factor pancreatic duodenal homeobox 1 (Pdx1) is a major mediator of insulin transcription and a key regulator of the β cell phenotype. |
| 3736 | 20811152 | Pdx1 C terminus-interacting factor-1 (Pcif1, also known as SPOP) is a nuclear protein that inhibits Pdx1 transactivation. |
| 3737 | 20811152 | Here, we show that Pcif1 targets Pdx1 for ubiquitination and proteasomal degradation. |
| 3738 | 20811152 | Silencing of Pcif1 increased Pdx1 protein levels in cultured mouse β cells, and Pcif1 heterozygosity normalized Pdx1 protein levels in Pdx1(+/-) mouse islets, thereby increasing expression of key Pdx1 transcriptional targets. |
| 3739 | 20811152 | Remarkably, Pcif1 heterozygosity improved glucose homeostasis and β cell function and normalized β cell mass in Pdx1(+/-) mice by modulating β cell survival. |
| 3740 | 20811152 | These findings indicate that in adult mouse β cells, Pcif1 limits Pdx1 protein accumulation and thus the expression of insulin and other gene targets important in the maintenance of β cell mass and function. |
| 3741 | 20811152 | Pcif1 modulates Pdx1 protein stability and pancreatic β cell function and survival in mice. |
| 3742 | 20811152 | The homeodomain transcription factor pancreatic duodenal homeobox 1 (Pdx1) is a major mediator of insulin transcription and a key regulator of the β cell phenotype. |
| 3743 | 20811152 | Pdx1 C terminus-interacting factor-1 (Pcif1, also known as SPOP) is a nuclear protein that inhibits Pdx1 transactivation. |
| 3744 | 20811152 | Here, we show that Pcif1 targets Pdx1 for ubiquitination and proteasomal degradation. |
| 3745 | 20811152 | Silencing of Pcif1 increased Pdx1 protein levels in cultured mouse β cells, and Pcif1 heterozygosity normalized Pdx1 protein levels in Pdx1(+/-) mouse islets, thereby increasing expression of key Pdx1 transcriptional targets. |
| 3746 | 20811152 | Remarkably, Pcif1 heterozygosity improved glucose homeostasis and β cell function and normalized β cell mass in Pdx1(+/-) mice by modulating β cell survival. |
| 3747 | 20811152 | These findings indicate that in adult mouse β cells, Pcif1 limits Pdx1 protein accumulation and thus the expression of insulin and other gene targets important in the maintenance of β cell mass and function. |
| 3748 | 20811152 | Pcif1 modulates Pdx1 protein stability and pancreatic β cell function and survival in mice. |
| 3749 | 20811152 | The homeodomain transcription factor pancreatic duodenal homeobox 1 (Pdx1) is a major mediator of insulin transcription and a key regulator of the β cell phenotype. |
| 3750 | 20811152 | Pdx1 C terminus-interacting factor-1 (Pcif1, also known as SPOP) is a nuclear protein that inhibits Pdx1 transactivation. |
| 3751 | 20811152 | Here, we show that Pcif1 targets Pdx1 for ubiquitination and proteasomal degradation. |
| 3752 | 20811152 | Silencing of Pcif1 increased Pdx1 protein levels in cultured mouse β cells, and Pcif1 heterozygosity normalized Pdx1 protein levels in Pdx1(+/-) mouse islets, thereby increasing expression of key Pdx1 transcriptional targets. |
| 3753 | 20811152 | Remarkably, Pcif1 heterozygosity improved glucose homeostasis and β cell function and normalized β cell mass in Pdx1(+/-) mice by modulating β cell survival. |
| 3754 | 20811152 | These findings indicate that in adult mouse β cells, Pcif1 limits Pdx1 protein accumulation and thus the expression of insulin and other gene targets important in the maintenance of β cell mass and function. |
| 3755 | 20811152 | Pcif1 modulates Pdx1 protein stability and pancreatic β cell function and survival in mice. |
| 3756 | 20811152 | The homeodomain transcription factor pancreatic duodenal homeobox 1 (Pdx1) is a major mediator of insulin transcription and a key regulator of the β cell phenotype. |
| 3757 | 20811152 | Pdx1 C terminus-interacting factor-1 (Pcif1, also known as SPOP) is a nuclear protein that inhibits Pdx1 transactivation. |
| 3758 | 20811152 | Here, we show that Pcif1 targets Pdx1 for ubiquitination and proteasomal degradation. |
| 3759 | 20811152 | Silencing of Pcif1 increased Pdx1 protein levels in cultured mouse β cells, and Pcif1 heterozygosity normalized Pdx1 protein levels in Pdx1(+/-) mouse islets, thereby increasing expression of key Pdx1 transcriptional targets. |
| 3760 | 20811152 | Remarkably, Pcif1 heterozygosity improved glucose homeostasis and β cell function and normalized β cell mass in Pdx1(+/-) mice by modulating β cell survival. |
| 3761 | 20811152 | These findings indicate that in adult mouse β cells, Pcif1 limits Pdx1 protein accumulation and thus the expression of insulin and other gene targets important in the maintenance of β cell mass and function. |
| 3762 | 20811152 | Pcif1 modulates Pdx1 protein stability and pancreatic β cell function and survival in mice. |
| 3763 | 20811152 | The homeodomain transcription factor pancreatic duodenal homeobox 1 (Pdx1) is a major mediator of insulin transcription and a key regulator of the β cell phenotype. |
| 3764 | 20811152 | Pdx1 C terminus-interacting factor-1 (Pcif1, also known as SPOP) is a nuclear protein that inhibits Pdx1 transactivation. |
| 3765 | 20811152 | Here, we show that Pcif1 targets Pdx1 for ubiquitination and proteasomal degradation. |
| 3766 | 20811152 | Silencing of Pcif1 increased Pdx1 protein levels in cultured mouse β cells, and Pcif1 heterozygosity normalized Pdx1 protein levels in Pdx1(+/-) mouse islets, thereby increasing expression of key Pdx1 transcriptional targets. |
| 3767 | 20811152 | Remarkably, Pcif1 heterozygosity improved glucose homeostasis and β cell function and normalized β cell mass in Pdx1(+/-) mice by modulating β cell survival. |
| 3768 | 20811152 | These findings indicate that in adult mouse β cells, Pcif1 limits Pdx1 protein accumulation and thus the expression of insulin and other gene targets important in the maintenance of β cell mass and function. |
| 3769 | 20811152 | Pcif1 modulates Pdx1 protein stability and pancreatic β cell function and survival in mice. |
| 3770 | 20811152 | The homeodomain transcription factor pancreatic duodenal homeobox 1 (Pdx1) is a major mediator of insulin transcription and a key regulator of the β cell phenotype. |
| 3771 | 20811152 | Pdx1 C terminus-interacting factor-1 (Pcif1, also known as SPOP) is a nuclear protein that inhibits Pdx1 transactivation. |
| 3772 | 20811152 | Here, we show that Pcif1 targets Pdx1 for ubiquitination and proteasomal degradation. |
| 3773 | 20811152 | Silencing of Pcif1 increased Pdx1 protein levels in cultured mouse β cells, and Pcif1 heterozygosity normalized Pdx1 protein levels in Pdx1(+/-) mouse islets, thereby increasing expression of key Pdx1 transcriptional targets. |
| 3774 | 20811152 | Remarkably, Pcif1 heterozygosity improved glucose homeostasis and β cell function and normalized β cell mass in Pdx1(+/-) mice by modulating β cell survival. |
| 3775 | 20811152 | These findings indicate that in adult mouse β cells, Pcif1 limits Pdx1 protein accumulation and thus the expression of insulin and other gene targets important in the maintenance of β cell mass and function. |
| 3776 | 20816753 | G-protein-coupled receptor (GPR) 119 is involved in glucose-stimulated insulin secretion (GSIS) and represents a promising target for the treatment of type 2 diabetes as it is highly expressed in pancreatic β-cells. |
| 3777 | 20816753 | The exposure of HEK293 cells expressing human GPR119, NIT-1 cells expressing human insulin promoter, and the pancreatic β-cell line MIN-6-B1 to AS1907417, enhanced intracellular cAMP, GSIS, and human insulin promoter activity, respectively. |
| 3778 | 20816753 | In db/db mice, AS1907417 improved plasma glucose, plasma insulin, pancreatic insulin content, lipid profiles, and increased pancreatic insulin and pancreatic and duodenal homeobox 1 (PDX-1) mRNA levels. |
| 3779 | 20886041 | A multi-parameter, high-content, high-throughput screening platform to identify natural compounds that modulate insulin and Pdx1 expression. |
| 3780 | 20886041 | Dispersed human pancreatic islets and MIN6 beta-cells were infected with a dual reporter lentivirus containing both eGFP driven by the insulin promoter and mRFP driven by the pdx1 promoter. |
| 3781 | 20886041 | Using this approach and 5 replicate screens, we identified 7 extracts that reproducibly changed insulin and/or pdx1 promoter activity from a library of 1319 marine invertebrate extracts. |
| 3782 | 20886041 | A multi-parameter, high-content, high-throughput screening platform to identify natural compounds that modulate insulin and Pdx1 expression. |
| 3783 | 20886041 | Dispersed human pancreatic islets and MIN6 beta-cells were infected with a dual reporter lentivirus containing both eGFP driven by the insulin promoter and mRFP driven by the pdx1 promoter. |
| 3784 | 20886041 | Using this approach and 5 replicate screens, we identified 7 extracts that reproducibly changed insulin and/or pdx1 promoter activity from a library of 1319 marine invertebrate extracts. |
| 3785 | 20886041 | A multi-parameter, high-content, high-throughput screening platform to identify natural compounds that modulate insulin and Pdx1 expression. |
| 3786 | 20886041 | Dispersed human pancreatic islets and MIN6 beta-cells were infected with a dual reporter lentivirus containing both eGFP driven by the insulin promoter and mRFP driven by the pdx1 promoter. |
| 3787 | 20886041 | Using this approach and 5 replicate screens, we identified 7 extracts that reproducibly changed insulin and/or pdx1 promoter activity from a library of 1319 marine invertebrate extracts. |
| 3788 | 20934404 | ChREBP regulates Pdx-1 and other glucose-sensitive genes in pancreatic β-cells. |
| 3789 | 20934404 | We show here that ChREBP inactivation in clonal pancreatic MIN6 β-cells results in an increase in Pdx-1 expression at low glucose and to a small, but significant, increase in Ins2, GcK and MafA gene expression at high glucose concentrations. |
| 3790 | 20934404 | Conversely, adenovirus-mediated over-expression of ChREBP in mouse pancreatic islets results in decreases in Pdx-1, MafA, Ins1, Ins2 and GcK mRNA levels. |
| 3791 | 20934404 | ChREBP regulates Pdx-1 and other glucose-sensitive genes in pancreatic β-cells. |
| 3792 | 20934404 | We show here that ChREBP inactivation in clonal pancreatic MIN6 β-cells results in an increase in Pdx-1 expression at low glucose and to a small, but significant, increase in Ins2, GcK and MafA gene expression at high glucose concentrations. |
| 3793 | 20934404 | Conversely, adenovirus-mediated over-expression of ChREBP in mouse pancreatic islets results in decreases in Pdx-1, MafA, Ins1, Ins2 and GcK mRNA levels. |
| 3794 | 20934404 | ChREBP regulates Pdx-1 and other glucose-sensitive genes in pancreatic β-cells. |
| 3795 | 20934404 | We show here that ChREBP inactivation in clonal pancreatic MIN6 β-cells results in an increase in Pdx-1 expression at low glucose and to a small, but significant, increase in Ins2, GcK and MafA gene expression at high glucose concentrations. |
| 3796 | 20934404 | Conversely, adenovirus-mediated over-expression of ChREBP in mouse pancreatic islets results in decreases in Pdx-1, MafA, Ins1, Ins2 and GcK mRNA levels. |
| 3797 | 21082287 | At the fifth passages, MSCs were confirmed by flow cytometry about expression of CD13, CD14, CD34, CD45, CD166, and HLA-DR markers; after that, they were induced to differentiate into adipocytes and osteoblasts. |
| 3798 | 21082287 | Using real-time reverse transcription polymerase chain reaction (RT-PCR) to analyze the expression of functional genes, the result showed that Nestin, Pdx-1, Ngn3, Ils-1, Pax6, Pax4, Nkx2.2, Nkx6.1, Glut-2, Insulin genes expressed. |
| 3799 | 21099272 | We successfully cloned the Acomys Pdx-1 gene and we demonstrate by immunocytochemistry that the Pdx-1 protein is expressed in the pancreatic insulin immunoreactive cells and in a subset of the somatostatin cells. |
| 3800 | 21099272 | The basic islet structure is very similar to other rodents - with the insulin cells in the center, and glucagon, somatostatin, PP and occasional PYY cells in the periphery. |
| 3801 | 21099272 | Nkx6.1 was localized specifically to the insulin immunoreactive cells, while Nkx2.2 was found in all endocrine cells except the somatostatin immunoreactive cells. |
| 3802 | 21099272 | Both MafA and MafB were expressed in the islets; MafA being specific for the insulin cells, while MafB was primarily in the glucagon cells but also found in some insulin cells. |
| 3803 | 21099283 | We had suggested that the methylation of H3-Lys4 by Set7/9 enhances accessibility of the insulin gene to the basal transcriptional machinery. |
| 3804 | 21099283 | Consistent with this hypothesis, we show here that RNA polymerase II occupancy at the insulin and IAPP genes is considerably enhanced in β-cells compared to α cells (or NIH3T3 cells), and that the converse is true for RNA polymerase II occupancy at the glucagon gene. |
| 3805 | 21099283 | The enrichment of Set7/9 in β-cells appears to be dependent upon Pdx1, as knockdown of Pdx1 in INS-1 β-cells using small hairpin RNAs almost completely abolishes Set7/9 expression. |
| 3806 | 21099283 | A LacZ expression vector driven by the -6.5 kilobase pair Set7/9 promoter that contains putative Pdx1 binding sites shows β-cell-line-specific expression. |
| 3807 | 21099283 | Taken together, our data support further the hypothesis that Pdx1-dependent Set7/9 expression may be crucial to enhancing chromatin accessibility and transcription of β-cell genes. |
| 3808 | 21099283 | We had suggested that the methylation of H3-Lys4 by Set7/9 enhances accessibility of the insulin gene to the basal transcriptional machinery. |
| 3809 | 21099283 | Consistent with this hypothesis, we show here that RNA polymerase II occupancy at the insulin and IAPP genes is considerably enhanced in β-cells compared to α cells (or NIH3T3 cells), and that the converse is true for RNA polymerase II occupancy at the glucagon gene. |
| 3810 | 21099283 | The enrichment of Set7/9 in β-cells appears to be dependent upon Pdx1, as knockdown of Pdx1 in INS-1 β-cells using small hairpin RNAs almost completely abolishes Set7/9 expression. |
| 3811 | 21099283 | A LacZ expression vector driven by the -6.5 kilobase pair Set7/9 promoter that contains putative Pdx1 binding sites shows β-cell-line-specific expression. |
| 3812 | 21099283 | Taken together, our data support further the hypothesis that Pdx1-dependent Set7/9 expression may be crucial to enhancing chromatin accessibility and transcription of β-cell genes. |
| 3813 | 21099283 | We had suggested that the methylation of H3-Lys4 by Set7/9 enhances accessibility of the insulin gene to the basal transcriptional machinery. |
| 3814 | 21099283 | Consistent with this hypothesis, we show here that RNA polymerase II occupancy at the insulin and IAPP genes is considerably enhanced in β-cells compared to α cells (or NIH3T3 cells), and that the converse is true for RNA polymerase II occupancy at the glucagon gene. |
| 3815 | 21099283 | The enrichment of Set7/9 in β-cells appears to be dependent upon Pdx1, as knockdown of Pdx1 in INS-1 β-cells using small hairpin RNAs almost completely abolishes Set7/9 expression. |
| 3816 | 21099283 | A LacZ expression vector driven by the -6.5 kilobase pair Set7/9 promoter that contains putative Pdx1 binding sites shows β-cell-line-specific expression. |
| 3817 | 21099283 | Taken together, our data support further the hypothesis that Pdx1-dependent Set7/9 expression may be crucial to enhancing chromatin accessibility and transcription of β-cell genes. |
| 3818 | 21099303 | Human umbilical cord matrix stem cells (hUCMSCs) were found to express CD29, CD44, CD73, CD90, CD105, smooth muscle actin, nestin, vimentin, proliferation marker Ki67 and embryonic markers Oct4, SSEA4. |
| 3819 | 21099303 | These were found to be negative for CD33, CD34, CD45 and HLA DR. |
| 3820 | 21099303 | Real time qPCR analysis of newly generated islets further demonstrated abundance of Pdx-1, Ngn3, insulin, glucagon and somatostatin transcripts. |
| 3821 | 21108535 | NKX6.1 promotes PDX-1-induced liver to pancreatic β-cells reprogramming. |
| 3822 | 21108535 | NKX6.1 is a transcription factor uniquely expressed in β-cells of the adult pancreas, its potential role in reprogramming liver cells to pancreatic lineages has never been analyzed. |
| 3823 | 21108535 | Our results suggest that NKX6.1 activates immature pancreatic markers such as NGN-3 and ISL-1 but not pancreatic hormones gene expression in human liver cells. |
| 3824 | 21108535 | Indeed, the complementation of NKX6.1 by ectopic PDX-1 expression substantially and specifically promoted insulin expression and glucose regulated processed hormone secretion to a higher extent than that of PDX-1 alone, without increasing the reprogrammed cells. |
| 3825 | 21108535 | This may suggest a potential role for NKX6.1 in promoting PDX-1 reprogrammed cells maturation along the β-cell-like lineage. |
| 3826 | 21108535 | By contrast, NKX6.1 repressed PDX-1 induced proglucagon gene expression. |
| 3827 | 21108535 | NKX6.1 promotes PDX-1-induced liver to pancreatic β-cells reprogramming. |
| 3828 | 21108535 | NKX6.1 is a transcription factor uniquely expressed in β-cells of the adult pancreas, its potential role in reprogramming liver cells to pancreatic lineages has never been analyzed. |
| 3829 | 21108535 | Our results suggest that NKX6.1 activates immature pancreatic markers such as NGN-3 and ISL-1 but not pancreatic hormones gene expression in human liver cells. |
| 3830 | 21108535 | Indeed, the complementation of NKX6.1 by ectopic PDX-1 expression substantially and specifically promoted insulin expression and glucose regulated processed hormone secretion to a higher extent than that of PDX-1 alone, without increasing the reprogrammed cells. |
| 3831 | 21108535 | This may suggest a potential role for NKX6.1 in promoting PDX-1 reprogrammed cells maturation along the β-cell-like lineage. |
| 3832 | 21108535 | By contrast, NKX6.1 repressed PDX-1 induced proglucagon gene expression. |
| 3833 | 21108535 | NKX6.1 promotes PDX-1-induced liver to pancreatic β-cells reprogramming. |
| 3834 | 21108535 | NKX6.1 is a transcription factor uniquely expressed in β-cells of the adult pancreas, its potential role in reprogramming liver cells to pancreatic lineages has never been analyzed. |
| 3835 | 21108535 | Our results suggest that NKX6.1 activates immature pancreatic markers such as NGN-3 and ISL-1 but not pancreatic hormones gene expression in human liver cells. |
| 3836 | 21108535 | Indeed, the complementation of NKX6.1 by ectopic PDX-1 expression substantially and specifically promoted insulin expression and glucose regulated processed hormone secretion to a higher extent than that of PDX-1 alone, without increasing the reprogrammed cells. |
| 3837 | 21108535 | This may suggest a potential role for NKX6.1 in promoting PDX-1 reprogrammed cells maturation along the β-cell-like lineage. |
| 3838 | 21108535 | By contrast, NKX6.1 repressed PDX-1 induced proglucagon gene expression. |
| 3839 | 21108535 | NKX6.1 promotes PDX-1-induced liver to pancreatic β-cells reprogramming. |
| 3840 | 21108535 | NKX6.1 is a transcription factor uniquely expressed in β-cells of the adult pancreas, its potential role in reprogramming liver cells to pancreatic lineages has never been analyzed. |
| 3841 | 21108535 | Our results suggest that NKX6.1 activates immature pancreatic markers such as NGN-3 and ISL-1 but not pancreatic hormones gene expression in human liver cells. |
| 3842 | 21108535 | Indeed, the complementation of NKX6.1 by ectopic PDX-1 expression substantially and specifically promoted insulin expression and glucose regulated processed hormone secretion to a higher extent than that of PDX-1 alone, without increasing the reprogrammed cells. |
| 3843 | 21108535 | This may suggest a potential role for NKX6.1 in promoting PDX-1 reprogrammed cells maturation along the β-cell-like lineage. |
| 3844 | 21108535 | By contrast, NKX6.1 repressed PDX-1 induced proglucagon gene expression. |
| 3845 | 21115832 | Here, we identify 9cRA in mouse pancreas by liquid chromatography/tandem mass spectrometry (LC/MS/MS), and show that 9cRA decreases with feeding and after glucose dosing and varies inversely with serum insulin. 9cRA reduces glucose-stimulated insulin secretion (GSIS) in mouse islets and in the rat β-cell line 832/13 within 15 min by reducing glucose transporter type 2 (Glut2) and glucokinase (GK) activities. 9cRA also reduces Pdx-1 and HNF4α mRNA expression, ∼8- and 80-fold, respectively: defects in Pdx-1 or HNF4α cause maturity onset diabetes of the young (MODY4 and 1, respectively), as does a defective GK gene (MODY2). |
| 3846 | 21149438 | The presence of the neural stem cell marker nestin, duct cell marker cytokeratin 19, and endocrine cell markers C-peptide and pancreatic and duodenal homeobox 1, was also observed. |
| 3847 | 21152387 | Differentiated cells displayed increased Sox17 and Foxa2 expression consistent with definitive endoderm production. |
| 3848 | 21152387 | Various assays revealed that the cell clusters generated by this protocol express markers of the pancreatic lineage including insulin I, insulin II, C-peptide, PDX-1, carboxypeptidase E, pan-cytokeratin, amylase, glucagon, PAX6, Ngn3 and Nkx6.1. |
| 3849 | 21177833 | Integrin {alpha}3, but not {beta}1, regulates islet cell survival and function via PI3K/Akt signaling pathways. |
| 3850 | 21177833 | Previously, we have shown that human fetal islet and INS-1 cells highly express α3β1-integrin and that collagens I and IV significantly enhance their survival and function; in addition, blocking β1 function in the fetal islet cells decreased adhesion on collagen I and increased apoptosis. |
| 3851 | 21177833 | Perturbing α3 function in human islet or INS-1 cells resulted in significant decreases in cell function (adhesion, spreading, proliferation and Pdx1 and insulin expression/secretion), primarily on collagen IV. |
| 3852 | 21177833 | A significant decrease in focal adhesion kinase and ERK1/2 phosphorylation and increased caspase3 cleavage were observed on both collagens. |
| 3853 | 21177833 | Interestingly, only α3 blockade reduced expression of phospho-Akt and members of its downstream signaling cascades (glycogen synthase kinase β and X-linked inhibitor of apoptosis), demonstrating a specific effect of α3 on the phosphatidylinositol 3-kinase/Akt pathway. |
| 3854 | 21197448 | This was a prospective open-labeled clinical trial to test efficacy and safety of IS-AD-MSC+CBM co-transplantation to treat IDDM, approved by the institutional review board after informed consent in 11 (males : females: 7 : 4) patients with 1-24-year disease duration, in age group: 13-43 years, on mean values of exogenous insulin requirement of 1.14 units/kg BW/day, glycosylated hemoglobin (Hb1Ac): 8.47%, and c-peptide levels: 0.1 ng/mL. |
| 3855 | 21197448 | Intraportal infusion of xenogeneic-free IS-AD-MSC from living donors, subjected to defined culture conditions and phenotypically differentiated to insulin-secreting cells, with mean quantum: 1.5 mL, expressing Pax-6, Isl-1, and pdx-1, cell counts: 2.1 × 10(3)/μL, CD45(-)/90(+)/73(+):40/30.1%, C-Peptide level:1.8 ng/mL, and insulin level: 339.3 IU/mL with CBM mean quantum: 96.3 mL and cell counts: 28.1 × 10(3)/μL, CD45(-)/34(+):0.62%, was carried out. |
| 3856 | 21209957 | NADPH oxidase 2-derived reactive oxygen species mediate FFAs-induced dysfunction and apoptosis of β-cells via JNK, p38 MAPK and p53 pathways. |
| 3857 | 21209957 | Our results show that palmitate and oleate (0.5 mmol/L, 48 h) induced JNK activation and AKT inhibition which resulted in decreased phosphorylation of FOXO1 following nuclear localization and the nucleocytoplasmic translocation of PDX-1, leading to the reducing of insulin and ultimately dysfunction of pancreatic NIT-1 cells. |
| 3858 | 21251764 | Milk signalling down-regulates the key transcription factor FoxO1 leading to up-regulation of insulin promoter factor-1 which stimulates β-cell proliferation, insulin secretion as well as coexpression of islet amyloid polypeptide (IAPP). |
| 3859 | 21285317 | Sexually dimorphic diet-induced insulin resistance in obese tissue inhibitor of metalloproteinase-2 (TIMP-2)-deficient mice. |
| 3860 | 21285317 | The effects of diet on glucose tolerance and insulin sensitivity, as well as pancreatic β-cell and adipocyte physiology, were assessed. |
| 3861 | 21285317 | Chow-fed TIMP-2 KO mice of both sexes became obese but maintained relatively normal glucose tolerance and insulin sensitivity. |
| 3862 | 21285317 | However, HFD-fed male, but not female, TIMP-2 KO mice developed insulin resistance with reduced glucose transporter 2 and pancreatic and duodenal homeobox 1 levels, despite increased β-cell mass and hyperplasia. |
| 3863 | 21285317 | Strikingly, MMP-14 expression increased to a greater extent in TIMP-2 KO males and was associated with decreased adipocyte collagen. |
| 3864 | 21285317 | Taken together, these findings demonstrate a role for TIMP-2 in maintaining extracellular matrix integrity necessary for normal β-cell and adipocyte physiology and that loss of extracellular matrix integrity may underlie diabetic and obesogenic phenotypes. |
| 3865 | 21308865 | CD24: a novel surface marker for PDX1-positive pancreatic progenitors derived from human embryonic stem cells. |
| 3866 | 21308865 | By costaining PDX1 and a panel of cell surface antigens at the pancreatic progenitor stage of human ESC differentiation, we discovered a positive marker, CD24. |
| 3867 | 21308865 | In addition, CD24-positive cells could differentiate into insulin-producing cells but CD24-negative cells could not. |
| 3868 | 21308865 | These results indicate that CD24 could be a surface marker for PDX1-positive pancreatic progenitors derived from human ESCs. |
| 3869 | 21308865 | CD24: a novel surface marker for PDX1-positive pancreatic progenitors derived from human embryonic stem cells. |
| 3870 | 21308865 | By costaining PDX1 and a panel of cell surface antigens at the pancreatic progenitor stage of human ESC differentiation, we discovered a positive marker, CD24. |
| 3871 | 21308865 | In addition, CD24-positive cells could differentiate into insulin-producing cells but CD24-negative cells could not. |
| 3872 | 21308865 | These results indicate that CD24 could be a surface marker for PDX1-positive pancreatic progenitors derived from human ESCs. |
| 3873 | 21308865 | CD24: a novel surface marker for PDX1-positive pancreatic progenitors derived from human embryonic stem cells. |
| 3874 | 21308865 | By costaining PDX1 and a panel of cell surface antigens at the pancreatic progenitor stage of human ESC differentiation, we discovered a positive marker, CD24. |
| 3875 | 21308865 | In addition, CD24-positive cells could differentiate into insulin-producing cells but CD24-negative cells could not. |
| 3876 | 21308865 | These results indicate that CD24 could be a surface marker for PDX1-positive pancreatic progenitors derived from human ESCs. |
| 3877 | 21333726 | Hybrid of 1-deoxynojirimycin and polysaccharide from mulberry leaves treat diabetes mellitus by activating PDX-1/insulin-1 signaling pathway and regulating the expression of glucokinase, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in alloxan-induced diabetic mice. |
| 3878 | 21335539 | The identity of ICAs was confirmed as islets by dithiozone-positive staining, as well as by expression of C-peptide, Pdx-1, Pax4, Pax6, Ngn3, and Isl-1. |
| 3879 | 21335550 | FoxO1 activity is tightly controlled by phosphatidylinositol 3-kinase (PI3K) signaling, resulting in its phosphorylation and nuclear exclusion. |
| 3880 | 21335550 | We sought here to determine the mechanisms involved in glucose and insulin-stimulated nuclear shuttling of FoxO1 in pancreatic β cells and its consequences for preproinsulin (Ins1, Ins2) gene expression. |
| 3881 | 21335550 | Constitutively active PI3K or protein kinase B/Akt exerted similar effects, while inhibitors of PI3K, but not of glycogen synthase kinase-3 or p70 S6 kinase, blocked nuclear export. |
| 3882 | 21335550 | FoxO1 overexpression reversed the activation by glucose of pancreatic duodenum homeobox-1 (Pdx1) transcription. |
| 3883 | 21335550 | A 915-bp glucose-responsive Ins2 promoter was inhibited by constitutively active FoxO1, an effect unaltered by simultaneous overexpression of PDX1. |
| 3884 | 21335550 | We conclude that nuclear import of FoxO1 contributes to the suppression of Pdx1 and Ins2 gene expression at low glucose, the latter via a previously unsuspected and direct physical interaction with the Ins2 promoter. |
| 3885 | 21335550 | FoxO1 activity is tightly controlled by phosphatidylinositol 3-kinase (PI3K) signaling, resulting in its phosphorylation and nuclear exclusion. |
| 3886 | 21335550 | We sought here to determine the mechanisms involved in glucose and insulin-stimulated nuclear shuttling of FoxO1 in pancreatic β cells and its consequences for preproinsulin (Ins1, Ins2) gene expression. |
| 3887 | 21335550 | Constitutively active PI3K or protein kinase B/Akt exerted similar effects, while inhibitors of PI3K, but not of glycogen synthase kinase-3 or p70 S6 kinase, blocked nuclear export. |
| 3888 | 21335550 | FoxO1 overexpression reversed the activation by glucose of pancreatic duodenum homeobox-1 (Pdx1) transcription. |
| 3889 | 21335550 | A 915-bp glucose-responsive Ins2 promoter was inhibited by constitutively active FoxO1, an effect unaltered by simultaneous overexpression of PDX1. |
| 3890 | 21335550 | We conclude that nuclear import of FoxO1 contributes to the suppression of Pdx1 and Ins2 gene expression at low glucose, the latter via a previously unsuspected and direct physical interaction with the Ins2 promoter. |
| 3891 | 21335550 | FoxO1 activity is tightly controlled by phosphatidylinositol 3-kinase (PI3K) signaling, resulting in its phosphorylation and nuclear exclusion. |
| 3892 | 21335550 | We sought here to determine the mechanisms involved in glucose and insulin-stimulated nuclear shuttling of FoxO1 in pancreatic β cells and its consequences for preproinsulin (Ins1, Ins2) gene expression. |
| 3893 | 21335550 | Constitutively active PI3K or protein kinase B/Akt exerted similar effects, while inhibitors of PI3K, but not of glycogen synthase kinase-3 or p70 S6 kinase, blocked nuclear export. |
| 3894 | 21335550 | FoxO1 overexpression reversed the activation by glucose of pancreatic duodenum homeobox-1 (Pdx1) transcription. |
| 3895 | 21335550 | A 915-bp glucose-responsive Ins2 promoter was inhibited by constitutively active FoxO1, an effect unaltered by simultaneous overexpression of PDX1. |
| 3896 | 21335550 | We conclude that nuclear import of FoxO1 contributes to the suppression of Pdx1 and Ins2 gene expression at low glucose, the latter via a previously unsuspected and direct physical interaction with the Ins2 promoter. |
| 3897 | 21393239 | Neutralizing interleukin-1beta (IL-1beta) induces beta-cell survival by maintaining PDX1 protein nuclear localization. |
| 3898 | 21393239 | The transcription factor PDX1 plays a critical role during β-cell development and in glucose-induced insulin gene transcription in adult β-cells. |
| 3899 | 21393239 | In isolated islets from patients with type 2 diabetes and from diabetic mice, we found opposite regulation of insulin and PDX1 mRNA; insulin was decreased in diabetes, but PDX1 was increased. |
| 3900 | 21393239 | This suggests that elevated PDX1 mRNA levels may be insufficient to regulate insulin. |
| 3901 | 21393239 | In contrast, overexpression of either IL-1 receptor antagonist or shuttling-deficient PDX1 restored β-cell survival and function and PDX1 nuclear localization. |
| 3902 | 21393239 | Our results show that nuclear localization of PDX1 is essential for a functional β-cell and provides a novel mechanism of the protective effect of IL-1 receptor antagonist on β-cell survival and function. |
| 3903 | 21393239 | Neutralizing interleukin-1beta (IL-1beta) induces beta-cell survival by maintaining PDX1 protein nuclear localization. |
| 3904 | 21393239 | The transcription factor PDX1 plays a critical role during β-cell development and in glucose-induced insulin gene transcription in adult β-cells. |
| 3905 | 21393239 | In isolated islets from patients with type 2 diabetes and from diabetic mice, we found opposite regulation of insulin and PDX1 mRNA; insulin was decreased in diabetes, but PDX1 was increased. |
| 3906 | 21393239 | This suggests that elevated PDX1 mRNA levels may be insufficient to regulate insulin. |
| 3907 | 21393239 | In contrast, overexpression of either IL-1 receptor antagonist or shuttling-deficient PDX1 restored β-cell survival and function and PDX1 nuclear localization. |
| 3908 | 21393239 | Our results show that nuclear localization of PDX1 is essential for a functional β-cell and provides a novel mechanism of the protective effect of IL-1 receptor antagonist on β-cell survival and function. |
| 3909 | 21393239 | Neutralizing interleukin-1beta (IL-1beta) induces beta-cell survival by maintaining PDX1 protein nuclear localization. |
| 3910 | 21393239 | The transcription factor PDX1 plays a critical role during β-cell development and in glucose-induced insulin gene transcription in adult β-cells. |
| 3911 | 21393239 | In isolated islets from patients with type 2 diabetes and from diabetic mice, we found opposite regulation of insulin and PDX1 mRNA; insulin was decreased in diabetes, but PDX1 was increased. |
| 3912 | 21393239 | This suggests that elevated PDX1 mRNA levels may be insufficient to regulate insulin. |
| 3913 | 21393239 | In contrast, overexpression of either IL-1 receptor antagonist or shuttling-deficient PDX1 restored β-cell survival and function and PDX1 nuclear localization. |
| 3914 | 21393239 | Our results show that nuclear localization of PDX1 is essential for a functional β-cell and provides a novel mechanism of the protective effect of IL-1 receptor antagonist on β-cell survival and function. |
| 3915 | 21393239 | Neutralizing interleukin-1beta (IL-1beta) induces beta-cell survival by maintaining PDX1 protein nuclear localization. |
| 3916 | 21393239 | The transcription factor PDX1 plays a critical role during β-cell development and in glucose-induced insulin gene transcription in adult β-cells. |
| 3917 | 21393239 | In isolated islets from patients with type 2 diabetes and from diabetic mice, we found opposite regulation of insulin and PDX1 mRNA; insulin was decreased in diabetes, but PDX1 was increased. |
| 3918 | 21393239 | This suggests that elevated PDX1 mRNA levels may be insufficient to regulate insulin. |
| 3919 | 21393239 | In contrast, overexpression of either IL-1 receptor antagonist or shuttling-deficient PDX1 restored β-cell survival and function and PDX1 nuclear localization. |
| 3920 | 21393239 | Our results show that nuclear localization of PDX1 is essential for a functional β-cell and provides a novel mechanism of the protective effect of IL-1 receptor antagonist on β-cell survival and function. |
| 3921 | 21393239 | Neutralizing interleukin-1beta (IL-1beta) induces beta-cell survival by maintaining PDX1 protein nuclear localization. |
| 3922 | 21393239 | The transcription factor PDX1 plays a critical role during β-cell development and in glucose-induced insulin gene transcription in adult β-cells. |
| 3923 | 21393239 | In isolated islets from patients with type 2 diabetes and from diabetic mice, we found opposite regulation of insulin and PDX1 mRNA; insulin was decreased in diabetes, but PDX1 was increased. |
| 3924 | 21393239 | This suggests that elevated PDX1 mRNA levels may be insufficient to regulate insulin. |
| 3925 | 21393239 | In contrast, overexpression of either IL-1 receptor antagonist or shuttling-deficient PDX1 restored β-cell survival and function and PDX1 nuclear localization. |
| 3926 | 21393239 | Our results show that nuclear localization of PDX1 is essential for a functional β-cell and provides a novel mechanism of the protective effect of IL-1 receptor antagonist on β-cell survival and function. |
| 3927 | 21393239 | Neutralizing interleukin-1beta (IL-1beta) induces beta-cell survival by maintaining PDX1 protein nuclear localization. |
| 3928 | 21393239 | The transcription factor PDX1 plays a critical role during β-cell development and in glucose-induced insulin gene transcription in adult β-cells. |
| 3929 | 21393239 | In isolated islets from patients with type 2 diabetes and from diabetic mice, we found opposite regulation of insulin and PDX1 mRNA; insulin was decreased in diabetes, but PDX1 was increased. |
| 3930 | 21393239 | This suggests that elevated PDX1 mRNA levels may be insufficient to regulate insulin. |
| 3931 | 21393239 | In contrast, overexpression of either IL-1 receptor antagonist or shuttling-deficient PDX1 restored β-cell survival and function and PDX1 nuclear localization. |
| 3932 | 21393239 | Our results show that nuclear localization of PDX1 is essential for a functional β-cell and provides a novel mechanism of the protective effect of IL-1 receptor antagonist on β-cell survival and function. |
| 3933 | 21399612 | Here, we demonstrate that RB associates with and stabilizes pancreatic duodenal homeobox-1 (Pdx-1) that is essential for embryonic pancreas development and adult β-cell function. |
| 3934 | 21399612 | These results demonstrate an unanticipated regulatory mechanism for pancreatic development and β-cell function, which involves RB-mediated stabilization of the pancreas-specific transcription factor Pdx-1. |
| 3935 | 21399612 | Here, we demonstrate that RB associates with and stabilizes pancreatic duodenal homeobox-1 (Pdx-1) that is essential for embryonic pancreas development and adult β-cell function. |
| 3936 | 21399612 | These results demonstrate an unanticipated regulatory mechanism for pancreatic development and β-cell function, which involves RB-mediated stabilization of the pancreas-specific transcription factor Pdx-1. |
| 3937 | 21457125 | Islet-homed CD45-negative donor cells identified by sex chromosomes downregulated GFP, expressed PDX-1 and proinsulin, and converted the hormone precursor to insulin. |
| 3938 | 21540283 | Pancreatic and duodenal homeobox 1 (PDX1), a key pancreatic transcription factor, regulates insulin along with targets involved in insulin processing and secretion. |
| 3939 | 21540283 | These findings demonstrate roles for the PDX1 target ERO1lβ in maintaining insulin content and regulating cell survival during ER stress. |
| 3940 | 21540283 | Pancreatic and duodenal homeobox 1 (PDX1), a key pancreatic transcription factor, regulates insulin along with targets involved in insulin processing and secretion. |
| 3941 | 21540283 | These findings demonstrate roles for the PDX1 target ERO1lβ in maintaining insulin content and regulating cell survival during ER stress. |
| 3942 | 21571864 | Glucokinase (GK) plays a critical role in controlling blood glucose; GK activators have been shown to stimulate insulin secretion acutely both in vitro and in vivo. |
| 3943 | 21571864 | Chronic culture of mouse islets with GKA71 in 5 mmol/l glucose significantly increased the expression of insulin, IAPP, GLUT2, PDX1 and PC1 and decreased the expression of C/EBPβ compared with 5 mmol/l glucose alone. |
| 3944 | 21571864 | Similar increases were shown for insulin, GLUT2, IAPP and PC1 in chronically treated rat islets. |
| 3945 | 21633187 | Using a novel Pdx1/Ins1 dual fluorescent reporter lentiviral vector, we previously found that individual adult human and mouse β-cells exist in at least two differentiation states distinguishable by the activation of the rat Ins1 promoter and performed the first real-time imaging of the maturation of individual cultured β-cells. |
| 3946 | 21633187 | Gene expression profiling of FACS purified immature Pdx1 (+) /Ins1 (low) cells and mature Pdx1 (high) /Ins1 (high ) cells from cultures of human islets, mouse islets and MIN6 cells revealed that Pdx1 (+) /Ins1 (low) cells are enriched for multiple genes associated with β-cell development/progenitor cells, proliferation, apoptosis, as well as genes coding for other islet cell hormones such as glucagon. |
| 3947 | 21633187 | Using a novel Pdx1/Ins1 dual fluorescent reporter lentiviral vector, we previously found that individual adult human and mouse β-cells exist in at least two differentiation states distinguishable by the activation of the rat Ins1 promoter and performed the first real-time imaging of the maturation of individual cultured β-cells. |
| 3948 | 21633187 | Gene expression profiling of FACS purified immature Pdx1 (+) /Ins1 (low) cells and mature Pdx1 (high) /Ins1 (high ) cells from cultures of human islets, mouse islets and MIN6 cells revealed that Pdx1 (+) /Ins1 (low) cells are enriched for multiple genes associated with β-cell development/progenitor cells, proliferation, apoptosis, as well as genes coding for other islet cell hormones such as glucagon. |
| 3949 | 21738894 | Adenoviruses Expressing PDX-1, BETA2/NeuroD and MafA Induces the Transdifferentiation of Porcine Neonatal Pancreas Cell Clusters and Adult Pig Pancreatic Cells into Beta-Cells. |
| 3950 | 21765243 | Human placental lactogen (hPL-A) activates signaling pathways linked to cell survival and improves insulin secretion in human pancreatic islets. |
| 3951 | 21765243 | Among factors with mitogenic activity on pancreatic β-cells, human placental lactogen (hPL) showed stronger activity when compared to the other lactogen hormones: growth hormone (GH) and prolactin (PRL). |
| 3952 | 21765243 | Indeed, the antiapoptotic role of hPL-A was mediated by PI3K, p38 and it was independent by PKA, Erk1/2. |
| 3953 | 21765243 | Moreover, hPL-A induced PDX-1 intracellular expression, improving beta cell activity and ameliorating insulin secretion in response to high glucose stimulation. |
| 3954 | 21773756 | Immunofluorescence staining for chromogranin, insulin, proinsulin, PDX1, glucagon, and cytokeratins confirmed these structures to be composed of chromogranin-positive endocrine cells which included both β-cells and α-cells. |
| 3955 | 21782317 | The serum-free protocol developed in this study resulted in the differentiation of cells into definitive endoderm, pancreatic foregut, pancreatic endoderm and, finally, pancreatic endocrine cells, which expressed the marker genes SOX17, PDX1, NGN3, NKX6.1, INS, GCG, and PPY, respectively. |
| 3956 | 21782317 | Detection of the expression of the gap junction-related gene connexin-36 (CX36) using RT-PCR provided conclusive evidence for insulin-producing cell differentiation. |
| 3957 | 21799688 | Furthermore, SG significantly increased the number and volume of beta cells in the Islets of Langerhans and promoted peroxisome proliferator-activated receptor gamma and pancreatic duodenal homeobox 1 expressions in pancreatic tissues. |
| 3958 | 21799688 | This effect may possibly be involved in enhancing beta-cell regeneration and promoting insulin secretion by targeting PPARγ and PDX-1. |
| 3959 | 21804373 | Effects of Combined Epidermal Growth Factor and Gastrin on PDX1 Expression in Experimental Type 1 Diabetic Rats. |
| 3960 | 21804373 | INTRODUCTION:: The aim of this study was to investigate whether combined epidermal growth factor (EGF) and gastrin can correct the hyperglycemia induced by streptozotocin (STZ) in rats and to determine the involvement of the transcription factor pancreatic and duodenal homeobox 1 (PDX1) in this process. |
| 3961 | 21804373 | The mRNA and protein levels of insulin and PDX1 were determined by real-time reverse transcriptase polymerase chain reaction and immunohistochemistry. |
| 3962 | 21804373 | RESULTS:: The combined administration of EGF and gastrin efficiently reversed the hyperglycemia induced by STZ. |
| 3963 | 21804373 | Elevated insulin concentration was detected in diabetic rats treated with EGF plus gastrin. |
| 3964 | 21804373 | The authors also found that both insulin and PDX1 expression were reduced in STZ-treated rats. |
| 3965 | 21804373 | Interestingly, the combination treatment also significantly enhanced the mRNA levels of insulin and PDX1, and that of their protein products. |
| 3966 | 21804373 | CONCLUSIONS:: Therapy with EGF plus gastrin corrected hyperglycemia and maintained insulin content in STZ-induced diabetic rats via up-regulation of PDX1 expression, suggesting that this combination treatment may provide a valuable approach for pancreatic islet neogenesis in vivo. |
| 3967 | 21804373 | Effects of Combined Epidermal Growth Factor and Gastrin on PDX1 Expression in Experimental Type 1 Diabetic Rats. |
| 3968 | 21804373 | INTRODUCTION:: The aim of this study was to investigate whether combined epidermal growth factor (EGF) and gastrin can correct the hyperglycemia induced by streptozotocin (STZ) in rats and to determine the involvement of the transcription factor pancreatic and duodenal homeobox 1 (PDX1) in this process. |
| 3969 | 21804373 | The mRNA and protein levels of insulin and PDX1 were determined by real-time reverse transcriptase polymerase chain reaction and immunohistochemistry. |
| 3970 | 21804373 | RESULTS:: The combined administration of EGF and gastrin efficiently reversed the hyperglycemia induced by STZ. |
| 3971 | 21804373 | Elevated insulin concentration was detected in diabetic rats treated with EGF plus gastrin. |
| 3972 | 21804373 | The authors also found that both insulin and PDX1 expression were reduced in STZ-treated rats. |
| 3973 | 21804373 | Interestingly, the combination treatment also significantly enhanced the mRNA levels of insulin and PDX1, and that of their protein products. |
| 3974 | 21804373 | CONCLUSIONS:: Therapy with EGF plus gastrin corrected hyperglycemia and maintained insulin content in STZ-induced diabetic rats via up-regulation of PDX1 expression, suggesting that this combination treatment may provide a valuable approach for pancreatic islet neogenesis in vivo. |
| 3975 | 21804373 | Effects of Combined Epidermal Growth Factor and Gastrin on PDX1 Expression in Experimental Type 1 Diabetic Rats. |
| 3976 | 21804373 | INTRODUCTION:: The aim of this study was to investigate whether combined epidermal growth factor (EGF) and gastrin can correct the hyperglycemia induced by streptozotocin (STZ) in rats and to determine the involvement of the transcription factor pancreatic and duodenal homeobox 1 (PDX1) in this process. |
| 3977 | 21804373 | The mRNA and protein levels of insulin and PDX1 were determined by real-time reverse transcriptase polymerase chain reaction and immunohistochemistry. |
| 3978 | 21804373 | RESULTS:: The combined administration of EGF and gastrin efficiently reversed the hyperglycemia induced by STZ. |
| 3979 | 21804373 | Elevated insulin concentration was detected in diabetic rats treated with EGF plus gastrin. |
| 3980 | 21804373 | The authors also found that both insulin and PDX1 expression were reduced in STZ-treated rats. |
| 3981 | 21804373 | Interestingly, the combination treatment also significantly enhanced the mRNA levels of insulin and PDX1, and that of their protein products. |
| 3982 | 21804373 | CONCLUSIONS:: Therapy with EGF plus gastrin corrected hyperglycemia and maintained insulin content in STZ-induced diabetic rats via up-regulation of PDX1 expression, suggesting that this combination treatment may provide a valuable approach for pancreatic islet neogenesis in vivo. |
| 3983 | 21804373 | Effects of Combined Epidermal Growth Factor and Gastrin on PDX1 Expression in Experimental Type 1 Diabetic Rats. |
| 3984 | 21804373 | INTRODUCTION:: The aim of this study was to investigate whether combined epidermal growth factor (EGF) and gastrin can correct the hyperglycemia induced by streptozotocin (STZ) in rats and to determine the involvement of the transcription factor pancreatic and duodenal homeobox 1 (PDX1) in this process. |
| 3985 | 21804373 | The mRNA and protein levels of insulin and PDX1 were determined by real-time reverse transcriptase polymerase chain reaction and immunohistochemistry. |
| 3986 | 21804373 | RESULTS:: The combined administration of EGF and gastrin efficiently reversed the hyperglycemia induced by STZ. |
| 3987 | 21804373 | Elevated insulin concentration was detected in diabetic rats treated with EGF plus gastrin. |
| 3988 | 21804373 | The authors also found that both insulin and PDX1 expression were reduced in STZ-treated rats. |
| 3989 | 21804373 | Interestingly, the combination treatment also significantly enhanced the mRNA levels of insulin and PDX1, and that of their protein products. |
| 3990 | 21804373 | CONCLUSIONS:: Therapy with EGF plus gastrin corrected hyperglycemia and maintained insulin content in STZ-induced diabetic rats via up-regulation of PDX1 expression, suggesting that this combination treatment may provide a valuable approach for pancreatic islet neogenesis in vivo. |
| 3991 | 21804373 | Effects of Combined Epidermal Growth Factor and Gastrin on PDX1 Expression in Experimental Type 1 Diabetic Rats. |
| 3992 | 21804373 | INTRODUCTION:: The aim of this study was to investigate whether combined epidermal growth factor (EGF) and gastrin can correct the hyperglycemia induced by streptozotocin (STZ) in rats and to determine the involvement of the transcription factor pancreatic and duodenal homeobox 1 (PDX1) in this process. |
| 3993 | 21804373 | The mRNA and protein levels of insulin and PDX1 were determined by real-time reverse transcriptase polymerase chain reaction and immunohistochemistry. |
| 3994 | 21804373 | RESULTS:: The combined administration of EGF and gastrin efficiently reversed the hyperglycemia induced by STZ. |
| 3995 | 21804373 | Elevated insulin concentration was detected in diabetic rats treated with EGF plus gastrin. |
| 3996 | 21804373 | The authors also found that both insulin and PDX1 expression were reduced in STZ-treated rats. |
| 3997 | 21804373 | Interestingly, the combination treatment also significantly enhanced the mRNA levels of insulin and PDX1, and that of their protein products. |
| 3998 | 21804373 | CONCLUSIONS:: Therapy with EGF plus gastrin corrected hyperglycemia and maintained insulin content in STZ-induced diabetic rats via up-regulation of PDX1 expression, suggesting that this combination treatment may provide a valuable approach for pancreatic islet neogenesis in vivo. |
| 3999 | 21804373 | Effects of Combined Epidermal Growth Factor and Gastrin on PDX1 Expression in Experimental Type 1 Diabetic Rats. |
| 4000 | 21804373 | INTRODUCTION:: The aim of this study was to investigate whether combined epidermal growth factor (EGF) and gastrin can correct the hyperglycemia induced by streptozotocin (STZ) in rats and to determine the involvement of the transcription factor pancreatic and duodenal homeobox 1 (PDX1) in this process. |
| 4001 | 21804373 | The mRNA and protein levels of insulin and PDX1 were determined by real-time reverse transcriptase polymerase chain reaction and immunohistochemistry. |
| 4002 | 21804373 | RESULTS:: The combined administration of EGF and gastrin efficiently reversed the hyperglycemia induced by STZ. |
| 4003 | 21804373 | Elevated insulin concentration was detected in diabetic rats treated with EGF plus gastrin. |
| 4004 | 21804373 | The authors also found that both insulin and PDX1 expression were reduced in STZ-treated rats. |
| 4005 | 21804373 | Interestingly, the combination treatment also significantly enhanced the mRNA levels of insulin and PDX1, and that of their protein products. |
| 4006 | 21804373 | CONCLUSIONS:: Therapy with EGF plus gastrin corrected hyperglycemia and maintained insulin content in STZ-induced diabetic rats via up-regulation of PDX1 expression, suggesting that this combination treatment may provide a valuable approach for pancreatic islet neogenesis in vivo. |
| 4007 | 21814221 | We genotyped 91 polymorphisms in 19 genes (ABCC8, HNF1A, HNF1B, HNF4A, INS, INSM1, ISL1, KCNJ11, MAFA, MNX1, NEUROD1, NEUROG3, NKX2.2, NKX6.1, PAX4, PAX6, PDX1, USF1 and WFS1) in 2025 unrelated North Indians of Indo-European ethnicity comprising of 1019 diabetic and 1006 non-diabetic subjects. |
| 4008 | 21814221 | Variants in USF1, ABCC8, ISL1 and KCNJ11 showed nominal association, while haplotypes in these genes were significantly associated. rs3812704 upstream of NEUROG3 significantly increased risk for type 2 diabetes in normal-weight/lean subjects (OR=1.68 (95%CI 1.25-2.24), P=4.9 × 10(-4)). |
| 4009 | 21821004 | ATF3 represses PDX-1 expression in pancreatic β-cells. |
| 4010 | 21821004 | In this study, we analyzed the mouse PDX-1 promoter to characterize the effects of ATF3 on PDX-1 expression in pancreatic β-cells. |
| 4011 | 21821004 | Both thapsigargin treatment, an inducer of ER stress, and ATF3 expression decreased PDX-1 expression in pancreatic β-cells, MIN6N8. |
| 4012 | 21821004 | Transfection studies with 5' deleted-reporters showed that ATF3 repressed the activity of 0.9Kb PDX-1 promoter, whereas it did not affect the activity of 0.7 Kb PDX-1 promoter, suggesting that ATF3 responsive element is located between the -903 and -702. |
| 4013 | 21821004 | Moreover, mutation of the putative ATF/CRE site between -752 and -745 abrogated ATF3-mediated transrepression of the PDX-1 promoter. |
| 4014 | 21821004 | PDX-1 was decreased in MIN6N8 cells treated with high glucose or high palmitate, whereas ATF3 was increased, indicating that ATF3 plays a role in hyperglycemia or hyperlipidemia-mediated downregulation of PDX-1 expression. |
| 4015 | 21821004 | Collectively, these results demonstrate that ATF3 represses PDX-1 expression via binding to an ATF3-responsive element in its promoter, which plays an important role in suppression of pancreatic β-cells function. |
| 4016 | 21821004 | ATF3 represses PDX-1 expression in pancreatic β-cells. |
| 4017 | 21821004 | In this study, we analyzed the mouse PDX-1 promoter to characterize the effects of ATF3 on PDX-1 expression in pancreatic β-cells. |
| 4018 | 21821004 | Both thapsigargin treatment, an inducer of ER stress, and ATF3 expression decreased PDX-1 expression in pancreatic β-cells, MIN6N8. |
| 4019 | 21821004 | Transfection studies with 5' deleted-reporters showed that ATF3 repressed the activity of 0.9Kb PDX-1 promoter, whereas it did not affect the activity of 0.7 Kb PDX-1 promoter, suggesting that ATF3 responsive element is located between the -903 and -702. |
| 4020 | 21821004 | Moreover, mutation of the putative ATF/CRE site between -752 and -745 abrogated ATF3-mediated transrepression of the PDX-1 promoter. |
| 4021 | 21821004 | PDX-1 was decreased in MIN6N8 cells treated with high glucose or high palmitate, whereas ATF3 was increased, indicating that ATF3 plays a role in hyperglycemia or hyperlipidemia-mediated downregulation of PDX-1 expression. |
| 4022 | 21821004 | Collectively, these results demonstrate that ATF3 represses PDX-1 expression via binding to an ATF3-responsive element in its promoter, which plays an important role in suppression of pancreatic β-cells function. |
| 4023 | 21821004 | ATF3 represses PDX-1 expression in pancreatic β-cells. |
| 4024 | 21821004 | In this study, we analyzed the mouse PDX-1 promoter to characterize the effects of ATF3 on PDX-1 expression in pancreatic β-cells. |
| 4025 | 21821004 | Both thapsigargin treatment, an inducer of ER stress, and ATF3 expression decreased PDX-1 expression in pancreatic β-cells, MIN6N8. |
| 4026 | 21821004 | Transfection studies with 5' deleted-reporters showed that ATF3 repressed the activity of 0.9Kb PDX-1 promoter, whereas it did not affect the activity of 0.7 Kb PDX-1 promoter, suggesting that ATF3 responsive element is located between the -903 and -702. |
| 4027 | 21821004 | Moreover, mutation of the putative ATF/CRE site between -752 and -745 abrogated ATF3-mediated transrepression of the PDX-1 promoter. |
| 4028 | 21821004 | PDX-1 was decreased in MIN6N8 cells treated with high glucose or high palmitate, whereas ATF3 was increased, indicating that ATF3 plays a role in hyperglycemia or hyperlipidemia-mediated downregulation of PDX-1 expression. |
| 4029 | 21821004 | Collectively, these results demonstrate that ATF3 represses PDX-1 expression via binding to an ATF3-responsive element in its promoter, which plays an important role in suppression of pancreatic β-cells function. |
| 4030 | 21821004 | ATF3 represses PDX-1 expression in pancreatic β-cells. |
| 4031 | 21821004 | In this study, we analyzed the mouse PDX-1 promoter to characterize the effects of ATF3 on PDX-1 expression in pancreatic β-cells. |
| 4032 | 21821004 | Both thapsigargin treatment, an inducer of ER stress, and ATF3 expression decreased PDX-1 expression in pancreatic β-cells, MIN6N8. |
| 4033 | 21821004 | Transfection studies with 5' deleted-reporters showed that ATF3 repressed the activity of 0.9Kb PDX-1 promoter, whereas it did not affect the activity of 0.7 Kb PDX-1 promoter, suggesting that ATF3 responsive element is located between the -903 and -702. |
| 4034 | 21821004 | Moreover, mutation of the putative ATF/CRE site between -752 and -745 abrogated ATF3-mediated transrepression of the PDX-1 promoter. |
| 4035 | 21821004 | PDX-1 was decreased in MIN6N8 cells treated with high glucose or high palmitate, whereas ATF3 was increased, indicating that ATF3 plays a role in hyperglycemia or hyperlipidemia-mediated downregulation of PDX-1 expression. |
| 4036 | 21821004 | Collectively, these results demonstrate that ATF3 represses PDX-1 expression via binding to an ATF3-responsive element in its promoter, which plays an important role in suppression of pancreatic β-cells function. |
| 4037 | 21821004 | ATF3 represses PDX-1 expression in pancreatic β-cells. |
| 4038 | 21821004 | In this study, we analyzed the mouse PDX-1 promoter to characterize the effects of ATF3 on PDX-1 expression in pancreatic β-cells. |
| 4039 | 21821004 | Both thapsigargin treatment, an inducer of ER stress, and ATF3 expression decreased PDX-1 expression in pancreatic β-cells, MIN6N8. |
| 4040 | 21821004 | Transfection studies with 5' deleted-reporters showed that ATF3 repressed the activity of 0.9Kb PDX-1 promoter, whereas it did not affect the activity of 0.7 Kb PDX-1 promoter, suggesting that ATF3 responsive element is located between the -903 and -702. |
| 4041 | 21821004 | Moreover, mutation of the putative ATF/CRE site between -752 and -745 abrogated ATF3-mediated transrepression of the PDX-1 promoter. |
| 4042 | 21821004 | PDX-1 was decreased in MIN6N8 cells treated with high glucose or high palmitate, whereas ATF3 was increased, indicating that ATF3 plays a role in hyperglycemia or hyperlipidemia-mediated downregulation of PDX-1 expression. |
| 4043 | 21821004 | Collectively, these results demonstrate that ATF3 represses PDX-1 expression via binding to an ATF3-responsive element in its promoter, which plays an important role in suppression of pancreatic β-cells function. |
| 4044 | 21821004 | ATF3 represses PDX-1 expression in pancreatic β-cells. |
| 4045 | 21821004 | In this study, we analyzed the mouse PDX-1 promoter to characterize the effects of ATF3 on PDX-1 expression in pancreatic β-cells. |
| 4046 | 21821004 | Both thapsigargin treatment, an inducer of ER stress, and ATF3 expression decreased PDX-1 expression in pancreatic β-cells, MIN6N8. |
| 4047 | 21821004 | Transfection studies with 5' deleted-reporters showed that ATF3 repressed the activity of 0.9Kb PDX-1 promoter, whereas it did not affect the activity of 0.7 Kb PDX-1 promoter, suggesting that ATF3 responsive element is located between the -903 and -702. |
| 4048 | 21821004 | Moreover, mutation of the putative ATF/CRE site between -752 and -745 abrogated ATF3-mediated transrepression of the PDX-1 promoter. |
| 4049 | 21821004 | PDX-1 was decreased in MIN6N8 cells treated with high glucose or high palmitate, whereas ATF3 was increased, indicating that ATF3 plays a role in hyperglycemia or hyperlipidemia-mediated downregulation of PDX-1 expression. |
| 4050 | 21821004 | Collectively, these results demonstrate that ATF3 represses PDX-1 expression via binding to an ATF3-responsive element in its promoter, which plays an important role in suppression of pancreatic β-cells function. |
| 4051 | 21821004 | ATF3 represses PDX-1 expression in pancreatic β-cells. |
| 4052 | 21821004 | In this study, we analyzed the mouse PDX-1 promoter to characterize the effects of ATF3 on PDX-1 expression in pancreatic β-cells. |
| 4053 | 21821004 | Both thapsigargin treatment, an inducer of ER stress, and ATF3 expression decreased PDX-1 expression in pancreatic β-cells, MIN6N8. |
| 4054 | 21821004 | Transfection studies with 5' deleted-reporters showed that ATF3 repressed the activity of 0.9Kb PDX-1 promoter, whereas it did not affect the activity of 0.7 Kb PDX-1 promoter, suggesting that ATF3 responsive element is located between the -903 and -702. |
| 4055 | 21821004 | Moreover, mutation of the putative ATF/CRE site between -752 and -745 abrogated ATF3-mediated transrepression of the PDX-1 promoter. |
| 4056 | 21821004 | PDX-1 was decreased in MIN6N8 cells treated with high glucose or high palmitate, whereas ATF3 was increased, indicating that ATF3 plays a role in hyperglycemia or hyperlipidemia-mediated downregulation of PDX-1 expression. |
| 4057 | 21821004 | Collectively, these results demonstrate that ATF3 represses PDX-1 expression via binding to an ATF3-responsive element in its promoter, which plays an important role in suppression of pancreatic β-cells function. |
| 4058 | 21829703 | Based on in vitro studies it has been suggested that Sox9 controls expression of a network of important developmental regulators, including Tcf2/MODY5, Hnf6, and Foxa2, in pancreatic progenitor cells. |
| 4059 | 21829703 | Employing two genetic models of temporally-controlled Sox9 inactivation in pancreatic progenitor cells, we demonstrate that contrary to in vitro findings, Sox9 is not required for Tcf2, Hnf6, or Foxa2 expression in vivo. |
| 4060 | 21829703 | Moreover, our analysis revealed a novel role for Sox9 in maintaining the expression of Pdx1/MODY4, which is an important transcriptional regulator of beta-cell development. |
| 4061 | 21829703 | Endocrine islets from mice with reduced Sox9 gene dosage exhibited normal glucose stimulated insulin secretion. |
| 4062 | 21829703 | Our findings show Sox9 plays an important role in endocrine development by maintaining Ngn3 and Pdx1 expression. |
| 4063 | 21829703 | Based on in vitro studies it has been suggested that Sox9 controls expression of a network of important developmental regulators, including Tcf2/MODY5, Hnf6, and Foxa2, in pancreatic progenitor cells. |
| 4064 | 21829703 | Employing two genetic models of temporally-controlled Sox9 inactivation in pancreatic progenitor cells, we demonstrate that contrary to in vitro findings, Sox9 is not required for Tcf2, Hnf6, or Foxa2 expression in vivo. |
| 4065 | 21829703 | Moreover, our analysis revealed a novel role for Sox9 in maintaining the expression of Pdx1/MODY4, which is an important transcriptional regulator of beta-cell development. |
| 4066 | 21829703 | Endocrine islets from mice with reduced Sox9 gene dosage exhibited normal glucose stimulated insulin secretion. |
| 4067 | 21829703 | Our findings show Sox9 plays an important role in endocrine development by maintaining Ngn3 and Pdx1 expression. |
| 4068 | 21837359 | Differentiation of PDX1 gene-modified human umbilical cord mesenchymal stem cells into insulin-producing cells in vitro. |
| 4069 | 21837359 | In this study, MSCs from human umbilical cord were differentiated into functional insulin-producing cells in vitro by introduction of the pancreatic and duodenal homeobox factor 1 (PDX1) and in the presence of induction factors. |
| 4070 | 21837359 | In conclusion, our results demonstrated that PDX1 gene-modified human umbilical cord mesenchymal stem cells could be differentiated into insulin-producing cells in vitro. |
| 4071 | 21837359 | Differentiation of PDX1 gene-modified human umbilical cord mesenchymal stem cells into insulin-producing cells in vitro. |
| 4072 | 21837359 | In this study, MSCs from human umbilical cord were differentiated into functional insulin-producing cells in vitro by introduction of the pancreatic and duodenal homeobox factor 1 (PDX1) and in the presence of induction factors. |
| 4073 | 21837359 | In conclusion, our results demonstrated that PDX1 gene-modified human umbilical cord mesenchymal stem cells could be differentiated into insulin-producing cells in vitro. |
| 4074 | 21837359 | Differentiation of PDX1 gene-modified human umbilical cord mesenchymal stem cells into insulin-producing cells in vitro. |
| 4075 | 21837359 | In this study, MSCs from human umbilical cord were differentiated into functional insulin-producing cells in vitro by introduction of the pancreatic and duodenal homeobox factor 1 (PDX1) and in the presence of induction factors. |
| 4076 | 21837359 | In conclusion, our results demonstrated that PDX1 gene-modified human umbilical cord mesenchymal stem cells could be differentiated into insulin-producing cells in vitro. |
| 4077 | 21855631 | In this study, we describe the roles of growth factors bFGF, BMP4 and Activin A in early hESC fate determination. |
| 4078 | 21855631 | The entire differentiation process is carried out in serum-free chemically-defined media (CDM) and results in reliable and robust induction of pancreatic endoderm cells, marked by PDX1, and cell clusters co-expressing markers characteristic of beta cells, including PDX1 and insulin/C-peptide. |
| 4079 | 21855631 | Varying the combinations of growth factors, we found that treatment of hESCs with bFGF, Activin A and BMP4 (FAB) together for 3-4days resulted in strong induction of primitive-streak and definitive endoderm-associated genes, including MIXL1, GSC, SOX17 and FOXA2. |
| 4080 | 21855631 | Early proliferative foregut endoderm and pancreatic lineage cells marked by PDX1, FOXA2 and SOX9 expression are specified in EBs made from FAB-treated hESCs, but not from Activin A alone treated cells. |
| 4081 | 21855631 | Further differentiation occurs after EBs are embedded in Matrigel and cultured in serum-free media containing insulin, transferrin, selenium, FGF7, nicotinamide, islet neogenesis associated peptide (INGAP) and exendin-4, a long acting GLP-1 agonist. 21-28days after embedding, PDX1 gene expression levels are comparable to those of human islets used for transplantation, and many PDX1(+) clusters are formed. |
| 4082 | 21855631 | Almost all cells in PDX1(+) clusters co-express FOXA2, HNF1ß, HNF6 and SOX9 proteins, and many cells also express CPA1, NKX6.1 and PTF1a. |
| 4083 | 21855631 | In this study, we describe the roles of growth factors bFGF, BMP4 and Activin A in early hESC fate determination. |
| 4084 | 21855631 | The entire differentiation process is carried out in serum-free chemically-defined media (CDM) and results in reliable and robust induction of pancreatic endoderm cells, marked by PDX1, and cell clusters co-expressing markers characteristic of beta cells, including PDX1 and insulin/C-peptide. |
| 4085 | 21855631 | Varying the combinations of growth factors, we found that treatment of hESCs with bFGF, Activin A and BMP4 (FAB) together for 3-4days resulted in strong induction of primitive-streak and definitive endoderm-associated genes, including MIXL1, GSC, SOX17 and FOXA2. |
| 4086 | 21855631 | Early proliferative foregut endoderm and pancreatic lineage cells marked by PDX1, FOXA2 and SOX9 expression are specified in EBs made from FAB-treated hESCs, but not from Activin A alone treated cells. |
| 4087 | 21855631 | Further differentiation occurs after EBs are embedded in Matrigel and cultured in serum-free media containing insulin, transferrin, selenium, FGF7, nicotinamide, islet neogenesis associated peptide (INGAP) and exendin-4, a long acting GLP-1 agonist. 21-28days after embedding, PDX1 gene expression levels are comparable to those of human islets used for transplantation, and many PDX1(+) clusters are formed. |
| 4088 | 21855631 | Almost all cells in PDX1(+) clusters co-express FOXA2, HNF1ß, HNF6 and SOX9 proteins, and many cells also express CPA1, NKX6.1 and PTF1a. |
| 4089 | 21855631 | In this study, we describe the roles of growth factors bFGF, BMP4 and Activin A in early hESC fate determination. |
| 4090 | 21855631 | The entire differentiation process is carried out in serum-free chemically-defined media (CDM) and results in reliable and robust induction of pancreatic endoderm cells, marked by PDX1, and cell clusters co-expressing markers characteristic of beta cells, including PDX1 and insulin/C-peptide. |
| 4091 | 21855631 | Varying the combinations of growth factors, we found that treatment of hESCs with bFGF, Activin A and BMP4 (FAB) together for 3-4days resulted in strong induction of primitive-streak and definitive endoderm-associated genes, including MIXL1, GSC, SOX17 and FOXA2. |
| 4092 | 21855631 | Early proliferative foregut endoderm and pancreatic lineage cells marked by PDX1, FOXA2 and SOX9 expression are specified in EBs made from FAB-treated hESCs, but not from Activin A alone treated cells. |
| 4093 | 21855631 | Further differentiation occurs after EBs are embedded in Matrigel and cultured in serum-free media containing insulin, transferrin, selenium, FGF7, nicotinamide, islet neogenesis associated peptide (INGAP) and exendin-4, a long acting GLP-1 agonist. 21-28days after embedding, PDX1 gene expression levels are comparable to those of human islets used for transplantation, and many PDX1(+) clusters are formed. |
| 4094 | 21855631 | Almost all cells in PDX1(+) clusters co-express FOXA2, HNF1ß, HNF6 and SOX9 proteins, and many cells also express CPA1, NKX6.1 and PTF1a. |
| 4095 | 21855631 | In this study, we describe the roles of growth factors bFGF, BMP4 and Activin A in early hESC fate determination. |
| 4096 | 21855631 | The entire differentiation process is carried out in serum-free chemically-defined media (CDM) and results in reliable and robust induction of pancreatic endoderm cells, marked by PDX1, and cell clusters co-expressing markers characteristic of beta cells, including PDX1 and insulin/C-peptide. |
| 4097 | 21855631 | Varying the combinations of growth factors, we found that treatment of hESCs with bFGF, Activin A and BMP4 (FAB) together for 3-4days resulted in strong induction of primitive-streak and definitive endoderm-associated genes, including MIXL1, GSC, SOX17 and FOXA2. |
| 4098 | 21855631 | Early proliferative foregut endoderm and pancreatic lineage cells marked by PDX1, FOXA2 and SOX9 expression are specified in EBs made from FAB-treated hESCs, but not from Activin A alone treated cells. |
| 4099 | 21855631 | Further differentiation occurs after EBs are embedded in Matrigel and cultured in serum-free media containing insulin, transferrin, selenium, FGF7, nicotinamide, islet neogenesis associated peptide (INGAP) and exendin-4, a long acting GLP-1 agonist. 21-28days after embedding, PDX1 gene expression levels are comparable to those of human islets used for transplantation, and many PDX1(+) clusters are formed. |
| 4100 | 21855631 | Almost all cells in PDX1(+) clusters co-express FOXA2, HNF1ß, HNF6 and SOX9 proteins, and many cells also express CPA1, NKX6.1 and PTF1a. |
| 4101 | 21857924 | TAT-mediated transduction of MafA protein in utero results in enhanced pancreatic insulin expression and changes in islet morphology. |
| 4102 | 21857924 | Alongside Pdx1 and Beta2/NeuroD, the transcription factor MafA has been shown to be instrumental in the maintenance of the beta cell phenotype. |
| 4103 | 21857924 | Indeed, a combination of MafA, Pdx1 and Ngn3 (an upstream regulator of Beta2/NeuroD) was recently reported to lead to the effective reprogramming of acinar cells into insulin-producing beta cells. |
| 4104 | 21857924 | Here we describe a recombinant transducible version of the MafA protein (TAT-MafA) that penetrates across cell membranes with an efficiency of 100% and binds to the insulin promoter in vitro. |
| 4105 | 21857924 | TAT-mediated transduction of MafA protein in utero results in enhanced pancreatic insulin expression and changes in islet morphology. |
| 4106 | 21857924 | Alongside Pdx1 and Beta2/NeuroD, the transcription factor MafA has been shown to be instrumental in the maintenance of the beta cell phenotype. |
| 4107 | 21857924 | Indeed, a combination of MafA, Pdx1 and Ngn3 (an upstream regulator of Beta2/NeuroD) was recently reported to lead to the effective reprogramming of acinar cells into insulin-producing beta cells. |
| 4108 | 21857924 | Here we describe a recombinant transducible version of the MafA protein (TAT-MafA) that penetrates across cell membranes with an efficiency of 100% and binds to the insulin promoter in vitro. |
| 4109 | 21878900 | PAX4, PDX1, GLUT2, and insulin, were all increased in differentiated cells compared to controls. |
| 4110 | 21898210 | RT-PCR was performed on a range of mRNAs, including Pdx1, Npy, Egr1, Pld1, Chgb, InsI, InsII, and Actb in biological triplicate analyses.Reproducible amplification of these mRNAs from MIN6, MIN6 B1, and Vero-PPI cells and their CM suggests that beta cells transcribe and release these mRNAs into their environment. mRNAs secreted from insulin-producing cells into their extracellular environment may have potential as extracellular biomarkers for assessing beta cell mass and function. |
| 4111 | 21915820 | Enhanced differentiation of human adipose tissue-derived stromal cells into insulin-producing cells with glucagon-like peptide-1. |
| 4112 | 21915820 | Here, we report an efficient approach to induce human adipose-derived stromal cells (hADSCs) to differentiate into insulin-producing cells, with glucagon-like peptide-1 (GLP-1). hADSCs were successfully isolated from the adipose tissue, with adipogenic and osteogenic differentiation potency. |
| 4113 | 21915820 | Reverse transcription polymerase chain reaction analysis showed the expression of the pancreas-related genes in the differentiated cells, such as pdx-1, ngn3, insulin, glucagon, somatostatin, glucokinase n and glut2. |
| 4114 | 21915820 | Immunocytochemical analysis showed that the induced cells co-expressed insulin, C-peptide and PDX-1. |
| 4115 | 21915820 | In addition, flow cytometry analysis and ELISA showed that, in the presence of GLP-1, the percentage of insulin-producing cells was increased from 5.9% to 28.0% and the release of insulin increased from 9.53±0.7 pmol/106 cells to 15.86±1.3 pmol/106 cells. |
| 4116 | 21915820 | These results indicated that hADSCs isolated from adipose tissues can be induced to differentiate into insulin-producing cells, which is further enhanced with the treatment of GLP-1. |
| 4117 | 21915820 | Enhanced differentiation of human adipose tissue-derived stromal cells into insulin-producing cells with glucagon-like peptide-1. |
| 4118 | 21915820 | Here, we report an efficient approach to induce human adipose-derived stromal cells (hADSCs) to differentiate into insulin-producing cells, with glucagon-like peptide-1 (GLP-1). hADSCs were successfully isolated from the adipose tissue, with adipogenic and osteogenic differentiation potency. |
| 4119 | 21915820 | Reverse transcription polymerase chain reaction analysis showed the expression of the pancreas-related genes in the differentiated cells, such as pdx-1, ngn3, insulin, glucagon, somatostatin, glucokinase n and glut2. |
| 4120 | 21915820 | Immunocytochemical analysis showed that the induced cells co-expressed insulin, C-peptide and PDX-1. |
| 4121 | 21915820 | In addition, flow cytometry analysis and ELISA showed that, in the presence of GLP-1, the percentage of insulin-producing cells was increased from 5.9% to 28.0% and the release of insulin increased from 9.53±0.7 pmol/106 cells to 15.86±1.3 pmol/106 cells. |
| 4122 | 21915820 | These results indicated that hADSCs isolated from adipose tissues can be induced to differentiate into insulin-producing cells, which is further enhanced with the treatment of GLP-1. |
| 4123 | 21986529 | ATF3 inhibits PDX-1-stimulated transactivation. |
| 4124 | 21986529 | Chronic endoplasmic reticulum (ER) stress leads to β-cell failure via reduction of pancreatic and duodenal homeobox-1 (PDX-1) activity, which contributes to the pathogenesis of type 2 diabetes. |
| 4125 | 21986529 | Previously, we showed that ATF3 downregulates PDX-1 gene expression in MIN6N8 pancreatic β-cells. |
| 4126 | 21986529 | Here, we investigated another role of ATF3 on the regulation of PDX-1 activity. |
| 4127 | 21986529 | ATF3 significantly inhibited PDX-1-stimulated transactivation of reporter plasmid containing promoters for PDX-1 binding element and the PDX-1 target gene glucokinase, which is dependent on C-terminal domain of ATF3. |
| 4128 | 21986529 | ATF3 interacted with PDX-1, and effectively inhibited p300-mediated transcriptional coactivation of the PBE-containing promoter, whereas C-terminal domain-deleted ATF3 did not inhibit the transcoactivation of p300. |
| 4129 | 21986529 | ATF3 decreased the interaction of p300 with PDX-1 in MIN6N8 cells coexpressing PDX-1 and ATF3. |
| 4130 | 21986529 | In addition, chromatin immunoprecipitation analysis demonstrated that both tunicamycin treatment and ATF3 overexpression inhibited the recruitment of p300 to PDX-1 on the insulin promoter in MIN6N8 cells. |
| 4131 | 21986529 | Taken together, these results suggest that ATF3 inhibits PDX-1-mediated transactivation through the inhibition of p300-stimulated coactivation, which may lead to β-cell dysfunction by ER stress. |
| 4132 | 21986529 | ATF3 inhibits PDX-1-stimulated transactivation. |
| 4133 | 21986529 | Chronic endoplasmic reticulum (ER) stress leads to β-cell failure via reduction of pancreatic and duodenal homeobox-1 (PDX-1) activity, which contributes to the pathogenesis of type 2 diabetes. |
| 4134 | 21986529 | Previously, we showed that ATF3 downregulates PDX-1 gene expression in MIN6N8 pancreatic β-cells. |
| 4135 | 21986529 | Here, we investigated another role of ATF3 on the regulation of PDX-1 activity. |
| 4136 | 21986529 | ATF3 significantly inhibited PDX-1-stimulated transactivation of reporter plasmid containing promoters for PDX-1 binding element and the PDX-1 target gene glucokinase, which is dependent on C-terminal domain of ATF3. |
| 4137 | 21986529 | ATF3 interacted with PDX-1, and effectively inhibited p300-mediated transcriptional coactivation of the PBE-containing promoter, whereas C-terminal domain-deleted ATF3 did not inhibit the transcoactivation of p300. |
| 4138 | 21986529 | ATF3 decreased the interaction of p300 with PDX-1 in MIN6N8 cells coexpressing PDX-1 and ATF3. |
| 4139 | 21986529 | In addition, chromatin immunoprecipitation analysis demonstrated that both tunicamycin treatment and ATF3 overexpression inhibited the recruitment of p300 to PDX-1 on the insulin promoter in MIN6N8 cells. |
| 4140 | 21986529 | Taken together, these results suggest that ATF3 inhibits PDX-1-mediated transactivation through the inhibition of p300-stimulated coactivation, which may lead to β-cell dysfunction by ER stress. |
| 4141 | 21986529 | ATF3 inhibits PDX-1-stimulated transactivation. |
| 4142 | 21986529 | Chronic endoplasmic reticulum (ER) stress leads to β-cell failure via reduction of pancreatic and duodenal homeobox-1 (PDX-1) activity, which contributes to the pathogenesis of type 2 diabetes. |
| 4143 | 21986529 | Previously, we showed that ATF3 downregulates PDX-1 gene expression in MIN6N8 pancreatic β-cells. |
| 4144 | 21986529 | Here, we investigated another role of ATF3 on the regulation of PDX-1 activity. |
| 4145 | 21986529 | ATF3 significantly inhibited PDX-1-stimulated transactivation of reporter plasmid containing promoters for PDX-1 binding element and the PDX-1 target gene glucokinase, which is dependent on C-terminal domain of ATF3. |
| 4146 | 21986529 | ATF3 interacted with PDX-1, and effectively inhibited p300-mediated transcriptional coactivation of the PBE-containing promoter, whereas C-terminal domain-deleted ATF3 did not inhibit the transcoactivation of p300. |
| 4147 | 21986529 | ATF3 decreased the interaction of p300 with PDX-1 in MIN6N8 cells coexpressing PDX-1 and ATF3. |
| 4148 | 21986529 | In addition, chromatin immunoprecipitation analysis demonstrated that both tunicamycin treatment and ATF3 overexpression inhibited the recruitment of p300 to PDX-1 on the insulin promoter in MIN6N8 cells. |
| 4149 | 21986529 | Taken together, these results suggest that ATF3 inhibits PDX-1-mediated transactivation through the inhibition of p300-stimulated coactivation, which may lead to β-cell dysfunction by ER stress. |
| 4150 | 21986529 | ATF3 inhibits PDX-1-stimulated transactivation. |
| 4151 | 21986529 | Chronic endoplasmic reticulum (ER) stress leads to β-cell failure via reduction of pancreatic and duodenal homeobox-1 (PDX-1) activity, which contributes to the pathogenesis of type 2 diabetes. |
| 4152 | 21986529 | Previously, we showed that ATF3 downregulates PDX-1 gene expression in MIN6N8 pancreatic β-cells. |
| 4153 | 21986529 | Here, we investigated another role of ATF3 on the regulation of PDX-1 activity. |
| 4154 | 21986529 | ATF3 significantly inhibited PDX-1-stimulated transactivation of reporter plasmid containing promoters for PDX-1 binding element and the PDX-1 target gene glucokinase, which is dependent on C-terminal domain of ATF3. |
| 4155 | 21986529 | ATF3 interacted with PDX-1, and effectively inhibited p300-mediated transcriptional coactivation of the PBE-containing promoter, whereas C-terminal domain-deleted ATF3 did not inhibit the transcoactivation of p300. |
| 4156 | 21986529 | ATF3 decreased the interaction of p300 with PDX-1 in MIN6N8 cells coexpressing PDX-1 and ATF3. |
| 4157 | 21986529 | In addition, chromatin immunoprecipitation analysis demonstrated that both tunicamycin treatment and ATF3 overexpression inhibited the recruitment of p300 to PDX-1 on the insulin promoter in MIN6N8 cells. |
| 4158 | 21986529 | Taken together, these results suggest that ATF3 inhibits PDX-1-mediated transactivation through the inhibition of p300-stimulated coactivation, which may lead to β-cell dysfunction by ER stress. |
| 4159 | 21986529 | ATF3 inhibits PDX-1-stimulated transactivation. |
| 4160 | 21986529 | Chronic endoplasmic reticulum (ER) stress leads to β-cell failure via reduction of pancreatic and duodenal homeobox-1 (PDX-1) activity, which contributes to the pathogenesis of type 2 diabetes. |
| 4161 | 21986529 | Previously, we showed that ATF3 downregulates PDX-1 gene expression in MIN6N8 pancreatic β-cells. |
| 4162 | 21986529 | Here, we investigated another role of ATF3 on the regulation of PDX-1 activity. |
| 4163 | 21986529 | ATF3 significantly inhibited PDX-1-stimulated transactivation of reporter plasmid containing promoters for PDX-1 binding element and the PDX-1 target gene glucokinase, which is dependent on C-terminal domain of ATF3. |
| 4164 | 21986529 | ATF3 interacted with PDX-1, and effectively inhibited p300-mediated transcriptional coactivation of the PBE-containing promoter, whereas C-terminal domain-deleted ATF3 did not inhibit the transcoactivation of p300. |
| 4165 | 21986529 | ATF3 decreased the interaction of p300 with PDX-1 in MIN6N8 cells coexpressing PDX-1 and ATF3. |
| 4166 | 21986529 | In addition, chromatin immunoprecipitation analysis demonstrated that both tunicamycin treatment and ATF3 overexpression inhibited the recruitment of p300 to PDX-1 on the insulin promoter in MIN6N8 cells. |
| 4167 | 21986529 | Taken together, these results suggest that ATF3 inhibits PDX-1-mediated transactivation through the inhibition of p300-stimulated coactivation, which may lead to β-cell dysfunction by ER stress. |
| 4168 | 21986529 | ATF3 inhibits PDX-1-stimulated transactivation. |
| 4169 | 21986529 | Chronic endoplasmic reticulum (ER) stress leads to β-cell failure via reduction of pancreatic and duodenal homeobox-1 (PDX-1) activity, which contributes to the pathogenesis of type 2 diabetes. |
| 4170 | 21986529 | Previously, we showed that ATF3 downregulates PDX-1 gene expression in MIN6N8 pancreatic β-cells. |
| 4171 | 21986529 | Here, we investigated another role of ATF3 on the regulation of PDX-1 activity. |
| 4172 | 21986529 | ATF3 significantly inhibited PDX-1-stimulated transactivation of reporter plasmid containing promoters for PDX-1 binding element and the PDX-1 target gene glucokinase, which is dependent on C-terminal domain of ATF3. |
| 4173 | 21986529 | ATF3 interacted with PDX-1, and effectively inhibited p300-mediated transcriptional coactivation of the PBE-containing promoter, whereas C-terminal domain-deleted ATF3 did not inhibit the transcoactivation of p300. |
| 4174 | 21986529 | ATF3 decreased the interaction of p300 with PDX-1 in MIN6N8 cells coexpressing PDX-1 and ATF3. |
| 4175 | 21986529 | In addition, chromatin immunoprecipitation analysis demonstrated that both tunicamycin treatment and ATF3 overexpression inhibited the recruitment of p300 to PDX-1 on the insulin promoter in MIN6N8 cells. |
| 4176 | 21986529 | Taken together, these results suggest that ATF3 inhibits PDX-1-mediated transactivation through the inhibition of p300-stimulated coactivation, which may lead to β-cell dysfunction by ER stress. |
| 4177 | 21986529 | ATF3 inhibits PDX-1-stimulated transactivation. |
| 4178 | 21986529 | Chronic endoplasmic reticulum (ER) stress leads to β-cell failure via reduction of pancreatic and duodenal homeobox-1 (PDX-1) activity, which contributes to the pathogenesis of type 2 diabetes. |
| 4179 | 21986529 | Previously, we showed that ATF3 downregulates PDX-1 gene expression in MIN6N8 pancreatic β-cells. |
| 4180 | 21986529 | Here, we investigated another role of ATF3 on the regulation of PDX-1 activity. |
| 4181 | 21986529 | ATF3 significantly inhibited PDX-1-stimulated transactivation of reporter plasmid containing promoters for PDX-1 binding element and the PDX-1 target gene glucokinase, which is dependent on C-terminal domain of ATF3. |
| 4182 | 21986529 | ATF3 interacted with PDX-1, and effectively inhibited p300-mediated transcriptional coactivation of the PBE-containing promoter, whereas C-terminal domain-deleted ATF3 did not inhibit the transcoactivation of p300. |
| 4183 | 21986529 | ATF3 decreased the interaction of p300 with PDX-1 in MIN6N8 cells coexpressing PDX-1 and ATF3. |
| 4184 | 21986529 | In addition, chromatin immunoprecipitation analysis demonstrated that both tunicamycin treatment and ATF3 overexpression inhibited the recruitment of p300 to PDX-1 on the insulin promoter in MIN6N8 cells. |
| 4185 | 21986529 | Taken together, these results suggest that ATF3 inhibits PDX-1-mediated transactivation through the inhibition of p300-stimulated coactivation, which may lead to β-cell dysfunction by ER stress. |
| 4186 | 21986529 | ATF3 inhibits PDX-1-stimulated transactivation. |
| 4187 | 21986529 | Chronic endoplasmic reticulum (ER) stress leads to β-cell failure via reduction of pancreatic and duodenal homeobox-1 (PDX-1) activity, which contributes to the pathogenesis of type 2 diabetes. |
| 4188 | 21986529 | Previously, we showed that ATF3 downregulates PDX-1 gene expression in MIN6N8 pancreatic β-cells. |
| 4189 | 21986529 | Here, we investigated another role of ATF3 on the regulation of PDX-1 activity. |
| 4190 | 21986529 | ATF3 significantly inhibited PDX-1-stimulated transactivation of reporter plasmid containing promoters for PDX-1 binding element and the PDX-1 target gene glucokinase, which is dependent on C-terminal domain of ATF3. |
| 4191 | 21986529 | ATF3 interacted with PDX-1, and effectively inhibited p300-mediated transcriptional coactivation of the PBE-containing promoter, whereas C-terminal domain-deleted ATF3 did not inhibit the transcoactivation of p300. |
| 4192 | 21986529 | ATF3 decreased the interaction of p300 with PDX-1 in MIN6N8 cells coexpressing PDX-1 and ATF3. |
| 4193 | 21986529 | In addition, chromatin immunoprecipitation analysis demonstrated that both tunicamycin treatment and ATF3 overexpression inhibited the recruitment of p300 to PDX-1 on the insulin promoter in MIN6N8 cells. |
| 4194 | 21986529 | Taken together, these results suggest that ATF3 inhibits PDX-1-mediated transactivation through the inhibition of p300-stimulated coactivation, which may lead to β-cell dysfunction by ER stress. |
| 4195 | 21986529 | ATF3 inhibits PDX-1-stimulated transactivation. |
| 4196 | 21986529 | Chronic endoplasmic reticulum (ER) stress leads to β-cell failure via reduction of pancreatic and duodenal homeobox-1 (PDX-1) activity, which contributes to the pathogenesis of type 2 diabetes. |
| 4197 | 21986529 | Previously, we showed that ATF3 downregulates PDX-1 gene expression in MIN6N8 pancreatic β-cells. |
| 4198 | 21986529 | Here, we investigated another role of ATF3 on the regulation of PDX-1 activity. |
| 4199 | 21986529 | ATF3 significantly inhibited PDX-1-stimulated transactivation of reporter plasmid containing promoters for PDX-1 binding element and the PDX-1 target gene glucokinase, which is dependent on C-terminal domain of ATF3. |
| 4200 | 21986529 | ATF3 interacted with PDX-1, and effectively inhibited p300-mediated transcriptional coactivation of the PBE-containing promoter, whereas C-terminal domain-deleted ATF3 did not inhibit the transcoactivation of p300. |
| 4201 | 21986529 | ATF3 decreased the interaction of p300 with PDX-1 in MIN6N8 cells coexpressing PDX-1 and ATF3. |
| 4202 | 21986529 | In addition, chromatin immunoprecipitation analysis demonstrated that both tunicamycin treatment and ATF3 overexpression inhibited the recruitment of p300 to PDX-1 on the insulin promoter in MIN6N8 cells. |
| 4203 | 21986529 | Taken together, these results suggest that ATF3 inhibits PDX-1-mediated transactivation through the inhibition of p300-stimulated coactivation, which may lead to β-cell dysfunction by ER stress. |
| 4204 | 22020533 | In stage 2, DMEM/F12 serum-free medium with ITS mix (insulin, transferrin, and selenite) is used to induce differentiation of hLMDFs into endoderm-like cells, as determined by the expression of the endoderm markers Sox17, Foxa2, and PDX1 (stage 2: mesenchymal-endoderm transition). |
| 4205 | 22028710 | Cyclin-Dependent Kinase 5/p35/p39: A Novel and Imminent Therapeutic Target for Diabetes Mellitus. |
| 4206 | 22028710 | Present therapies to minify hyperglycaemia and insulin resistance mainly target ATP-sensitive K(+) channels (K(ATP)) of pancreatic cells and PPAR-γ to enhance the insulin secretion and potential for GLUT expression, respectively. |
| 4207 | 22028710 | CDK5 is a serine/threonine protein kinase, which forms active complexes with p35 or p39 found principally in neurons and in pancreatic β cells. |
| 4208 | 22028710 | Pieces of evidence from recent studies recommend the vital role of CDK5 in physiological functions in nonneuronal cells such as glucose-stimulated insulin secretion in pancreatic cells. |
| 4209 | 22028710 | Inhibition of CDK5 averts the decrease of insulin gene expression through the inhibition of nuclear translocation of PDX-1 which is a transcription factor for the insulin gene. |
| 4210 | 22028710 | The present pieces of evidence designate that CDK5 might be a potential drug target for the regulation of glucose-stimulated insulin secretion in the treatment of diabetes mellitus. |
| 4211 | 22064706 | Therefore, the aim of this study was to explore MIF expression in vivo during development of obesity and insulin resistance in high-fat diet (HFD)-fed C57BL/6 mice and whether MIF inhibition could affect β-cell apoptosis and dysfunction induced by palmitic acid (PA) in vitro. |
| 4212 | 22064706 | Indeed, increase in systemic and locally produced MIF correlated well with the weight gain, triglyceride upregulation, glucose intolerance and insulin resistance, which developed in HFD-fed mice. |
| 4213 | 22064706 | Further, MIF inhibition conveyed a significant resistance to PA-induced downregulation of insulin and PDX-1 expression and ATP content. |
| 4214 | 22150363 | Reprogramming of pancreatic exocrine cells towards a beta (β) cell character using Pdx1, Ngn3 and MafA. |
| 4215 | 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. |
| 4216 | 22150363 | We constructed a new adenoviral vector encoding all three genes, called Ad-PNM (adenoviral Pdx1, Ngn3, MafA construct). |
| 4217 | 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. |
| 4218 | 22150363 | Reprogramming of pancreatic exocrine cells towards a beta (β) cell character using Pdx1, Ngn3 and MafA. |
| 4219 | 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. |
| 4220 | 22150363 | We constructed a new adenoviral vector encoding all three genes, called Ad-PNM (adenoviral Pdx1, Ngn3, MafA construct). |
| 4221 | 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. |
| 4222 | 22150363 | Reprogramming of pancreatic exocrine cells towards a beta (β) cell character using Pdx1, Ngn3 and MafA. |
| 4223 | 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. |
| 4224 | 22150363 | We constructed a new adenoviral vector encoding all three genes, called Ad-PNM (adenoviral Pdx1, Ngn3, MafA construct). |
| 4225 | 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. |
| 4226 | 22150363 | Reprogramming of pancreatic exocrine cells towards a beta (β) cell character using Pdx1, Ngn3 and MafA. |
| 4227 | 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. |
| 4228 | 22150363 | We constructed a new adenoviral vector encoding all three genes, called Ad-PNM (adenoviral Pdx1, Ngn3, MafA construct). |
| 4229 | 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. |
| 4230 | 22158542 | Rare mutations in PDX1 and PTF1A can cause pancreatic agenesis, however, most instances of this disorder are of unknown origin. |
| 4231 | 22215655 | We previously reported that forkhead box O1 (FoxO1) inhibits β-cell growth through a Pdx1-mediated mechanism. |
| 4232 | 22215655 | However, we also reported that FoxO1 protects against β-cell failure via the induction of NeuroD and MafA. |
| 4233 | 22215655 | Here, we investigate the physiological roles of FoxO1 in the pancreas by generating the mice with deletion of FoxO1 in the domains of the Pdx1 promoter (P-FoxO1-KO) or the insulin 2 promoter (β-FoxO1-KO) and analyzing the metabolic parameters and pancreatic morphology under two different conditions of increased metabolic demand: high-fat high-sucrose diet (HFHSD) and db/db background. |
| 4234 | 22215655 | Electron microscope analysis revealed fewer insulin granules in FoxO1 knockout db/db mice. |
| 4235 | 22215655 | We conclude that FoxO1 functions as a double-edged sword in the pancreas; FoxO1 essentially inhibits β-cell neogenesis from pancreatic duct cells but is required for the maintenance of insulin secretion under metabolic stress. |
| 4236 | 22215655 | We previously reported that forkhead box O1 (FoxO1) inhibits β-cell growth through a Pdx1-mediated mechanism. |
| 4237 | 22215655 | However, we also reported that FoxO1 protects against β-cell failure via the induction of NeuroD and MafA. |
| 4238 | 22215655 | Here, we investigate the physiological roles of FoxO1 in the pancreas by generating the mice with deletion of FoxO1 in the domains of the Pdx1 promoter (P-FoxO1-KO) or the insulin 2 promoter (β-FoxO1-KO) and analyzing the metabolic parameters and pancreatic morphology under two different conditions of increased metabolic demand: high-fat high-sucrose diet (HFHSD) and db/db background. |
| 4239 | 22215655 | Electron microscope analysis revealed fewer insulin granules in FoxO1 knockout db/db mice. |
| 4240 | 22215655 | We conclude that FoxO1 functions as a double-edged sword in the pancreas; FoxO1 essentially inhibits β-cell neogenesis from pancreatic duct cells but is required for the maintenance of insulin secretion under metabolic stress. |
| 4241 | 22249311 | A significant reduction in phosphorylated Akt was observed in the islets of c-Kit(Wv/+) mice (P<0.05) along with a decrease in phosphorylated Gsk3β (P<0.05), and cyclin D1 protein level (P<0.01) when compared with c-Kit(+/+) mice. |
| 4242 | 22249311 | However, c-Kit(Wv/+) mice that received 1-AKP treatment demonstrated normal fasting blood glucose with significantly improved glucose tolerance. 1-AKP-treated c-Kit(Wv/+) mice also showed increased β-catenin, cyclin D1 and Pdx-1 levels in islets, demonstrating that inhibition of Gsk3β activity led to increased β-cell proliferation and insulin secretion. |
| 4243 | 22249311 | These data suggest that c-Kit(Wv/+) male mice had alterations in the Akt/Gsk3β signaling pathway, which lead to β-cell dysfunction by decreasing Pdx-1 and cyclin D1 levels. |
| 4244 | 22249311 | A significant reduction in phosphorylated Akt was observed in the islets of c-Kit(Wv/+) mice (P<0.05) along with a decrease in phosphorylated Gsk3β (P<0.05), and cyclin D1 protein level (P<0.01) when compared with c-Kit(+/+) mice. |
| 4245 | 22249311 | However, c-Kit(Wv/+) mice that received 1-AKP treatment demonstrated normal fasting blood glucose with significantly improved glucose tolerance. 1-AKP-treated c-Kit(Wv/+) mice also showed increased β-catenin, cyclin D1 and Pdx-1 levels in islets, demonstrating that inhibition of Gsk3β activity led to increased β-cell proliferation and insulin secretion. |
| 4246 | 22249311 | These data suggest that c-Kit(Wv/+) male mice had alterations in the Akt/Gsk3β signaling pathway, which lead to β-cell dysfunction by decreasing Pdx-1 and cyclin D1 levels. |
| 4247 | 22253604 | An siRNA screen in pancreatic beta cells reveals a role for Gpr27 in insulin production. |
| 4248 | 22253604 | We show that knockdown of Gpr27 reduces endogenous mouse insulin promoter activity and glucose stimulated insulin secretion. |
| 4249 | 22253604 | Furthermore, we show that Pdx1 is important for Gpr27's effect on the insulin promoter and insulin secretion. |
| 4250 | 22253604 | Using this system, we identify Gpr27 as a positive regulator of insulin production. |
| 4251 | 22276854 | In particular, novel phosphorylation sites on proteins that mediate the pathology of type 2 diabetes, such as Pdx-1, Nkx.2, and Srebf1, will be valuable targets in ongoing phosphoproteomics studies. |
| 4252 | 22278131 | By day 15, we found up-regulation of a group of pancreatic progenitor marker genes including Pdx1, Ptf1a, Nkx6.1, Pax4 and Pax6. |
| 4253 | 22278131 | Most of these Pdx1(+) cells also expressed Nkx6.1. |
| 4254 | 22278131 | By day 15, we found up-regulation of a group of pancreatic progenitor marker genes including Pdx1, Ptf1a, Nkx6.1, Pax4 and Pax6. |
| 4255 | 22278131 | Most of these Pdx1(+) cells also expressed Nkx6.1. |
| 4256 | 22308370 | Glucose activates free fatty acid receptor 1 gene transcription via phosphatidylinositol-3-kinase-dependent O-GlcNAcylation of pancreas-duodenum homeobox-1. |
| 4257 | 22308370 | The G protein-coupled free fatty acid receptor-1 (FFA1/GPR40) plays a major role in the regulation of insulin secretion by fatty acids. |
| 4258 | 22308370 | GPR40 is considered a potential therapeutic target to enhance insulin secretion in type 2 diabetes; however, its mode of regulation is essentially unknown. |
| 4259 | 22308370 | We observed that glucose stimulates GPR40 gene transcription in pancreatic β-cells via increased binding of pancreas-duodenum homeobox-1 (Pdx-1) to the A-box in the HR2 region of the GPR40 promoter. |
| 4260 | 22308370 | Mutation of the Pdx-1 binding site within the HR2 abolishes glucose activation of GPR40 promoter activity. |
| 4261 | 22308370 | The stimulation of GPR40 expression and Pdx-1 binding to the HR2 in response to glucose are mimicked by N-acetyl glucosamine, an intermediate of the hexosamine biosynthesis pathway, and involve PI3K-dependent O-GlcNAcylation of Pdx-1 in the nucleus. |
| 4262 | 22308370 | We demonstrate that O-GlcNAc transferase (OGT) interacts with the product of the PI3K reaction, phosphatidylinositol 3,4,5-trisphosphate (PIP(3)), in the nucleus. |
| 4263 | 22308370 | This interaction enables OGT to catalyze O-GlcNAcylation of nuclear proteins, including Pdx-1. |
| 4264 | 22308370 | We conclude that glucose stimulates GPR40 gene expression at the transcriptional level through Pdx-1 binding to the HR2 region and via a signaling cascade that involves an interaction between OGT and PIP(3) at the nuclear membrane. |
| 4265 | 22308370 | Glucose activates free fatty acid receptor 1 gene transcription via phosphatidylinositol-3-kinase-dependent O-GlcNAcylation of pancreas-duodenum homeobox-1. |
| 4266 | 22308370 | The G protein-coupled free fatty acid receptor-1 (FFA1/GPR40) plays a major role in the regulation of insulin secretion by fatty acids. |
| 4267 | 22308370 | GPR40 is considered a potential therapeutic target to enhance insulin secretion in type 2 diabetes; however, its mode of regulation is essentially unknown. |
| 4268 | 22308370 | We observed that glucose stimulates GPR40 gene transcription in pancreatic β-cells via increased binding of pancreas-duodenum homeobox-1 (Pdx-1) to the A-box in the HR2 region of the GPR40 promoter. |
| 4269 | 22308370 | Mutation of the Pdx-1 binding site within the HR2 abolishes glucose activation of GPR40 promoter activity. |
| 4270 | 22308370 | The stimulation of GPR40 expression and Pdx-1 binding to the HR2 in response to glucose are mimicked by N-acetyl glucosamine, an intermediate of the hexosamine biosynthesis pathway, and involve PI3K-dependent O-GlcNAcylation of Pdx-1 in the nucleus. |
| 4271 | 22308370 | We demonstrate that O-GlcNAc transferase (OGT) interacts with the product of the PI3K reaction, phosphatidylinositol 3,4,5-trisphosphate (PIP(3)), in the nucleus. |
| 4272 | 22308370 | This interaction enables OGT to catalyze O-GlcNAcylation of nuclear proteins, including Pdx-1. |
| 4273 | 22308370 | We conclude that glucose stimulates GPR40 gene expression at the transcriptional level through Pdx-1 binding to the HR2 region and via a signaling cascade that involves an interaction between OGT and PIP(3) at the nuclear membrane. |
| 4274 | 22308370 | Glucose activates free fatty acid receptor 1 gene transcription via phosphatidylinositol-3-kinase-dependent O-GlcNAcylation of pancreas-duodenum homeobox-1. |
| 4275 | 22308370 | The G protein-coupled free fatty acid receptor-1 (FFA1/GPR40) plays a major role in the regulation of insulin secretion by fatty acids. |
| 4276 | 22308370 | GPR40 is considered a potential therapeutic target to enhance insulin secretion in type 2 diabetes; however, its mode of regulation is essentially unknown. |
| 4277 | 22308370 | We observed that glucose stimulates GPR40 gene transcription in pancreatic β-cells via increased binding of pancreas-duodenum homeobox-1 (Pdx-1) to the A-box in the HR2 region of the GPR40 promoter. |
| 4278 | 22308370 | Mutation of the Pdx-1 binding site within the HR2 abolishes glucose activation of GPR40 promoter activity. |
| 4279 | 22308370 | The stimulation of GPR40 expression and Pdx-1 binding to the HR2 in response to glucose are mimicked by N-acetyl glucosamine, an intermediate of the hexosamine biosynthesis pathway, and involve PI3K-dependent O-GlcNAcylation of Pdx-1 in the nucleus. |
| 4280 | 22308370 | We demonstrate that O-GlcNAc transferase (OGT) interacts with the product of the PI3K reaction, phosphatidylinositol 3,4,5-trisphosphate (PIP(3)), in the nucleus. |
| 4281 | 22308370 | This interaction enables OGT to catalyze O-GlcNAcylation of nuclear proteins, including Pdx-1. |
| 4282 | 22308370 | We conclude that glucose stimulates GPR40 gene expression at the transcriptional level through Pdx-1 binding to the HR2 region and via a signaling cascade that involves an interaction between OGT and PIP(3) at the nuclear membrane. |
| 4283 | 22308370 | Glucose activates free fatty acid receptor 1 gene transcription via phosphatidylinositol-3-kinase-dependent O-GlcNAcylation of pancreas-duodenum homeobox-1. |
| 4284 | 22308370 | The G protein-coupled free fatty acid receptor-1 (FFA1/GPR40) plays a major role in the regulation of insulin secretion by fatty acids. |
| 4285 | 22308370 | GPR40 is considered a potential therapeutic target to enhance insulin secretion in type 2 diabetes; however, its mode of regulation is essentially unknown. |
| 4286 | 22308370 | We observed that glucose stimulates GPR40 gene transcription in pancreatic β-cells via increased binding of pancreas-duodenum homeobox-1 (Pdx-1) to the A-box in the HR2 region of the GPR40 promoter. |
| 4287 | 22308370 | Mutation of the Pdx-1 binding site within the HR2 abolishes glucose activation of GPR40 promoter activity. |
| 4288 | 22308370 | The stimulation of GPR40 expression and Pdx-1 binding to the HR2 in response to glucose are mimicked by N-acetyl glucosamine, an intermediate of the hexosamine biosynthesis pathway, and involve PI3K-dependent O-GlcNAcylation of Pdx-1 in the nucleus. |
| 4289 | 22308370 | We demonstrate that O-GlcNAc transferase (OGT) interacts with the product of the PI3K reaction, phosphatidylinositol 3,4,5-trisphosphate (PIP(3)), in the nucleus. |
| 4290 | 22308370 | This interaction enables OGT to catalyze O-GlcNAcylation of nuclear proteins, including Pdx-1. |
| 4291 | 22308370 | We conclude that glucose stimulates GPR40 gene expression at the transcriptional level through Pdx-1 binding to the HR2 region and via a signaling cascade that involves an interaction between OGT and PIP(3) at the nuclear membrane. |
| 4292 | 22308370 | Glucose activates free fatty acid receptor 1 gene transcription via phosphatidylinositol-3-kinase-dependent O-GlcNAcylation of pancreas-duodenum homeobox-1. |
| 4293 | 22308370 | The G protein-coupled free fatty acid receptor-1 (FFA1/GPR40) plays a major role in the regulation of insulin secretion by fatty acids. |
| 4294 | 22308370 | GPR40 is considered a potential therapeutic target to enhance insulin secretion in type 2 diabetes; however, its mode of regulation is essentially unknown. |
| 4295 | 22308370 | We observed that glucose stimulates GPR40 gene transcription in pancreatic β-cells via increased binding of pancreas-duodenum homeobox-1 (Pdx-1) to the A-box in the HR2 region of the GPR40 promoter. |
| 4296 | 22308370 | Mutation of the Pdx-1 binding site within the HR2 abolishes glucose activation of GPR40 promoter activity. |
| 4297 | 22308370 | The stimulation of GPR40 expression and Pdx-1 binding to the HR2 in response to glucose are mimicked by N-acetyl glucosamine, an intermediate of the hexosamine biosynthesis pathway, and involve PI3K-dependent O-GlcNAcylation of Pdx-1 in the nucleus. |
| 4298 | 22308370 | We demonstrate that O-GlcNAc transferase (OGT) interacts with the product of the PI3K reaction, phosphatidylinositol 3,4,5-trisphosphate (PIP(3)), in the nucleus. |
| 4299 | 22308370 | This interaction enables OGT to catalyze O-GlcNAcylation of nuclear proteins, including Pdx-1. |
| 4300 | 22308370 | We conclude that glucose stimulates GPR40 gene expression at the transcriptional level through Pdx-1 binding to the HR2 region and via a signaling cascade that involves an interaction between OGT and PIP(3) at the nuclear membrane. |
| 4301 | 22310720 | Pancreatic specific genes were turned on, such as transcription factors (Pdx-1, Ngn3 and Nkx6.1), genes related to endocrine function (Glut-2 and PC2) or β cell function (Kir6.2, SUR1). |
| 4302 | 22383081 | Although the role of transcription factors (Pdx-1, MafA, NeuroD) on β-cell functions is understood, alterations in internal milieu of pancreatic tissue that affects β-cell functions in CP has not been elucidated. |
| 4303 | 22384192 | TG mice had impaired glucose tolerance and some of them indeed developed diabetes due to the reduction of β cell mass, which is associated with decreased Pdx1 and MafA in β cells. |
| 4304 | 22393165 | Further studies on the expression of cyclin D1, cyclin D2 and Cdk4 demonstrated that these genes were significantly up-regulated in the ABL-treated mice. |
| 4305 | 22393165 | Moreover, the expression of PDX-1 (pancreatic and duodenal homeobox 1), Ngn3 (neurogenin 3), insulin, GLUT-1 (glucose transporter 1) and glucokinase was also increased in the ABL-treated mice. |
| 4306 | 22393382 | Interestingly, they maintained expression of β-cell specific markers, such as PDX1, NKX6.1, GLUT2 and insulin. |
| 4307 | 22393382 | Gene expression analysis showed that β-TC3R cells were characterized by downregulation of IL-1β and IFN-γ receptors and upregulation of SOCS3, the classical negative regulator of cytokines signaling. |
| 4308 | 22393382 | Among them, SUMO4, a negative feedback regulator in NF-kB and JAK/STAT signaling pathways, resulted hyper-expressed. |
| 4309 | 22393382 | Silencing of SUMO4 was able to restore sensitivity to cytokine-induced cell death in β-TC3R cells, suggesting it may play a key role in acquired cytokine resistance by blocking JAK/STAT and NF-kB lethal signaling.In conclusion, our study represents the first extensive proteomic characterization of a murine cytokine-resistant β-cell line, which might represent a useful tool for studying the mechanisms involved in resistance to cytokine-mediated β-cell death. |
| 4310 | 22403172 | Through candidate gene approach, we confirmed that Pax6 controls the mRNA levels of the insulin 1 and 2, Pdx1, MafA, GLUT2, and PC1/3 genes in β-cells. |
| 4311 | 22403172 | Importantly, we identified new Pax6 target genes coding for GK, Nkx6.1, cMaf, PC2, GLP-1R and GIPR which are all involved in β-cell function. |
| 4312 | 22436693 | Compared with CC, pre- and postnatal LP (RR) decreased β-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Isl1, Rfx6, and Slc2a2 mRNA levels. |
| 4313 | 22436693 | LP only in pregnancy (RC) also decreased β-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Rfx6, and Ins mRNA levels. |
| 4314 | 22436693 | Postnatal LP offspring (CR) showed decreased β-cell mass but increased β-cell fraction, aggregate number, and Hnf1a, Hnf4a, Rfx6, and Slc2a2 mRNA levels. |
| 4315 | 22436693 | Compared with CC, pre- and postnatal LP (RR) decreased β-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Isl1, Rfx6, and Slc2a2 mRNA levels. |
| 4316 | 22436693 | LP only in pregnancy (RC) also decreased β-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Rfx6, and Ins mRNA levels. |
| 4317 | 22436693 | Postnatal LP offspring (CR) showed decreased β-cell mass but increased β-cell fraction, aggregate number, and Hnf1a, Hnf4a, Rfx6, and Slc2a2 mRNA levels. |
| 4318 | 22465129 | Here, we report that rat bmMSCs were converted in vitro into insulin-producing cells by suppressing two-repressor genes repressor element-1 silencing transcription factor/neuronal restrictive silencing factor (Rest/Nrsf) and sonic hedgehog (Shh) and by over-expressing pancreas and duodenal transcription factor 1 (Pdx1). |
| 4319 | 22488273 | Regulation of mesenchymal stem cell differentiation and insulin secretion by differential expression of Pdx-1. |
| 4320 | 22488273 | Our previous work has also demonstrated the feasibility of inducing mesenchymal stem cells (MSC) to insulin secreting cells through overexpression of Pdx-1, a pancreas and islet-specific transcription factor that plays a major role in differentiation of islet β-cells during development (Yuan et al. in Mol Biol Rep 37:4023-4031, 2010). |
| 4321 | 22488273 | The purpose of this study is to address the issue whether the insulin secretion level from the differentiated MSC lines are determined by the expression level of the Pdx-1 transgene. |
| 4322 | 22488273 | Using RT-PCR analysis and insulin secretion assay, we have analyzed Pdx-1 mRNA levels and insulin secretion from these stable MSC lines. |
| 4323 | 22488273 | Our results showed that Pdx-1 expression is absolutely required for the differentiation of MSC lines to insulin secreting cell lines. |
| 4324 | 22488273 | Furthermore, we demonstrated that the level of Pdx-1 expression is closely correlated with level of insulin mRNA and insulin secretion level in differentiated MSC stable cell lines. |
| 4325 | 22488273 | These findings suggest that the level of Pdx-1 expression plays a key role in induction of MSCs to insulin secreting cells. |
| 4326 | 22488273 | Regulation of mesenchymal stem cell differentiation and insulin secretion by differential expression of Pdx-1. |
| 4327 | 22488273 | Our previous work has also demonstrated the feasibility of inducing mesenchymal stem cells (MSC) to insulin secreting cells through overexpression of Pdx-1, a pancreas and islet-specific transcription factor that plays a major role in differentiation of islet β-cells during development (Yuan et al. in Mol Biol Rep 37:4023-4031, 2010). |
| 4328 | 22488273 | The purpose of this study is to address the issue whether the insulin secretion level from the differentiated MSC lines are determined by the expression level of the Pdx-1 transgene. |
| 4329 | 22488273 | Using RT-PCR analysis and insulin secretion assay, we have analyzed Pdx-1 mRNA levels and insulin secretion from these stable MSC lines. |
| 4330 | 22488273 | Our results showed that Pdx-1 expression is absolutely required for the differentiation of MSC lines to insulin secreting cell lines. |
| 4331 | 22488273 | Furthermore, we demonstrated that the level of Pdx-1 expression is closely correlated with level of insulin mRNA and insulin secretion level in differentiated MSC stable cell lines. |
| 4332 | 22488273 | These findings suggest that the level of Pdx-1 expression plays a key role in induction of MSCs to insulin secreting cells. |
| 4333 | 22488273 | Regulation of mesenchymal stem cell differentiation and insulin secretion by differential expression of Pdx-1. |
| 4334 | 22488273 | Our previous work has also demonstrated the feasibility of inducing mesenchymal stem cells (MSC) to insulin secreting cells through overexpression of Pdx-1, a pancreas and islet-specific transcription factor that plays a major role in differentiation of islet β-cells during development (Yuan et al. in Mol Biol Rep 37:4023-4031, 2010). |
| 4335 | 22488273 | The purpose of this study is to address the issue whether the insulin secretion level from the differentiated MSC lines are determined by the expression level of the Pdx-1 transgene. |
| 4336 | 22488273 | Using RT-PCR analysis and insulin secretion assay, we have analyzed Pdx-1 mRNA levels and insulin secretion from these stable MSC lines. |
| 4337 | 22488273 | Our results showed that Pdx-1 expression is absolutely required for the differentiation of MSC lines to insulin secreting cell lines. |
| 4338 | 22488273 | Furthermore, we demonstrated that the level of Pdx-1 expression is closely correlated with level of insulin mRNA and insulin secretion level in differentiated MSC stable cell lines. |
| 4339 | 22488273 | These findings suggest that the level of Pdx-1 expression plays a key role in induction of MSCs to insulin secreting cells. |
| 4340 | 22488273 | Regulation of mesenchymal stem cell differentiation and insulin secretion by differential expression of Pdx-1. |
| 4341 | 22488273 | Our previous work has also demonstrated the feasibility of inducing mesenchymal stem cells (MSC) to insulin secreting cells through overexpression of Pdx-1, a pancreas and islet-specific transcription factor that plays a major role in differentiation of islet β-cells during development (Yuan et al. in Mol Biol Rep 37:4023-4031, 2010). |
| 4342 | 22488273 | The purpose of this study is to address the issue whether the insulin secretion level from the differentiated MSC lines are determined by the expression level of the Pdx-1 transgene. |
| 4343 | 22488273 | Using RT-PCR analysis and insulin secretion assay, we have analyzed Pdx-1 mRNA levels and insulin secretion from these stable MSC lines. |
| 4344 | 22488273 | Our results showed that Pdx-1 expression is absolutely required for the differentiation of MSC lines to insulin secreting cell lines. |
| 4345 | 22488273 | Furthermore, we demonstrated that the level of Pdx-1 expression is closely correlated with level of insulin mRNA and insulin secretion level in differentiated MSC stable cell lines. |
| 4346 | 22488273 | These findings suggest that the level of Pdx-1 expression plays a key role in induction of MSCs to insulin secreting cells. |
| 4347 | 22488273 | Regulation of mesenchymal stem cell differentiation and insulin secretion by differential expression of Pdx-1. |
| 4348 | 22488273 | Our previous work has also demonstrated the feasibility of inducing mesenchymal stem cells (MSC) to insulin secreting cells through overexpression of Pdx-1, a pancreas and islet-specific transcription factor that plays a major role in differentiation of islet β-cells during development (Yuan et al. in Mol Biol Rep 37:4023-4031, 2010). |
| 4349 | 22488273 | The purpose of this study is to address the issue whether the insulin secretion level from the differentiated MSC lines are determined by the expression level of the Pdx-1 transgene. |
| 4350 | 22488273 | Using RT-PCR analysis and insulin secretion assay, we have analyzed Pdx-1 mRNA levels and insulin secretion from these stable MSC lines. |
| 4351 | 22488273 | Our results showed that Pdx-1 expression is absolutely required for the differentiation of MSC lines to insulin secreting cell lines. |
| 4352 | 22488273 | Furthermore, we demonstrated that the level of Pdx-1 expression is closely correlated with level of insulin mRNA and insulin secretion level in differentiated MSC stable cell lines. |
| 4353 | 22488273 | These findings suggest that the level of Pdx-1 expression plays a key role in induction of MSCs to insulin secreting cells. |
| 4354 | 22488273 | Regulation of mesenchymal stem cell differentiation and insulin secretion by differential expression of Pdx-1. |
| 4355 | 22488273 | Our previous work has also demonstrated the feasibility of inducing mesenchymal stem cells (MSC) to insulin secreting cells through overexpression of Pdx-1, a pancreas and islet-specific transcription factor that plays a major role in differentiation of islet β-cells during development (Yuan et al. in Mol Biol Rep 37:4023-4031, 2010). |
| 4356 | 22488273 | The purpose of this study is to address the issue whether the insulin secretion level from the differentiated MSC lines are determined by the expression level of the Pdx-1 transgene. |
| 4357 | 22488273 | Using RT-PCR analysis and insulin secretion assay, we have analyzed Pdx-1 mRNA levels and insulin secretion from these stable MSC lines. |
| 4358 | 22488273 | Our results showed that Pdx-1 expression is absolutely required for the differentiation of MSC lines to insulin secreting cell lines. |
| 4359 | 22488273 | Furthermore, we demonstrated that the level of Pdx-1 expression is closely correlated with level of insulin mRNA and insulin secretion level in differentiated MSC stable cell lines. |
| 4360 | 22488273 | These findings suggest that the level of Pdx-1 expression plays a key role in induction of MSCs to insulin secreting cells. |
| 4361 | 22488273 | Regulation of mesenchymal stem cell differentiation and insulin secretion by differential expression of Pdx-1. |
| 4362 | 22488273 | Our previous work has also demonstrated the feasibility of inducing mesenchymal stem cells (MSC) to insulin secreting cells through overexpression of Pdx-1, a pancreas and islet-specific transcription factor that plays a major role in differentiation of islet β-cells during development (Yuan et al. in Mol Biol Rep 37:4023-4031, 2010). |
| 4363 | 22488273 | The purpose of this study is to address the issue whether the insulin secretion level from the differentiated MSC lines are determined by the expression level of the Pdx-1 transgene. |
| 4364 | 22488273 | Using RT-PCR analysis and insulin secretion assay, we have analyzed Pdx-1 mRNA levels and insulin secretion from these stable MSC lines. |
| 4365 | 22488273 | Our results showed that Pdx-1 expression is absolutely required for the differentiation of MSC lines to insulin secreting cell lines. |
| 4366 | 22488273 | Furthermore, we demonstrated that the level of Pdx-1 expression is closely correlated with level of insulin mRNA and insulin secretion level in differentiated MSC stable cell lines. |
| 4367 | 22488273 | These findings suggest that the level of Pdx-1 expression plays a key role in induction of MSCs to insulin secreting cells. |
| 4368 | 22509401 | Mice that are haploinsufficient for Pdx1 display impaired glucose tolerance and lack the ability to increase beta cell mass in response to decreased insulin signaling. |
| 4369 | 22529013 | Recently it has been reported that PDX1-positive pancreatic progenitors, derived from human embryonic stem cells, express the surface marker CD24. |
| 4370 | 22529013 | Thus CD24 is not a suitable cell surface marker for identification of PDX1-positive progenitor cells. |
| 4371 | 22529013 | Recently it has been reported that PDX1-positive pancreatic progenitors, derived from human embryonic stem cells, express the surface marker CD24. |
| 4372 | 22529013 | Thus CD24 is not a suitable cell surface marker for identification of PDX1-positive progenitor cells. |
| 4373 | 22570331 | Mutations in pancreatic duodenal homeobox 1 (PDX-1) can cause a monogenic form of diabetes (maturity onset diabetes of the young 4) in humans, and silencing Pdx-1 in pancreatic β-cells of mice causes diabetes. |
| 4374 | 22570331 | PDX-1 expression was decreased in pancreatic islets from patients with T2D compared with nondiabetic donors (P = 0.0002) and correlated positively with insulin expression (rho = 0.59, P = 0.000001) and glucose-stimulated insulin secretion (rho = 0.41, P = 0.005) in the human islets. |
| 4375 | 22570331 | Our data further indicate that hyperglycemia decreases gene expression and increases DNA methylation of PDX-1 because glycosylated hemoglobin (HbA1c) correlates negatively with mRNA expression (rho = -0.50, P = 0.0004) and positively with DNA methylation (rho = 0.54, P = 0.00024) of PDX-1 in the human islets. |
| 4376 | 22570331 | Furthermore, while Pdx-1 expression decreased, Pdx-1 methylation and Dnmt1 expression increased in clonal β-cells exposed to high glucose. |
| 4377 | 22570331 | The expression levels of PDX-1 were further associated with insulin secretion in the human islets. |
| 4378 | 22570331 | Mutations in pancreatic duodenal homeobox 1 (PDX-1) can cause a monogenic form of diabetes (maturity onset diabetes of the young 4) in humans, and silencing Pdx-1 in pancreatic β-cells of mice causes diabetes. |
| 4379 | 22570331 | PDX-1 expression was decreased in pancreatic islets from patients with T2D compared with nondiabetic donors (P = 0.0002) and correlated positively with insulin expression (rho = 0.59, P = 0.000001) and glucose-stimulated insulin secretion (rho = 0.41, P = 0.005) in the human islets. |
| 4380 | 22570331 | Our data further indicate that hyperglycemia decreases gene expression and increases DNA methylation of PDX-1 because glycosylated hemoglobin (HbA1c) correlates negatively with mRNA expression (rho = -0.50, P = 0.0004) and positively with DNA methylation (rho = 0.54, P = 0.00024) of PDX-1 in the human islets. |
| 4381 | 22570331 | Furthermore, while Pdx-1 expression decreased, Pdx-1 methylation and Dnmt1 expression increased in clonal β-cells exposed to high glucose. |
| 4382 | 22570331 | The expression levels of PDX-1 were further associated with insulin secretion in the human islets. |
| 4383 | 22570331 | Mutations in pancreatic duodenal homeobox 1 (PDX-1) can cause a monogenic form of diabetes (maturity onset diabetes of the young 4) in humans, and silencing Pdx-1 in pancreatic β-cells of mice causes diabetes. |
| 4384 | 22570331 | PDX-1 expression was decreased in pancreatic islets from patients with T2D compared with nondiabetic donors (P = 0.0002) and correlated positively with insulin expression (rho = 0.59, P = 0.000001) and glucose-stimulated insulin secretion (rho = 0.41, P = 0.005) in the human islets. |
| 4385 | 22570331 | Our data further indicate that hyperglycemia decreases gene expression and increases DNA methylation of PDX-1 because glycosylated hemoglobin (HbA1c) correlates negatively with mRNA expression (rho = -0.50, P = 0.0004) and positively with DNA methylation (rho = 0.54, P = 0.00024) of PDX-1 in the human islets. |
| 4386 | 22570331 | Furthermore, while Pdx-1 expression decreased, Pdx-1 methylation and Dnmt1 expression increased in clonal β-cells exposed to high glucose. |
| 4387 | 22570331 | The expression levels of PDX-1 were further associated with insulin secretion in the human islets. |
| 4388 | 22570331 | Mutations in pancreatic duodenal homeobox 1 (PDX-1) can cause a monogenic form of diabetes (maturity onset diabetes of the young 4) in humans, and silencing Pdx-1 in pancreatic β-cells of mice causes diabetes. |
| 4389 | 22570331 | PDX-1 expression was decreased in pancreatic islets from patients with T2D compared with nondiabetic donors (P = 0.0002) and correlated positively with insulin expression (rho = 0.59, P = 0.000001) and glucose-stimulated insulin secretion (rho = 0.41, P = 0.005) in the human islets. |
| 4390 | 22570331 | Our data further indicate that hyperglycemia decreases gene expression and increases DNA methylation of PDX-1 because glycosylated hemoglobin (HbA1c) correlates negatively with mRNA expression (rho = -0.50, P = 0.0004) and positively with DNA methylation (rho = 0.54, P = 0.00024) of PDX-1 in the human islets. |
| 4391 | 22570331 | Furthermore, while Pdx-1 expression decreased, Pdx-1 methylation and Dnmt1 expression increased in clonal β-cells exposed to high glucose. |
| 4392 | 22570331 | The expression levels of PDX-1 were further associated with insulin secretion in the human islets. |
| 4393 | 22570331 | Mutations in pancreatic duodenal homeobox 1 (PDX-1) can cause a monogenic form of diabetes (maturity onset diabetes of the young 4) in humans, and silencing Pdx-1 in pancreatic β-cells of mice causes diabetes. |
| 4394 | 22570331 | PDX-1 expression was decreased in pancreatic islets from patients with T2D compared with nondiabetic donors (P = 0.0002) and correlated positively with insulin expression (rho = 0.59, P = 0.000001) and glucose-stimulated insulin secretion (rho = 0.41, P = 0.005) in the human islets. |
| 4395 | 22570331 | Our data further indicate that hyperglycemia decreases gene expression and increases DNA methylation of PDX-1 because glycosylated hemoglobin (HbA1c) correlates negatively with mRNA expression (rho = -0.50, P = 0.0004) and positively with DNA methylation (rho = 0.54, P = 0.00024) of PDX-1 in the human islets. |
| 4396 | 22570331 | Furthermore, while Pdx-1 expression decreased, Pdx-1 methylation and Dnmt1 expression increased in clonal β-cells exposed to high glucose. |
| 4397 | 22570331 | The expression levels of PDX-1 were further associated with insulin secretion in the human islets. |
| 4398 | 22586489 | Furthermore, Pdx1(+)/Insulin(-) cells were detected following STZ treatment, indicating the involvement of endocrine progenitor cells in the regeneration of these non-β cells. |
| 4399 | 22586489 | This is further confirmed by the detection of Pdx1(+)/glucagon(+) cells and Pdx1(+)/somatostatin(+) cells following STZ treatment. |
| 4400 | 22586489 | Furthermore, Pdx1(+)/Insulin(-) cells were detected following STZ treatment, indicating the involvement of endocrine progenitor cells in the regeneration of these non-β cells. |
| 4401 | 22586489 | This is further confirmed by the detection of Pdx1(+)/glucagon(+) cells and Pdx1(+)/somatostatin(+) cells following STZ treatment. |
| 4402 | 22620683 | Further study demonstrated that LA upregulated Pdx1 and Bcl2 gene expression, reduced Bax gene expression, and promoted phosphorylation of Akt in HIT-T15 cells treated with high glucose. |
| 4403 | 22620683 | However, inhibition of Akt by PI3K/AKT antagonist LY294002 only slightly reversed the anti-apoptosis effect of LA and mildly decreased the gene expression level of Pdx1 (P > 0.05). |
| 4404 | 22620683 | Further study demonstrated that LA upregulated Pdx1 and Bcl2 gene expression, reduced Bax gene expression, and promoted phosphorylation of Akt in HIT-T15 cells treated with high glucose. |
| 4405 | 22620683 | However, inhibition of Akt by PI3K/AKT antagonist LY294002 only slightly reversed the anti-apoptosis effect of LA and mildly decreased the gene expression level of Pdx1 (P > 0.05). |
| 4406 | 22644623 | Protective effect of rat pancreatic progenitors cells expressing Pdx1 and nestin on islets survival and function in vitro and in vivo. |
| 4407 | 22644623 | The aim of our research was to investigate the protective effect of rat pancreatic-duodenal homeobox 1 (Pdx1)(+)/nestin(+) PPCs on islets. |
| 4408 | 22644623 | In vitro, co-culturing islets with Pdx1(+)/nestin(+) PPCs prolonged the former survival from 7 to 14 days. |
| 4409 | 22644623 | In vivo, co-transplanting islets and Pdx1(+)/nestin(+) PPCs for 3 days, the blood glucose of diabetic rat was significantly decreased to normal level and sustained for 2 weeks. |
| 4410 | 22644623 | Without Pdx1(+)/nestin(+) PPCs in islets transplantation, hyperglycemia was reversed at day 7 and recovered at day 15. |
| 4411 | 22644623 | Our study showed that Pdx1(+)/nestin(+) PPCs displayed the ability of preserving islets viability and function in vitro and prolonging their survival in vivo. |
| 4412 | 22644623 | Protective effect of rat pancreatic progenitors cells expressing Pdx1 and nestin on islets survival and function in vitro and in vivo. |
| 4413 | 22644623 | The aim of our research was to investigate the protective effect of rat pancreatic-duodenal homeobox 1 (Pdx1)(+)/nestin(+) PPCs on islets. |
| 4414 | 22644623 | In vitro, co-culturing islets with Pdx1(+)/nestin(+) PPCs prolonged the former survival from 7 to 14 days. |
| 4415 | 22644623 | In vivo, co-transplanting islets and Pdx1(+)/nestin(+) PPCs for 3 days, the blood glucose of diabetic rat was significantly decreased to normal level and sustained for 2 weeks. |
| 4416 | 22644623 | Without Pdx1(+)/nestin(+) PPCs in islets transplantation, hyperglycemia was reversed at day 7 and recovered at day 15. |
| 4417 | 22644623 | Our study showed that Pdx1(+)/nestin(+) PPCs displayed the ability of preserving islets viability and function in vitro and prolonging their survival in vivo. |
| 4418 | 22644623 | Protective effect of rat pancreatic progenitors cells expressing Pdx1 and nestin on islets survival and function in vitro and in vivo. |
| 4419 | 22644623 | The aim of our research was to investigate the protective effect of rat pancreatic-duodenal homeobox 1 (Pdx1)(+)/nestin(+) PPCs on islets. |
| 4420 | 22644623 | In vitro, co-culturing islets with Pdx1(+)/nestin(+) PPCs prolonged the former survival from 7 to 14 days. |
| 4421 | 22644623 | In vivo, co-transplanting islets and Pdx1(+)/nestin(+) PPCs for 3 days, the blood glucose of diabetic rat was significantly decreased to normal level and sustained for 2 weeks. |
| 4422 | 22644623 | Without Pdx1(+)/nestin(+) PPCs in islets transplantation, hyperglycemia was reversed at day 7 and recovered at day 15. |
| 4423 | 22644623 | Our study showed that Pdx1(+)/nestin(+) PPCs displayed the ability of preserving islets viability and function in vitro and prolonging their survival in vivo. |
| 4424 | 22644623 | Protective effect of rat pancreatic progenitors cells expressing Pdx1 and nestin on islets survival and function in vitro and in vivo. |
| 4425 | 22644623 | The aim of our research was to investigate the protective effect of rat pancreatic-duodenal homeobox 1 (Pdx1)(+)/nestin(+) PPCs on islets. |
| 4426 | 22644623 | In vitro, co-culturing islets with Pdx1(+)/nestin(+) PPCs prolonged the former survival from 7 to 14 days. |
| 4427 | 22644623 | In vivo, co-transplanting islets and Pdx1(+)/nestin(+) PPCs for 3 days, the blood glucose of diabetic rat was significantly decreased to normal level and sustained for 2 weeks. |
| 4428 | 22644623 | Without Pdx1(+)/nestin(+) PPCs in islets transplantation, hyperglycemia was reversed at day 7 and recovered at day 15. |
| 4429 | 22644623 | Our study showed that Pdx1(+)/nestin(+) PPCs displayed the ability of preserving islets viability and function in vitro and prolonging their survival in vivo. |
| 4430 | 22644623 | Protective effect of rat pancreatic progenitors cells expressing Pdx1 and nestin on islets survival and function in vitro and in vivo. |
| 4431 | 22644623 | The aim of our research was to investigate the protective effect of rat pancreatic-duodenal homeobox 1 (Pdx1)(+)/nestin(+) PPCs on islets. |
| 4432 | 22644623 | In vitro, co-culturing islets with Pdx1(+)/nestin(+) PPCs prolonged the former survival from 7 to 14 days. |
| 4433 | 22644623 | In vivo, co-transplanting islets and Pdx1(+)/nestin(+) PPCs for 3 days, the blood glucose of diabetic rat was significantly decreased to normal level and sustained for 2 weeks. |
| 4434 | 22644623 | Without Pdx1(+)/nestin(+) PPCs in islets transplantation, hyperglycemia was reversed at day 7 and recovered at day 15. |
| 4435 | 22644623 | Our study showed that Pdx1(+)/nestin(+) PPCs displayed the ability of preserving islets viability and function in vitro and prolonging their survival in vivo. |
| 4436 | 22644623 | Protective effect of rat pancreatic progenitors cells expressing Pdx1 and nestin on islets survival and function in vitro and in vivo. |
| 4437 | 22644623 | The aim of our research was to investigate the protective effect of rat pancreatic-duodenal homeobox 1 (Pdx1)(+)/nestin(+) PPCs on islets. |
| 4438 | 22644623 | In vitro, co-culturing islets with Pdx1(+)/nestin(+) PPCs prolonged the former survival from 7 to 14 days. |
| 4439 | 22644623 | In vivo, co-transplanting islets and Pdx1(+)/nestin(+) PPCs for 3 days, the blood glucose of diabetic rat was significantly decreased to normal level and sustained for 2 weeks. |
| 4440 | 22644623 | Without Pdx1(+)/nestin(+) PPCs in islets transplantation, hyperglycemia was reversed at day 7 and recovered at day 15. |
| 4441 | 22644623 | Our study showed that Pdx1(+)/nestin(+) PPCs displayed the ability of preserving islets viability and function in vitro and prolonging their survival in vivo. |
| 4442 | 22652787 | Hepatic oval cells can be redirected to the beta-cell linage by an appropriate combination of high extracellular glucose, specific extracellular matrix proteins (laminin and fibronectin), cytokines (activin A), and the expression of several differentiation-related transcription factors (Pdx-1, Ngn-3, MafA). |
| 4443 | 22669248 | Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice. |
| 4444 | 22669248 | The orexigenic hormone ghrelin is important in diabetes because it has an inhibitory effect on insulin secretion. |
| 4445 | 22669248 | Ghrelin ablation in leptin-deficient ob/ob (Ghrelin(-/-):ob/ob) mice increases insulin secretion and improves hyperglycemia. |
| 4446 | 22669248 | The physiologically relevant ghrelin receptor is the growth hormone secretagogue receptor (GHS-R), and GHS-R antagonists are thought to be an effective strategy for treating diabetes. |
| 4447 | 22669248 | However, since some of ghrelin's effects are independent of GHS-R, we have utilized genetic approaches to determine whether ghrelin's effect on insulin secretion is mediated through GHS-R and whether GHS-R antagonism indeed inhibits insulin secretion. |
| 4448 | 22669248 | Ghsr ablation did not rescue the hyperphagia, obesity, or insulin resistance of ob/ob mice. |
| 4449 | 22669248 | Surprisingly, Ghsr ablation worsened the hyperglycemia, decreased insulin, and impaired glucose tolerance. |
| 4450 | 22669248 | Consistently, Ghsr ablation in ob/ob mice upregulated negative β-cell regulators (such as UCP-2, SREBP-1c, ChREBP, and MIF-1) and downregulated positive β-cell regulators (such as HIF-1α, FGF-21, and PDX-1) in whole pancreas; this suggests that Ghsr ablation impairs pancreatic β-cell function in leptin deficiency. |
| 4451 | 22669248 | In summary, because Ghsr ablation in leptin deficiency impairs insulin secretion and worsens hyperglycemia, this suggests that GHS-R antagonists may actually aggravate diabetes under certain conditions. |
| 4452 | 22669248 | The paradoxical effects of ghrelin ablation and Ghsr ablation in ob/ob mice highlight the complexity of the ghrelin-signaling pathway. |
| 4453 | 22685335 | We used the hydrodynamic approach to deliver genes Pdx1, Ngn3 (Neurog3) and MafA singly and in combination to livers of normoglycaemic rats. |
| 4454 | 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. |
| 4455 | 22685335 | We used the hydrodynamic approach to deliver genes Pdx1, Ngn3 (Neurog3) and MafA singly and in combination to livers of normoglycaemic rats. |
| 4456 | 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. |
| 4457 | 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. |
| 4458 | 22761699 | Here, we demonstrate that CXCR4 and SDF-1α are expressed in the human fetal pancreas and that during early gestation, CXCR4 colocalizes with neurogenin 3 (ngn3), a key transcription factor for endocrine specification in the pancreas. |
| 4459 | 22761699 | Exposure of ICCs in vitro to AMD3100, a pharmacological inhibitor of CXCR4, did not alter expression of endocrine hormones insulin and glucagon, or the pancreatic endocrine transcription factors PDX1, Nkx6.1, Ngn3 and PAX4. |
| 4460 | 22790351 | Decreased expression of insulin and increased expression of pancreatic transcription factor PDX-1 in islets in patients with liver cirrhosis: a comparative investigation using human autopsy specimens. |
| 4461 | 22819546 | Small molecule kaempferol modulates PDX-1 protein expression and subsequently promotes pancreatic β-cell survival and function via CREB. |
| 4462 | 22819546 | In addition, kaempferol prevented the lipotoxicity-induced down-regulation of antiapoptotic proteins Akt and Bcl-2. |
| 4463 | 22819546 | The cytoprotective effects of kaempferol were associated with improved insulin secretion, synthesis, and pancreatic and duodenal homeobox-1 (PDX-1) expression. |
| 4464 | 22819546 | Chronic hyperlipidemia significantly diminished cyclic adenosine monophosphate (cAMP) production, protein kinase A (PKA) activation, cAMP-responsive element binding protein (CREB) phosphorylation and its regulated transcriptional activity in β-cells, all of which were restored by kaempferol treatment. |
| 4465 | 22819546 | PDX-1 gene knockdown reduced kaempferol-stimulated cAMP generation and CREB activation in INS-1E cells. |
| 4466 | 22819546 | These findings demonstrate that kaempferol is a novel survivor factor for pancreatic β-cells via up-regulating the PDX-1/cAMP/PKA/CREB signaling cascade. |
| 4467 | 22819546 | Small molecule kaempferol modulates PDX-1 protein expression and subsequently promotes pancreatic β-cell survival and function via CREB. |
| 4468 | 22819546 | In addition, kaempferol prevented the lipotoxicity-induced down-regulation of antiapoptotic proteins Akt and Bcl-2. |
| 4469 | 22819546 | The cytoprotective effects of kaempferol were associated with improved insulin secretion, synthesis, and pancreatic and duodenal homeobox-1 (PDX-1) expression. |
| 4470 | 22819546 | Chronic hyperlipidemia significantly diminished cyclic adenosine monophosphate (cAMP) production, protein kinase A (PKA) activation, cAMP-responsive element binding protein (CREB) phosphorylation and its regulated transcriptional activity in β-cells, all of which were restored by kaempferol treatment. |
| 4471 | 22819546 | PDX-1 gene knockdown reduced kaempferol-stimulated cAMP generation and CREB activation in INS-1E cells. |
| 4472 | 22819546 | These findings demonstrate that kaempferol is a novel survivor factor for pancreatic β-cells via up-regulating the PDX-1/cAMP/PKA/CREB signaling cascade. |
| 4473 | 22819546 | Small molecule kaempferol modulates PDX-1 protein expression and subsequently promotes pancreatic β-cell survival and function via CREB. |
| 4474 | 22819546 | In addition, kaempferol prevented the lipotoxicity-induced down-regulation of antiapoptotic proteins Akt and Bcl-2. |
| 4475 | 22819546 | The cytoprotective effects of kaempferol were associated with improved insulin secretion, synthesis, and pancreatic and duodenal homeobox-1 (PDX-1) expression. |
| 4476 | 22819546 | Chronic hyperlipidemia significantly diminished cyclic adenosine monophosphate (cAMP) production, protein kinase A (PKA) activation, cAMP-responsive element binding protein (CREB) phosphorylation and its regulated transcriptional activity in β-cells, all of which were restored by kaempferol treatment. |
| 4477 | 22819546 | PDX-1 gene knockdown reduced kaempferol-stimulated cAMP generation and CREB activation in INS-1E cells. |
| 4478 | 22819546 | These findings demonstrate that kaempferol is a novel survivor factor for pancreatic β-cells via up-regulating the PDX-1/cAMP/PKA/CREB signaling cascade. |
| 4479 | 22819546 | Small molecule kaempferol modulates PDX-1 protein expression and subsequently promotes pancreatic β-cell survival and function via CREB. |
| 4480 | 22819546 | In addition, kaempferol prevented the lipotoxicity-induced down-regulation of antiapoptotic proteins Akt and Bcl-2. |
| 4481 | 22819546 | The cytoprotective effects of kaempferol were associated with improved insulin secretion, synthesis, and pancreatic and duodenal homeobox-1 (PDX-1) expression. |
| 4482 | 22819546 | Chronic hyperlipidemia significantly diminished cyclic adenosine monophosphate (cAMP) production, protein kinase A (PKA) activation, cAMP-responsive element binding protein (CREB) phosphorylation and its regulated transcriptional activity in β-cells, all of which were restored by kaempferol treatment. |
| 4483 | 22819546 | PDX-1 gene knockdown reduced kaempferol-stimulated cAMP generation and CREB activation in INS-1E cells. |
| 4484 | 22819546 | These findings demonstrate that kaempferol is a novel survivor factor for pancreatic β-cells via up-regulating the PDX-1/cAMP/PKA/CREB signaling cascade. |
| 4485 | 22819839 | Geniposide could prevent oxidative stress-induced neuron apoptosis, and improved glucose stimulated insulin secretion by activating glucagon-like peptide 1 receptor (GLP-1R) in INS-1 cells. |
| 4486 | 22819839 | Moreover, geniposide also improved the impairment of GLP-1R signaling through enhancing the phosphorylation of Akt and Foxo1, and increased the expression of PDX-1 in palmitate-treated INS-1 cells. |
| 4487 | 22833839 | These islet-like cells expressed multiple genes related to islet development and beta cell function (e.g., Pdx-1, Ngn-3, Islet-1, Neuro-D, Pax4, IAPP, and insulin) and produced insulin and C-peptide within these cells. |
| 4488 | 22833839 | However, these transplanted differentiated cells became tumorigenic in diabetic immunocompromised mice and their spontaneous transformation was confirmed by a marked increase in growth rate and inactivation of tumor suppressor genes (P21 and P16) by promoter hypermethylation. |
| 4489 | 22841397 | Insulin secretion increased from the islets of biotin-supplemented mice, together with the messenger RNA (mRNA) expression of several transcription factors regulating insulin expression and secretion, including forkhead box A2, pancreatic and duodenal homeobox 1 and hepatocyte nuclear factor 4α. |
| 4490 | 22841397 | The mRNA abundance of glucokinase, Cacna1d, acetyl-CoA carboxylase, and insulin also increased. |
| 4491 | 22902430 | We tested the effects of two types of three-dimensional scaffolds, collagen matrix (CM) and fibroblast-populated collagen matrix (FPCM), on amyloid formation, viability, and function of isolated islets. |
| 4492 | 22902430 | IL-1β and Fas levels were also reduced in scaffold-embedded islets. |
| 4493 | 22902430 | Moreover, culture in CM and FPCM (but not 2D) preserved insulin, GLUT-2, and PDX-1 mRNA expression. |
| 4494 | 22902430 | FPCM-embedded islets had significantly higher insulin response and lower amyloid formation than CM-embedded islets. |
| 4495 | 22915381 | Moreover, reverse transcription-polymerase chain reaction (RT-PCR) data showed increased expression of pancreatic cell markers, including insulin, Pdx1, pan polypeptide and neurogenin-3, when these cells formed pancreatic clusters in the presence of activin A, exendin-4 and retinoic acid. |
| 4496 | 22946080 | Moreover, OP, NP, or BPA (25 μg/l) impaired mitochondrial function in β-cells and induced remarkable swelling of mitochondria with loss of distinct cristae structure within the membrane, which was accompanied by disruption of mRNA expression of genes playing a key role in β-cell function (Glut2 (Slc2a2), Gck, Pdx1, Hnf1α, Rab27a, and Snap25), and mitochondrial function (Ucp2 and Ogdh). |
| 4497 | 22960178 | These DE cells could further differentiate into PDX1 and NKX6.1 positive pancreatic progenitors in vitro. |
| 4498 | 23008108 | Characterization of insulin-producing cells derived from PDX-1-transfected neural stem cells. |
| 4499 | 23008108 | In vitro transfection of the pancreatic duodenal homeobox-1 (PDX-1) gene into NSCs generated insulin‑producing cells. |
| 4500 | 23008108 | Reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) analysis confirmed that PDX-1-transfected NSCs expressed insulin mRNA and released insulin protein. |
| 4501 | 23008108 | However, insulin release from PDX-1-transfected NSCs did not respond to the challenge of glucose and glucagon-like peptide-1. |
| 4502 | 23008108 | Characterization of insulin-producing cells derived from PDX-1-transfected neural stem cells. |
| 4503 | 23008108 | In vitro transfection of the pancreatic duodenal homeobox-1 (PDX-1) gene into NSCs generated insulin‑producing cells. |
| 4504 | 23008108 | Reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) analysis confirmed that PDX-1-transfected NSCs expressed insulin mRNA and released insulin protein. |
| 4505 | 23008108 | However, insulin release from PDX-1-transfected NSCs did not respond to the challenge of glucose and glucagon-like peptide-1. |
| 4506 | 23008108 | Characterization of insulin-producing cells derived from PDX-1-transfected neural stem cells. |
| 4507 | 23008108 | In vitro transfection of the pancreatic duodenal homeobox-1 (PDX-1) gene into NSCs generated insulin‑producing cells. |
| 4508 | 23008108 | Reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) analysis confirmed that PDX-1-transfected NSCs expressed insulin mRNA and released insulin protein. |
| 4509 | 23008108 | However, insulin release from PDX-1-transfected NSCs did not respond to the challenge of glucose and glucagon-like peptide-1. |
| 4510 | 23008108 | Characterization of insulin-producing cells derived from PDX-1-transfected neural stem cells. |
| 4511 | 23008108 | In vitro transfection of the pancreatic duodenal homeobox-1 (PDX-1) gene into NSCs generated insulin‑producing cells. |
| 4512 | 23008108 | Reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) analysis confirmed that PDX-1-transfected NSCs expressed insulin mRNA and released insulin protein. |
| 4513 | 23008108 | However, insulin release from PDX-1-transfected NSCs did not respond to the challenge of glucose and glucagon-like peptide-1. |
| 4514 | 23012647 | Deletion of β-Catenin in Pdx1 pancreatic progenitors leads to a decreased β-cell mass and impaired glucose tolerance. |
| 4515 | 23012647 | Surprisingly, loss of β-catenin made these mice resistant to high fat diet because of their increased energy expenditure and insulin sensitivity due to hyperactivity. |
| 4516 | 23022408 | We observed that AK (10mg/kg bw) exerted peroxisome proliferator-activated receptor-γ (PPARγ) agonist activity, thereby enhancing insulin sensitivity (as indicated by hepatic GLUT2 translocation, PTP1B suppression, and glucose uptake) by downregulating blood glucose and upregulating pancreatic and duodenal homeobox-1 and Maf-A expression and increasing insulin production in MG-induced rats. |
| 4517 | 23022408 | However, these effects were abolished by the administration of GW9662 (PPARγ antagonist), but the expression of hepatic heme oxygenase-1 (HO-1) and glutamate-cysteine ligase (GCL) was not suppressed in MG-induced rats. |
| 4518 | 23022408 | AK did not affect hepatic Nrf2 mRNA or protein expression but significantly increased Nrf2 phosphorylation (serine 40), which was accompanied by increased transcriptional activation of hepatic HO-1 and GCL. |
| 4519 | 23022408 | We also found that AK treatment reduced the production of inflammatory factors, such as tumor necrosis factor-α and interleukin-1β. |
| 4520 | 23022408 | Taken together, the results of our mechanistic study of MG-induced rats suggest that the protective effects of AK against diabetes are mediated by the upregulation of the signaling pathway of Nrf2, which enhances antioxidant activity and serves as a PPARγ agonist to enhance insulin sensitivity. |
| 4521 | 23077629 | We previously delivered adenovirus vector (AdV) into exocrine cells of the pancreas by intra-common bile ductal (ICBD) injection, and found that AdV expressing Pdx1, a pancreas-specific transcription factor, causes TC formation and islet neogenesis. |
| 4522 | 23077629 | AdV expressing Isl1, a proendocrine transcription factor, effectively induced TC formation through acinar-to-ductal metaplasia, and exogenous Pdx1 expression facilitated this process. |
| 4523 | 23077629 | We previously delivered adenovirus vector (AdV) into exocrine cells of the pancreas by intra-common bile ductal (ICBD) injection, and found that AdV expressing Pdx1, a pancreas-specific transcription factor, causes TC formation and islet neogenesis. |
| 4524 | 23077629 | AdV expressing Isl1, a proendocrine transcription factor, effectively induced TC formation through acinar-to-ductal metaplasia, and exogenous Pdx1 expression facilitated this process. |
| 4525 | 23147208 | Triiodothyronine (T3) induces proinsulin gene expression by activating PI3K: possible roles for GSK-3β and the transcriptional factor PDX-1. |
| 4526 | 23147208 | Thyroid hormone (TH) activates PI3K and Akt, leading to glucose uptake in rat skeletal muscle cells and proliferation of insulinoma cells, respectively. |
| 4527 | 23147208 | However, TH actions on pancreatic beta cells have been little explored, which lead us to evaluate the TH eff ects on proinsulin gene expression, and the involvement of PI3K/Akt/GSK-3β signaling pathway, and a transcriptional factor for insulin (PDX-1). |
| 4528 | 23147208 | Proinsulin mRNA expression was evaluated by real time PCR, and pGSK-3β and PDX-1 protein content was analyzed by Western blotting. |
| 4529 | 23147208 | ActD, CHX and wortmannin, but not Akt inhibitor, prevented the rapid stimulatory eff ect of T3 on proinsulin mRNA expression. |
| 4530 | 23147208 | These data indicate that T3 acutely increases proinsulin mRNA expression, by mechanisms which depends on the activation of PI3K, but not of Akt, and may involve the inactivation of GSK-3β by phosphorylation. |
| 4531 | 23147208 | Considering that PDX-1 is one of the most important transcriptional factors for proinsulin gene expression, its enhancement may underlie the increased proinsulin mRNA content acutely induced by T3. |
| 4532 | 23147208 | Triiodothyronine (T3) induces proinsulin gene expression by activating PI3K: possible roles for GSK-3β and the transcriptional factor PDX-1. |
| 4533 | 23147208 | Thyroid hormone (TH) activates PI3K and Akt, leading to glucose uptake in rat skeletal muscle cells and proliferation of insulinoma cells, respectively. |
| 4534 | 23147208 | However, TH actions on pancreatic beta cells have been little explored, which lead us to evaluate the TH eff ects on proinsulin gene expression, and the involvement of PI3K/Akt/GSK-3β signaling pathway, and a transcriptional factor for insulin (PDX-1). |
| 4535 | 23147208 | Proinsulin mRNA expression was evaluated by real time PCR, and pGSK-3β and PDX-1 protein content was analyzed by Western blotting. |
| 4536 | 23147208 | ActD, CHX and wortmannin, but not Akt inhibitor, prevented the rapid stimulatory eff ect of T3 on proinsulin mRNA expression. |
| 4537 | 23147208 | These data indicate that T3 acutely increases proinsulin mRNA expression, by mechanisms which depends on the activation of PI3K, but not of Akt, and may involve the inactivation of GSK-3β by phosphorylation. |
| 4538 | 23147208 | Considering that PDX-1 is one of the most important transcriptional factors for proinsulin gene expression, its enhancement may underlie the increased proinsulin mRNA content acutely induced by T3. |
| 4539 | 23147208 | Triiodothyronine (T3) induces proinsulin gene expression by activating PI3K: possible roles for GSK-3β and the transcriptional factor PDX-1. |
| 4540 | 23147208 | Thyroid hormone (TH) activates PI3K and Akt, leading to glucose uptake in rat skeletal muscle cells and proliferation of insulinoma cells, respectively. |
| 4541 | 23147208 | However, TH actions on pancreatic beta cells have been little explored, which lead us to evaluate the TH eff ects on proinsulin gene expression, and the involvement of PI3K/Akt/GSK-3β signaling pathway, and a transcriptional factor for insulin (PDX-1). |
| 4542 | 23147208 | Proinsulin mRNA expression was evaluated by real time PCR, and pGSK-3β and PDX-1 protein content was analyzed by Western blotting. |
| 4543 | 23147208 | ActD, CHX and wortmannin, but not Akt inhibitor, prevented the rapid stimulatory eff ect of T3 on proinsulin mRNA expression. |
| 4544 | 23147208 | These data indicate that T3 acutely increases proinsulin mRNA expression, by mechanisms which depends on the activation of PI3K, but not of Akt, and may involve the inactivation of GSK-3β by phosphorylation. |
| 4545 | 23147208 | Considering that PDX-1 is one of the most important transcriptional factors for proinsulin gene expression, its enhancement may underlie the increased proinsulin mRNA content acutely induced by T3. |
| 4546 | 23147208 | Triiodothyronine (T3) induces proinsulin gene expression by activating PI3K: possible roles for GSK-3β and the transcriptional factor PDX-1. |
| 4547 | 23147208 | Thyroid hormone (TH) activates PI3K and Akt, leading to glucose uptake in rat skeletal muscle cells and proliferation of insulinoma cells, respectively. |
| 4548 | 23147208 | However, TH actions on pancreatic beta cells have been little explored, which lead us to evaluate the TH eff ects on proinsulin gene expression, and the involvement of PI3K/Akt/GSK-3β signaling pathway, and a transcriptional factor for insulin (PDX-1). |
| 4549 | 23147208 | Proinsulin mRNA expression was evaluated by real time PCR, and pGSK-3β and PDX-1 protein content was analyzed by Western blotting. |
| 4550 | 23147208 | ActD, CHX and wortmannin, but not Akt inhibitor, prevented the rapid stimulatory eff ect of T3 on proinsulin mRNA expression. |
| 4551 | 23147208 | These data indicate that T3 acutely increases proinsulin mRNA expression, by mechanisms which depends on the activation of PI3K, but not of Akt, and may involve the inactivation of GSK-3β by phosphorylation. |
| 4552 | 23147208 | Considering that PDX-1 is one of the most important transcriptional factors for proinsulin gene expression, its enhancement may underlie the increased proinsulin mRNA content acutely induced by T3. |
| 4553 | 23153982 | Mechanisms and techniques of reprogramming: using PDX-1 homeobox protein as a novel treatment of insulin dependent diabetes mellitus. |
| 4554 | 23153982 | Pancreatic Duodenal Homeobox-1 (PDX-1) is a homeobox protein which acts as a key regulator in the development of b cells in the Islets of Langerhans. |
| 4555 | 23153982 | There is strong evidence that PDX-1 plays a role in activating the insulin promoter and increasing insulin levels in response to glucose. |
| 4556 | 23153982 | PDX-1 also binds to sequences within β cells and regulates the promoter activity of a number of islet genes including insulin, glut-2 and neurogenin 3. |
| 4557 | 23153982 | When fused with the VP16 activation sequence, transfection of the PDX-1 gene has been shown to transform liver cells into insulin producing cells. |
| 4558 | 23153982 | Mechanisms and techniques of reprogramming: using PDX-1 homeobox protein as a novel treatment of insulin dependent diabetes mellitus. |
| 4559 | 23153982 | Pancreatic Duodenal Homeobox-1 (PDX-1) is a homeobox protein which acts as a key regulator in the development of b cells in the Islets of Langerhans. |
| 4560 | 23153982 | There is strong evidence that PDX-1 plays a role in activating the insulin promoter and increasing insulin levels in response to glucose. |
| 4561 | 23153982 | PDX-1 also binds to sequences within β cells and regulates the promoter activity of a number of islet genes including insulin, glut-2 and neurogenin 3. |
| 4562 | 23153982 | When fused with the VP16 activation sequence, transfection of the PDX-1 gene has been shown to transform liver cells into insulin producing cells. |
| 4563 | 23153982 | Mechanisms and techniques of reprogramming: using PDX-1 homeobox protein as a novel treatment of insulin dependent diabetes mellitus. |
| 4564 | 23153982 | Pancreatic Duodenal Homeobox-1 (PDX-1) is a homeobox protein which acts as a key regulator in the development of b cells in the Islets of Langerhans. |
| 4565 | 23153982 | There is strong evidence that PDX-1 plays a role in activating the insulin promoter and increasing insulin levels in response to glucose. |
| 4566 | 23153982 | PDX-1 also binds to sequences within β cells and regulates the promoter activity of a number of islet genes including insulin, glut-2 and neurogenin 3. |
| 4567 | 23153982 | When fused with the VP16 activation sequence, transfection of the PDX-1 gene has been shown to transform liver cells into insulin producing cells. |
| 4568 | 23153982 | Mechanisms and techniques of reprogramming: using PDX-1 homeobox protein as a novel treatment of insulin dependent diabetes mellitus. |
| 4569 | 23153982 | Pancreatic Duodenal Homeobox-1 (PDX-1) is a homeobox protein which acts as a key regulator in the development of b cells in the Islets of Langerhans. |
| 4570 | 23153982 | There is strong evidence that PDX-1 plays a role in activating the insulin promoter and increasing insulin levels in response to glucose. |
| 4571 | 23153982 | PDX-1 also binds to sequences within β cells and regulates the promoter activity of a number of islet genes including insulin, glut-2 and neurogenin 3. |
| 4572 | 23153982 | When fused with the VP16 activation sequence, transfection of the PDX-1 gene has been shown to transform liver cells into insulin producing cells. |
| 4573 | 23153982 | Mechanisms and techniques of reprogramming: using PDX-1 homeobox protein as a novel treatment of insulin dependent diabetes mellitus. |
| 4574 | 23153982 | Pancreatic Duodenal Homeobox-1 (PDX-1) is a homeobox protein which acts as a key regulator in the development of b cells in the Islets of Langerhans. |
| 4575 | 23153982 | There is strong evidence that PDX-1 plays a role in activating the insulin promoter and increasing insulin levels in response to glucose. |
| 4576 | 23153982 | PDX-1 also binds to sequences within β cells and regulates the promoter activity of a number of islet genes including insulin, glut-2 and neurogenin 3. |
| 4577 | 23153982 | When fused with the VP16 activation sequence, transfection of the PDX-1 gene has been shown to transform liver cells into insulin producing cells. |
| 4578 | 23247113 | Previously, it was found that during pregnancy, heterozygous prolactin receptor-null (Prlr(+/-)) mice had lower number of β-cells, lower serum insulin and higher blood glucose levels than wild-type (Prlr(+/+)) mice. |
| 4579 | 23247113 | Pathways that are known to regulate β-cell proliferation during pregnancy include insulin receptor substrate-2, Akt, menin, the serotonin synthetic enzyme tryptophan hydroxylase-1, Forkhead box M1 and Forkhead box D3. |
| 4580 | 23247113 | It was found that the pregnancy-induced increases in insulin receptor substrate-2 and Akt expression in the islets were attenuated in the Prlr(+/+(+/-)) mice in comparison to the Prlr(+/+(+/+)) mice. |
| 4581 | 23247113 | The expression of Forkhead box D3, which plays a permissive role for β-cell proliferation during pregnancy, was also lower in the Prlr(+/+(+/-)) mice. |
| 4582 | 23247113 | In contrast, the pregnancy-induced increases in phospho-Jak2, tryptophan hydroxylase-1 and FoxM1, as well as the pregnancy-associated reduction in menin expression, were comparable between the two groups. |
| 4583 | 23247113 | There was also no difference in expression levels of genes that regulate insulin synthesis and secretion (i.e. glucose transporter 2, glucokinase and pancreatic and duodenal homeobox-1) between these two groups. |
| 4584 | 23247113 | Taken together, these results suggest that the in utero environment of the Prlr(+/-) mother confers long-term changes in the pancreatic islets of her offspring such that when the offspring themselves became pregnant, they cannot adapt to the increased insulin demands of their own pregnancy. |
| 4585 | 23271274 | Furthermore, RT-PCR results confirmed the expression of insulin, PDX1, Ngn3, PAX4, and GLUT2 in differentiated cells. |
| 4586 | 23271432 | The results reveal that mesenchymal stem cells (MSC) derived from bone marrow and subcutaneous adipose tissue can differentiate into pancreatic islet-like clusters, as evidenced by their islet-like morphology, positive dithizone staining and expression of genes such as Nestin, PDX1, Isl 1, Ngn 3, Pax 4 and Insulin. |
| 4587 | 23306211 | RT-PCR for endodermal and pancreatic lineage-specific markers was performed on AFS cells after adenovirally transduced expression of PDX1, NGN3 and MAFA. |
| 4588 | 23306211 | Expression of MAFA was sufficient to induce insulin mRNA expression in nhpAFS cell lines, whereas a combination of MAFA, PDX1 and NGN3 further induced insulin expression, and also induced the expression of other important endocrine cell genes such as glucagon, NEUROD1, NKX2.2, ISL1 and PCSK2. |
| 4589 | 23306211 | The expression of pancreatic genes such as NEUROD1, glucagon and insulin progressively decreased with the decline of adenovirally expressed PDX1, NGN3 and MAFA. |
| 4590 | 23306211 | RT-PCR for endodermal and pancreatic lineage-specific markers was performed on AFS cells after adenovirally transduced expression of PDX1, NGN3 and MAFA. |
| 4591 | 23306211 | Expression of MAFA was sufficient to induce insulin mRNA expression in nhpAFS cell lines, whereas a combination of MAFA, PDX1 and NGN3 further induced insulin expression, and also induced the expression of other important endocrine cell genes such as glucagon, NEUROD1, NKX2.2, ISL1 and PCSK2. |
| 4592 | 23306211 | The expression of pancreatic genes such as NEUROD1, glucagon and insulin progressively decreased with the decline of adenovirally expressed PDX1, NGN3 and MAFA. |
| 4593 | 23306211 | RT-PCR for endodermal and pancreatic lineage-specific markers was performed on AFS cells after adenovirally transduced expression of PDX1, NGN3 and MAFA. |
| 4594 | 23306211 | Expression of MAFA was sufficient to induce insulin mRNA expression in nhpAFS cell lines, whereas a combination of MAFA, PDX1 and NGN3 further induced insulin expression, and also induced the expression of other important endocrine cell genes such as glucagon, NEUROD1, NKX2.2, ISL1 and PCSK2. |
| 4595 | 23306211 | The expression of pancreatic genes such as NEUROD1, glucagon and insulin progressively decreased with the decline of adenovirally expressed PDX1, NGN3 and MAFA. |
| 4596 | 23313787 | Expression profiles of genes involved in metabolic and signaling functions of pancreatic cells (Ins, Glut1/2/3, Pdx1, Reg1α) were similar between fresh cells and those cryopreserved with the plant protein formulation. |
| 4597 | 23339089 | Recombinant human Pdx1 proteins (hPdx1), which have an Antennapedia-like protein transduction domain sequence in their structure, can be efficiently translocated into hES cells and function as pancreatic transcription factor. hPdx1 protein activates a group of genes related to pancreatic beta-cell lineage development in hES cells, including NeuroD1, Nkx2.2, Pax4, Pax6, Nkx6.1 and Isl-1. hPdx1-treated hES cells synthesise and release insulin in response to glucose challenge. |
| 4598 | 23349497 | In vivo JNK activation in pancreatic β-cells leads to glucose intolerance caused by insulin resistance in pancreas. |
| 4599 | 23349497 | It is well established that exacerbated Jun NH2-terminal kinase (JNK) activity is involved in promoting insulin resistance in peripheral insulin-target tissues; however, this involvement is less documented in pancreatic β-cells. |
| 4600 | 23349497 | At the molecular level, JNK activation in β-cells inhibited insulin-induced Akt phosphorylation, pancreatic and duodenal homeobox 1 nucleocytoplasmic shuttling, and transcription of insulin-target genes. |
| 4601 | 23349497 | In conclusion, the mere activation of JNK suffices to induce insulin resistance in pancreatic β-cells by inhibition of insulin signaling in these cells, but it is not sufficient to elicit β-cell death. |
| 4602 | 23378917 | An essential step in this protocol was the generation of pancreatic precursor cell that express Pdx1 based on induction by a combination of 5-aza-2'-deoxycytidine, trichostatin A, retinoic acid, and a mix of insulin, transferrin and selenite. |
| 4603 | 23382448 | Dicer1-deficient β-cells lost insulin expression while maintaining the expression of β-cell transcription factors such as Pdx1 and Nkx6.1 early in the postnatal period. |
| 4604 | 23434589 | Indeed, we show that treatment of cultured pancreatic islets with a histone methyltransferase inhibitor leads to colocalization of both glucagon and insulin and glucagon and insulin promoter factor 1 (PDX1) in human islets and colocalization of both glucagon and insulin in mouse islets. |
| 4605 | 23449893 | The cultured infant islets expressed pancreatic and duodenal homeobox 1 and several (Glut1, Cav1.3, Kir6.2) but not all (syntaxin 1A and synaptosomal-associated protein 25) markers of functional islets, suggesting a loss of secretory phenotype in culture. |
| 4606 | 23449893 | After a 24- to 28-day expansion and maturation protocol, we found preservation of endocrine markers and hormone expression, an increased proportion of insulin-positive cells, elevated expression of syntaxin 1A and synaptosomal-associated protein 25, and restoration of exocytosis to levels comparable with that in adult β-cells. |
| 4607 | 23463236 | Persistent effects of an early suboptimal environment, known to increase risk of type 2 diabetes in later life, can alter the epigenetic control of transcriptional master regulators, such as Hnf4a and Pdx1. |
| 4608 | 23468018 | We found that PDX1 positive pancreatic progenitors proliferated and gained NKX6.1 expression in the PM, whereas they failed to express NKX6.1 if BMP signaling was inhibited with Noggin. |
| 4609 | 23468018 | On the contrary, addition of BMP4 to the PM promoted the early derivation of PDX1 and NKX6.1 coexpressing pancreatic progenitors. |
| 4610 | 23468018 | Our findings are in line with mouse pancreas development, and indicate that BMP4 signaling is required for the derivation and maintenance of hESC-derived PDX1+NKX6.1+ pancreatic progenitors. |
| 4611 | 23468018 | We found that PDX1 positive pancreatic progenitors proliferated and gained NKX6.1 expression in the PM, whereas they failed to express NKX6.1 if BMP signaling was inhibited with Noggin. |
| 4612 | 23468018 | On the contrary, addition of BMP4 to the PM promoted the early derivation of PDX1 and NKX6.1 coexpressing pancreatic progenitors. |
| 4613 | 23468018 | Our findings are in line with mouse pancreas development, and indicate that BMP4 signaling is required for the derivation and maintenance of hESC-derived PDX1+NKX6.1+ pancreatic progenitors. |
| 4614 | 23468018 | We found that PDX1 positive pancreatic progenitors proliferated and gained NKX6.1 expression in the PM, whereas they failed to express NKX6.1 if BMP signaling was inhibited with Noggin. |
| 4615 | 23468018 | On the contrary, addition of BMP4 to the PM promoted the early derivation of PDX1 and NKX6.1 coexpressing pancreatic progenitors. |
| 4616 | 23468018 | Our findings are in line with mouse pancreas development, and indicate that BMP4 signaling is required for the derivation and maintenance of hESC-derived PDX1+NKX6.1+ pancreatic progenitors. |
| 4617 | 23486591 | Tetrapeptide pancragen stimulates the expression of differentiation factors of acinar (Pdx1, Ptfla) and islet of Langerhans (Pdx1, Pax6, Pax4, Foxa2, NKx2.2) cells in "young" and " aged" cultures. |
| 4618 | 23533474 | Quercetin Preserves β -Cell Mass and Function in Fructose-Induced Hyperinsulinemia through Modulating Pancreatic Akt/FoxO1 Activation. |
| 4619 | 23533474 | Quercetin was confirmed to reduce serum insulin and leptin levels and blockade islet hyperplasia in fructose-fed rats. |
| 4620 | 23533474 | It also prevented fructose-induced β -cell proliferation and insulin hypersecretion in INS-1 β -cells. |
| 4621 | 23533474 | Quercetin downregulated Akt and FoxO1 phosphorylation in fructose-fed rat islets and increased the nuclear FoxO1 levels in fructose-treated INS-1 β -cells. |
| 4622 | 23533474 | The elevated Akt phosphorylation in fructose-treated INS-1 β -cells was also restored by quercetin. |
| 4623 | 23533474 | Additionally, quercetin suppressed the expression of pancreatic and duodenal homeobox 1 (Pdx1) and insulin gene (Ins1 and Ins2) in vivo and in vitro. |
| 4624 | 23533474 | In fructose-treated INS-1 β -cells, quercetin elevated the reduced janus kinase 2/signal transducers and activators of transcription 3 (Jak2/Stat3) phosphorylation and suppressed the increased suppressor of cytokine signaling 3 (Socs3) expression. |
| 4625 | 23533474 | These results demonstrate that quercetin protects β -cell mass and function under high-fructose induction through improving leptin signaling and preserving pancreatic Akt/FoxO1 activation. |
| 4626 | 23562832 | Adenoviral-mediated expression of NEUROG3, Pdx1, and MafA in GBCs resulted in robust induction of pancreatic endocrine genes, including Ins1, Ins2, Neurod1, Nkx2-2 and Isl1. |
| 4627 | 23562832 | Furthermore, expression of GBC-specific genes was repressed, including Sox17 and Hes1. |
| 4628 | 23569174 | Transition of β-cells into α-cells occurs after β-cell degranulation and is characterized by the presence of β-cell-specific transcription factors Pdx1 and Nkx6.1 in glucagon(+) cells. |
| 4629 | 23586830 | The objective of this study was to evaluate the potential of lentivirus to introduce the PDX1 gene into MSCs to produce insulin-secreting cells and apply it for treatment of hyperglycemia in diabetic rats. |
| 4630 | 23586830 | Significant expressions of PDX1, neurogenin3, glucagon, glucose transporter2 (Glut2), and insulin were detected by quantitative reverse transcription-polymerase chain reaction (P < 0.05). |
| 4631 | 23586830 | PDX1 and insulin were detected at the protein level by immunofluorescence analysis. |
| 4632 | 23586830 | PDX1 could trigger a gene expression cascade that involved pancreatic endocrine differentiation and also revealed the glucose sensing ability by expressing Glut2 in high-glucose medium. |
| 4633 | 23586830 | The insulin secretion of MSCs(PDX1+) in the high-glucose medium was 1.75-fold higher than that secreted in the low-glucose medium (P < 0.05). |
| 4634 | 23586830 | The objective of this study was to evaluate the potential of lentivirus to introduce the PDX1 gene into MSCs to produce insulin-secreting cells and apply it for treatment of hyperglycemia in diabetic rats. |
| 4635 | 23586830 | Significant expressions of PDX1, neurogenin3, glucagon, glucose transporter2 (Glut2), and insulin were detected by quantitative reverse transcription-polymerase chain reaction (P < 0.05). |
| 4636 | 23586830 | PDX1 and insulin were detected at the protein level by immunofluorescence analysis. |
| 4637 | 23586830 | PDX1 could trigger a gene expression cascade that involved pancreatic endocrine differentiation and also revealed the glucose sensing ability by expressing Glut2 in high-glucose medium. |
| 4638 | 23586830 | The insulin secretion of MSCs(PDX1+) in the high-glucose medium was 1.75-fold higher than that secreted in the low-glucose medium (P < 0.05). |
| 4639 | 23586830 | The objective of this study was to evaluate the potential of lentivirus to introduce the PDX1 gene into MSCs to produce insulin-secreting cells and apply it for treatment of hyperglycemia in diabetic rats. |
| 4640 | 23586830 | Significant expressions of PDX1, neurogenin3, glucagon, glucose transporter2 (Glut2), and insulin were detected by quantitative reverse transcription-polymerase chain reaction (P < 0.05). |
| 4641 | 23586830 | PDX1 and insulin were detected at the protein level by immunofluorescence analysis. |
| 4642 | 23586830 | PDX1 could trigger a gene expression cascade that involved pancreatic endocrine differentiation and also revealed the glucose sensing ability by expressing Glut2 in high-glucose medium. |
| 4643 | 23586830 | The insulin secretion of MSCs(PDX1+) in the high-glucose medium was 1.75-fold higher than that secreted in the low-glucose medium (P < 0.05). |
| 4644 | 23586830 | The objective of this study was to evaluate the potential of lentivirus to introduce the PDX1 gene into MSCs to produce insulin-secreting cells and apply it for treatment of hyperglycemia in diabetic rats. |
| 4645 | 23586830 | Significant expressions of PDX1, neurogenin3, glucagon, glucose transporter2 (Glut2), and insulin were detected by quantitative reverse transcription-polymerase chain reaction (P < 0.05). |
| 4646 | 23586830 | PDX1 and insulin were detected at the protein level by immunofluorescence analysis. |
| 4647 | 23586830 | PDX1 could trigger a gene expression cascade that involved pancreatic endocrine differentiation and also revealed the glucose sensing ability by expressing Glut2 in high-glucose medium. |
| 4648 | 23586830 | The insulin secretion of MSCs(PDX1+) in the high-glucose medium was 1.75-fold higher than that secreted in the low-glucose medium (P < 0.05). |
| 4649 | 23586830 | The objective of this study was to evaluate the potential of lentivirus to introduce the PDX1 gene into MSCs to produce insulin-secreting cells and apply it for treatment of hyperglycemia in diabetic rats. |
| 4650 | 23586830 | Significant expressions of PDX1, neurogenin3, glucagon, glucose transporter2 (Glut2), and insulin were detected by quantitative reverse transcription-polymerase chain reaction (P < 0.05). |
| 4651 | 23586830 | PDX1 and insulin were detected at the protein level by immunofluorescence analysis. |
| 4652 | 23586830 | PDX1 could trigger a gene expression cascade that involved pancreatic endocrine differentiation and also revealed the glucose sensing ability by expressing Glut2 in high-glucose medium. |
| 4653 | 23586830 | The insulin secretion of MSCs(PDX1+) in the high-glucose medium was 1.75-fold higher than that secreted in the low-glucose medium (P < 0.05). |
| 4654 | 23595988 | Treatment with l-3,5,3-triiodothyronine increases the association of TRα with the p85α subunit of phosphatidylinositol 3-kinase (PI3K), leading to the phosphorylation and activation of Akt and the expression of Pdx1, Ngn3, and MafA in purified acinar cells. |
| 4655 | 23595988 | The inhibition of p85α expression by siRNA or the inhibition of PI3K by LY294002 prevents the expression of Pdx1, Ngn3, and MafA and the reprogramming to insulin-producing cells. |
| 4656 | 23595988 | Treatment with l-3,5,3-triiodothyronine increases the association of TRα with the p85α subunit of phosphatidylinositol 3-kinase (PI3K), leading to the phosphorylation and activation of Akt and the expression of Pdx1, Ngn3, and MafA in purified acinar cells. |
| 4657 | 23595988 | The inhibition of p85α expression by siRNA or the inhibition of PI3K by LY294002 prevents the expression of Pdx1, Ngn3, and MafA and the reprogramming to insulin-producing cells. |
| 4658 | 23606308 | These cells not only expressed MSC-specific markers like Sca-1, CD90.2, CD73, and CD44 but also generated osteocytes, adipocytes, and neurons when induced with specific growth media. |
| 4659 | 23606308 | Upon exposure to islet differentiation serum-free cocktail a significant upregulation of pancreatic markers like Nkx2.2, Nkx6.1, Pdx1, insulin, and somatostatin was seen. |
| 4660 | 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. |
| 4661 | 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. |
| 4662 | 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. |
| 4663 | 23624121 | These results suggest that co-transfection of Pdx1, Beta2 and Mafa induce insulin production in canine BMSCs. |
| 4664 | 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. |
| 4665 | 23624121 | These results suggest that co-transfection of Pdx1, Beta2 and Mafa induce insulin production in canine BMSCs. |
| 4666 | 23633267 | We present our experience of glucose-sensitive insulin-secreting mesenchymal stem cells (IS-MSC) generated and differentiated from human adipose tissue (h-AD) with application of specific differentiation media, sans xenogenic material. h-AD from donor abdominal wall was collected in proliferation medium composed of α-Minimum Essential Media, albumin, fibroblast-growth factor and antibiotics, minced, incubated in collagenase I at 37 °C with shaker and centrifuged. |
| 4667 | 23633267 | They were studied for transcriptional factors paired box genes-6(Pax-6), islet 1 transcriptional factor (Isl-1), pancreatic and duodenal homobox-1(Pdx-1). |
| 4668 | 23639568 | Permanent neonatal diabetes mellitus is a rare condition mostly due to heterozygous mutations in the KCNJ11, ABCC8 and INS genes. |
| 4669 | 23639568 | Mutations in PDX1, PTF1A, HNF1B, EIF2AK3, RFX6 and GATA6 genes have been shown to result in pancreatic agenesis or hypoplasia. |
| 4670 | 23650507 | However, isolated human islets displayed insulin signaling pathway resistance, due in part to chronic activation of mTOR/S6K1 signaling that results in negative feedback of the insulin signaling pathway and a loss of Akt phosphorylation and insulin content. |
| 4671 | 23650507 | This was associated with the restoration of IGF-1-induced phosphorylation of Akt, GSK-3, and increased protein expression of Pdx1. |
| 4672 | 23650507 | Furthermore, MSDC-0160 in combination with IGF-1 and 8 mM glucose increased β-cell specific gene expression of insulin, pdx1, nkx6.1, and nkx2.2, and maintained insulin content without altering glucose-stimulated insulin secretion. |
| 4673 | 23650507 | However, isolated human islets displayed insulin signaling pathway resistance, due in part to chronic activation of mTOR/S6K1 signaling that results in negative feedback of the insulin signaling pathway and a loss of Akt phosphorylation and insulin content. |
| 4674 | 23650507 | This was associated with the restoration of IGF-1-induced phosphorylation of Akt, GSK-3, and increased protein expression of Pdx1. |
| 4675 | 23650507 | Furthermore, MSDC-0160 in combination with IGF-1 and 8 mM glucose increased β-cell specific gene expression of insulin, pdx1, nkx6.1, and nkx2.2, and maintained insulin content without altering glucose-stimulated insulin secretion. |
| 4676 | 23671804 | The induced cells expressed multiple genes related to pancreatic beta-cell development and function, such as insulin1, glucagon, Pdx1, Pax6, and Glut-2. |
| 4677 | 23703573 | B-cell translocation gene 2 positively regulates GLP-1-stimulated insulin secretion via induction of PDX-1 in pancreatic β-cells. |
| 4678 | 23703573 | Here we demonstrate that B-cell translocation gene 2 (BTG2) is a crucial regulator in GLP-1-induced insulin gene expression and insulin secretion via upregulation of pancreatic duodenal homeobox-1 (PDX-1) in pancreatic β-cells. |
| 4679 | 23703573 | GLP-1 treatment significantly increased BTG2, PDX-1 and insulin gene expression in pancreatic β-cells. |
| 4680 | 23703573 | Notably, adenovirus-mediated overexpression of BTG2 significantly elevated insulin secretion, as well as insulin and PDX-1 gene expression. |
| 4681 | 23703573 | Physical interaction studies showed that BTG2 is associated with increased PDX-1 occupancy on the insulin gene promoter via a direct interaction with PDX-1. |
| 4682 | 23703573 | Exendin-4 (Ex-4), a GLP-1 agonist, and GLP-1 in pancreatic β-cells increased insulin secretion through the BTG2-PDX-1-insulin pathway, which was blocked by endogenous BTG2 knockdown using a BTG2 small interfering RNA knockdown system. |
| 4683 | 23703573 | Finally, we revealed that Ex-4 and GLP-1 significantly elevated insulin secretion via upregulation of the BTG2-PDX-1 axis in pancreatic islets, and this phenomenon was abolished by endogenous BTG2 knockdown. |
| 4684 | 23703573 | Collectively, our current study provides a novel molecular mechanism by which GLP-1 positively regulates insulin gene expression via BTG2, suggesting that BTG2 has a key function in insulin secretion in pancreatic β-cells. |
| 4685 | 23703573 | B-cell translocation gene 2 positively regulates GLP-1-stimulated insulin secretion via induction of PDX-1 in pancreatic β-cells. |
| 4686 | 23703573 | Here we demonstrate that B-cell translocation gene 2 (BTG2) is a crucial regulator in GLP-1-induced insulin gene expression and insulin secretion via upregulation of pancreatic duodenal homeobox-1 (PDX-1) in pancreatic β-cells. |
| 4687 | 23703573 | GLP-1 treatment significantly increased BTG2, PDX-1 and insulin gene expression in pancreatic β-cells. |
| 4688 | 23703573 | Notably, adenovirus-mediated overexpression of BTG2 significantly elevated insulin secretion, as well as insulin and PDX-1 gene expression. |
| 4689 | 23703573 | Physical interaction studies showed that BTG2 is associated with increased PDX-1 occupancy on the insulin gene promoter via a direct interaction with PDX-1. |
| 4690 | 23703573 | Exendin-4 (Ex-4), a GLP-1 agonist, and GLP-1 in pancreatic β-cells increased insulin secretion through the BTG2-PDX-1-insulin pathway, which was blocked by endogenous BTG2 knockdown using a BTG2 small interfering RNA knockdown system. |
| 4691 | 23703573 | Finally, we revealed that Ex-4 and GLP-1 significantly elevated insulin secretion via upregulation of the BTG2-PDX-1 axis in pancreatic islets, and this phenomenon was abolished by endogenous BTG2 knockdown. |
| 4692 | 23703573 | Collectively, our current study provides a novel molecular mechanism by which GLP-1 positively regulates insulin gene expression via BTG2, suggesting that BTG2 has a key function in insulin secretion in pancreatic β-cells. |
| 4693 | 23703573 | B-cell translocation gene 2 positively regulates GLP-1-stimulated insulin secretion via induction of PDX-1 in pancreatic β-cells. |
| 4694 | 23703573 | Here we demonstrate that B-cell translocation gene 2 (BTG2) is a crucial regulator in GLP-1-induced insulin gene expression and insulin secretion via upregulation of pancreatic duodenal homeobox-1 (PDX-1) in pancreatic β-cells. |
| 4695 | 23703573 | GLP-1 treatment significantly increased BTG2, PDX-1 and insulin gene expression in pancreatic β-cells. |
| 4696 | 23703573 | Notably, adenovirus-mediated overexpression of BTG2 significantly elevated insulin secretion, as well as insulin and PDX-1 gene expression. |
| 4697 | 23703573 | Physical interaction studies showed that BTG2 is associated with increased PDX-1 occupancy on the insulin gene promoter via a direct interaction with PDX-1. |
| 4698 | 23703573 | Exendin-4 (Ex-4), a GLP-1 agonist, and GLP-1 in pancreatic β-cells increased insulin secretion through the BTG2-PDX-1-insulin pathway, which was blocked by endogenous BTG2 knockdown using a BTG2 small interfering RNA knockdown system. |
| 4699 | 23703573 | Finally, we revealed that Ex-4 and GLP-1 significantly elevated insulin secretion via upregulation of the BTG2-PDX-1 axis in pancreatic islets, and this phenomenon was abolished by endogenous BTG2 knockdown. |
| 4700 | 23703573 | Collectively, our current study provides a novel molecular mechanism by which GLP-1 positively regulates insulin gene expression via BTG2, suggesting that BTG2 has a key function in insulin secretion in pancreatic β-cells. |
| 4701 | 23703573 | B-cell translocation gene 2 positively regulates GLP-1-stimulated insulin secretion via induction of PDX-1 in pancreatic β-cells. |
| 4702 | 23703573 | Here we demonstrate that B-cell translocation gene 2 (BTG2) is a crucial regulator in GLP-1-induced insulin gene expression and insulin secretion via upregulation of pancreatic duodenal homeobox-1 (PDX-1) in pancreatic β-cells. |
| 4703 | 23703573 | GLP-1 treatment significantly increased BTG2, PDX-1 and insulin gene expression in pancreatic β-cells. |
| 4704 | 23703573 | Notably, adenovirus-mediated overexpression of BTG2 significantly elevated insulin secretion, as well as insulin and PDX-1 gene expression. |
| 4705 | 23703573 | Physical interaction studies showed that BTG2 is associated with increased PDX-1 occupancy on the insulin gene promoter via a direct interaction with PDX-1. |
| 4706 | 23703573 | Exendin-4 (Ex-4), a GLP-1 agonist, and GLP-1 in pancreatic β-cells increased insulin secretion through the BTG2-PDX-1-insulin pathway, which was blocked by endogenous BTG2 knockdown using a BTG2 small interfering RNA knockdown system. |
| 4707 | 23703573 | Finally, we revealed that Ex-4 and GLP-1 significantly elevated insulin secretion via upregulation of the BTG2-PDX-1 axis in pancreatic islets, and this phenomenon was abolished by endogenous BTG2 knockdown. |
| 4708 | 23703573 | Collectively, our current study provides a novel molecular mechanism by which GLP-1 positively regulates insulin gene expression via BTG2, suggesting that BTG2 has a key function in insulin secretion in pancreatic β-cells. |
| 4709 | 23703573 | B-cell translocation gene 2 positively regulates GLP-1-stimulated insulin secretion via induction of PDX-1 in pancreatic β-cells. |
| 4710 | 23703573 | Here we demonstrate that B-cell translocation gene 2 (BTG2) is a crucial regulator in GLP-1-induced insulin gene expression and insulin secretion via upregulation of pancreatic duodenal homeobox-1 (PDX-1) in pancreatic β-cells. |
| 4711 | 23703573 | GLP-1 treatment significantly increased BTG2, PDX-1 and insulin gene expression in pancreatic β-cells. |
| 4712 | 23703573 | Notably, adenovirus-mediated overexpression of BTG2 significantly elevated insulin secretion, as well as insulin and PDX-1 gene expression. |
| 4713 | 23703573 | Physical interaction studies showed that BTG2 is associated with increased PDX-1 occupancy on the insulin gene promoter via a direct interaction with PDX-1. |
| 4714 | 23703573 | Exendin-4 (Ex-4), a GLP-1 agonist, and GLP-1 in pancreatic β-cells increased insulin secretion through the BTG2-PDX-1-insulin pathway, which was blocked by endogenous BTG2 knockdown using a BTG2 small interfering RNA knockdown system. |
| 4715 | 23703573 | Finally, we revealed that Ex-4 and GLP-1 significantly elevated insulin secretion via upregulation of the BTG2-PDX-1 axis in pancreatic islets, and this phenomenon was abolished by endogenous BTG2 knockdown. |
| 4716 | 23703573 | Collectively, our current study provides a novel molecular mechanism by which GLP-1 positively regulates insulin gene expression via BTG2, suggesting that BTG2 has a key function in insulin secretion in pancreatic β-cells. |
| 4717 | 23703573 | B-cell translocation gene 2 positively regulates GLP-1-stimulated insulin secretion via induction of PDX-1 in pancreatic β-cells. |
| 4718 | 23703573 | Here we demonstrate that B-cell translocation gene 2 (BTG2) is a crucial regulator in GLP-1-induced insulin gene expression and insulin secretion via upregulation of pancreatic duodenal homeobox-1 (PDX-1) in pancreatic β-cells. |
| 4719 | 23703573 | GLP-1 treatment significantly increased BTG2, PDX-1 and insulin gene expression in pancreatic β-cells. |
| 4720 | 23703573 | Notably, adenovirus-mediated overexpression of BTG2 significantly elevated insulin secretion, as well as insulin and PDX-1 gene expression. |
| 4721 | 23703573 | Physical interaction studies showed that BTG2 is associated with increased PDX-1 occupancy on the insulin gene promoter via a direct interaction with PDX-1. |
| 4722 | 23703573 | Exendin-4 (Ex-4), a GLP-1 agonist, and GLP-1 in pancreatic β-cells increased insulin secretion through the BTG2-PDX-1-insulin pathway, which was blocked by endogenous BTG2 knockdown using a BTG2 small interfering RNA knockdown system. |
| 4723 | 23703573 | Finally, we revealed that Ex-4 and GLP-1 significantly elevated insulin secretion via upregulation of the BTG2-PDX-1 axis in pancreatic islets, and this phenomenon was abolished by endogenous BTG2 knockdown. |
| 4724 | 23703573 | Collectively, our current study provides a novel molecular mechanism by which GLP-1 positively regulates insulin gene expression via BTG2, suggesting that BTG2 has a key function in insulin secretion in pancreatic β-cells. |
| 4725 | 23703573 | B-cell translocation gene 2 positively regulates GLP-1-stimulated insulin secretion via induction of PDX-1 in pancreatic β-cells. |
| 4726 | 23703573 | Here we demonstrate that B-cell translocation gene 2 (BTG2) is a crucial regulator in GLP-1-induced insulin gene expression and insulin secretion via upregulation of pancreatic duodenal homeobox-1 (PDX-1) in pancreatic β-cells. |
| 4727 | 23703573 | GLP-1 treatment significantly increased BTG2, PDX-1 and insulin gene expression in pancreatic β-cells. |
| 4728 | 23703573 | Notably, adenovirus-mediated overexpression of BTG2 significantly elevated insulin secretion, as well as insulin and PDX-1 gene expression. |
| 4729 | 23703573 | Physical interaction studies showed that BTG2 is associated with increased PDX-1 occupancy on the insulin gene promoter via a direct interaction with PDX-1. |
| 4730 | 23703573 | Exendin-4 (Ex-4), a GLP-1 agonist, and GLP-1 in pancreatic β-cells increased insulin secretion through the BTG2-PDX-1-insulin pathway, which was blocked by endogenous BTG2 knockdown using a BTG2 small interfering RNA knockdown system. |
| 4731 | 23703573 | Finally, we revealed that Ex-4 and GLP-1 significantly elevated insulin secretion via upregulation of the BTG2-PDX-1 axis in pancreatic islets, and this phenomenon was abolished by endogenous BTG2 knockdown. |
| 4732 | 23703573 | Collectively, our current study provides a novel molecular mechanism by which GLP-1 positively regulates insulin gene expression via BTG2, suggesting that BTG2 has a key function in insulin secretion in pancreatic β-cells. |
| 4733 | 23724162 | Type 1 diabetes mellitus (T1DM) is characterized by recognition of beta cell proteins as self-antigens, called autoantigens (AAgs), by patients' own CD4+ and CD8+ T cells and/or the products of self-reactive B cells, called autoantibodies. |
| 4734 | 23724162 | Since many excellent reviews have covered the previously identified T1DM-associated AAgs exhaustedly, here we only focus on several recently discovered T1DM-AAgs (PDX1, ZnT8, CHGA, and IAAP). |
| 4735 | 23725211 | Significant expressions of PDX1, neurogenin3 (Ngn3), glucagon, glucose transporter2 (Glut2), and somatostatin were detected by quantitative RT-PCR (P < 0.05). |
| 4736 | 23725211 | PDX1 and insulin proteins were shown by immunocytochemistry analysis. |
| 4737 | 23725211 | Insulin secretion of hUDSCs(PDX1+) in the high-glucose medium was 1.8 μU/mL. |
| 4738 | 23725211 | Significant expressions of PDX1, neurogenin3 (Ngn3), glucagon, glucose transporter2 (Glut2), and somatostatin were detected by quantitative RT-PCR (P < 0.05). |
| 4739 | 23725211 | PDX1 and insulin proteins were shown by immunocytochemistry analysis. |
| 4740 | 23725211 | Insulin secretion of hUDSCs(PDX1+) in the high-glucose medium was 1.8 μU/mL. |
| 4741 | 23725211 | Significant expressions of PDX1, neurogenin3 (Ngn3), glucagon, glucose transporter2 (Glut2), and somatostatin were detected by quantitative RT-PCR (P < 0.05). |
| 4742 | 23725211 | PDX1 and insulin proteins were shown by immunocytochemistry analysis. |
| 4743 | 23725211 | Insulin secretion of hUDSCs(PDX1+) in the high-glucose medium was 1.8 μU/mL. |
| 4744 | 23736775 | A Short-activating RNA Oligonucleotide Targeting the Islet β-cell Transcriptional Factor MafA in CD34(+) Cells. |
| 4745 | 23736775 | We have developed a novel approach using short-activating RNA oligonucleotides to differentiate adult human CD34(+) cells into insulin-secreting cells. |
| 4746 | 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. |
| 4747 | 23736775 | These included Pancreatic and duodenal homeobox gene-1 (PDX1), Neurogenin 3, NeuroD, and NK6 homeobox 1 (NKx6-1). |
| 4748 | 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. |
| 4749 | 23737644 | After evaluation of oxidative stress, we determined the expression and subcellular localization of proteins involved in maintaining redox balance and insulin gene expression, such as nuclear factor erythroid-derived 2 (Nrf2), glutathione reductase, PDX-1, and MafA. |
| 4750 | 23737644 | Furthermore, GS reduced ability of PDX-1 and MafA to bind DNA. |
| 4751 | 23737644 | After evaluation of oxidative stress, we determined the expression and subcellular localization of proteins involved in maintaining redox balance and insulin gene expression, such as nuclear factor erythroid-derived 2 (Nrf2), glutathione reductase, PDX-1, and MafA. |
| 4752 | 23737644 | Furthermore, GS reduced ability of PDX-1 and MafA to bind DNA. |
| 4753 | 23750005 | Directed differentiation of IM and WB cells by Pdx1-Ngn3-MafA (PNM) into pancreatic beta-like cells revealed that the IM cells are more susceptible to directed beta cell differentiation because of their open chromatin configuration, as demonstrated by expression of key pancreatic beta cell genes, secretion of insulin in response to glucose stimulation, and easy access to exogenous PNM proteins at the rat insulin 1 and Pdx1 promoters. |
| 4754 | 23750005 | This notion that IM cells are superior to their parental cells is further supported by the epigenetic demonstration of accessibility of Pdx1 and insulin 1 promoters. |
| 4755 | 23750005 | Directed differentiation of IM and WB cells by Pdx1-Ngn3-MafA (PNM) into pancreatic beta-like cells revealed that the IM cells are more susceptible to directed beta cell differentiation because of their open chromatin configuration, as demonstrated by expression of key pancreatic beta cell genes, secretion of insulin in response to glucose stimulation, and easy access to exogenous PNM proteins at the rat insulin 1 and Pdx1 promoters. |
| 4756 | 23750005 | This notion that IM cells are superior to their parental cells is further supported by the epigenetic demonstration of accessibility of Pdx1 and insulin 1 promoters. |
| 4757 | 23756944 | Here we describe a new approach for the generation of glucose responsive IPCs using ES cells ectopically expressing pancreatic and duodenal homeobox 1 (Pdx1) and paired box gene 4 (Pax4). |
| 4758 | 23769060 | Additionally, some endocrine transdifferentiation of the liver, with storage of insulin in granules, and expression of some β-cell transcription factors (eg, Pdx1, Neurod1, Neurog3, Nkx2-2, Pax4) and pancreatic hormones in both studies. |
| 4759 | 23769060 | Reverse-transcription polymerase chain reaction analysis of the liver tissue revealed expression of several β-cell transcription factors, including the key factors, Pdx-1 and Neurod1, pancreatic hormones, glucagon, and somatostatin; however, endogenous pig insulin was not expressed. |
| 4760 | 23769060 | Additionally, some endocrine transdifferentiation of the liver, with storage of insulin in granules, and expression of some β-cell transcription factors (eg, Pdx1, Neurod1, Neurog3, Nkx2-2, Pax4) and pancreatic hormones in both studies. |
| 4761 | 23769060 | Reverse-transcription polymerase chain reaction analysis of the liver tissue revealed expression of several β-cell transcription factors, including the key factors, Pdx-1 and Neurod1, pancreatic hormones, glucagon, and somatostatin; however, endogenous pig insulin was not expressed. |
| 4762 | 23775765 | Pancreatic duodenal homeobox-1 (Pdx1), a transcription factor required for pancreatic development and maintenance of β-cell function, was assessed for a possible role in postnatal β-cell formation from progenitors in the pancreatic ducts by selectively deleting Pdx1 from the ducts. |
| 4763 | 23775765 | Carbonic anhydrase II (CAII)(Cre);Pdx1(Fl) mice were euglycemic for the first 2 postnatal weeks but showed moderate hyperglycemia from 3 to 7 weeks of age. |
| 4764 | 23775765 | Within the same pancreas, there was a mixed population of islets, with PDX1 and MAFA protein expression normal in some cells and severely diminished in others. |
| 4765 | 23775765 | Pancreatic duodenal homeobox-1 (Pdx1), a transcription factor required for pancreatic development and maintenance of β-cell function, was assessed for a possible role in postnatal β-cell formation from progenitors in the pancreatic ducts by selectively deleting Pdx1 from the ducts. |
| 4766 | 23775765 | Carbonic anhydrase II (CAII)(Cre);Pdx1(Fl) mice were euglycemic for the first 2 postnatal weeks but showed moderate hyperglycemia from 3 to 7 weeks of age. |
| 4767 | 23775765 | Within the same pancreas, there was a mixed population of islets, with PDX1 and MAFA protein expression normal in some cells and severely diminished in others. |
| 4768 | 23775765 | Pancreatic duodenal homeobox-1 (Pdx1), a transcription factor required for pancreatic development and maintenance of β-cell function, was assessed for a possible role in postnatal β-cell formation from progenitors in the pancreatic ducts by selectively deleting Pdx1 from the ducts. |
| 4769 | 23775765 | Carbonic anhydrase II (CAII)(Cre);Pdx1(Fl) mice were euglycemic for the first 2 postnatal weeks but showed moderate hyperglycemia from 3 to 7 weeks of age. |
| 4770 | 23775765 | Within the same pancreas, there was a mixed population of islets, with PDX1 and MAFA protein expression normal in some cells and severely diminished in others. |
| 4771 | 23788637 | We have used in vitro and in vivo systems to show that FoxO1, an integrator of metabolic stimuli, inhibits PPARγ expression in β-cells, thus transcription of its target genes (Pdx1, glucose-dependent insulinotropic polypeptide (GIP) receptor, and pyruvate carboxylase) that are important regulators of β-cell function, survival, and compensation. |
| 4772 | 23796517 | Thermodynamic and structural determinants of differential Pdx1 binding to elements from the insulin and IAPP promoters. |
| 4773 | 23796517 | In adult mammals, the production of insulin and other peptide hormones, such as the islet amyloid polypeptide (IAPP), is limited to β-cells due to tissue-specific expression of a set of transcription factors, the best known of which is pancreatic duodenal homeobox protein 1 (Pdx1). |
| 4774 | 23796517 | Strikingly, while Pdx1 responsive elements in the human insulin promoter conform to the pentanucleotide 5'-CTAAT-3' sequence, the Pdx1 responsive elements in the human iapp promoter all contain a substitution to 5'-TTAAT-3'. |
| 4775 | 23796517 | Taken together, our results suggest a molecular mechanism for differential Pdx1 affinity to elements from the insulin and iapp promoter sequences. |
| 4776 | 23796517 | Thermodynamic and structural determinants of differential Pdx1 binding to elements from the insulin and IAPP promoters. |
| 4777 | 23796517 | In adult mammals, the production of insulin and other peptide hormones, such as the islet amyloid polypeptide (IAPP), is limited to β-cells due to tissue-specific expression of a set of transcription factors, the best known of which is pancreatic duodenal homeobox protein 1 (Pdx1). |
| 4778 | 23796517 | Strikingly, while Pdx1 responsive elements in the human insulin promoter conform to the pentanucleotide 5'-CTAAT-3' sequence, the Pdx1 responsive elements in the human iapp promoter all contain a substitution to 5'-TTAAT-3'. |
| 4779 | 23796517 | Taken together, our results suggest a molecular mechanism for differential Pdx1 affinity to elements from the insulin and iapp promoter sequences. |
| 4780 | 23796517 | Thermodynamic and structural determinants of differential Pdx1 binding to elements from the insulin and IAPP promoters. |
| 4781 | 23796517 | In adult mammals, the production of insulin and other peptide hormones, such as the islet amyloid polypeptide (IAPP), is limited to β-cells due to tissue-specific expression of a set of transcription factors, the best known of which is pancreatic duodenal homeobox protein 1 (Pdx1). |
| 4782 | 23796517 | Strikingly, while Pdx1 responsive elements in the human insulin promoter conform to the pentanucleotide 5'-CTAAT-3' sequence, the Pdx1 responsive elements in the human iapp promoter all contain a substitution to 5'-TTAAT-3'. |
| 4783 | 23796517 | Taken together, our results suggest a molecular mechanism for differential Pdx1 affinity to elements from the insulin and iapp promoter sequences. |
| 4784 | 23796517 | Thermodynamic and structural determinants of differential Pdx1 binding to elements from the insulin and IAPP promoters. |
| 4785 | 23796517 | In adult mammals, the production of insulin and other peptide hormones, such as the islet amyloid polypeptide (IAPP), is limited to β-cells due to tissue-specific expression of a set of transcription factors, the best known of which is pancreatic duodenal homeobox protein 1 (Pdx1). |
| 4786 | 23796517 | Strikingly, while Pdx1 responsive elements in the human insulin promoter conform to the pentanucleotide 5'-CTAAT-3' sequence, the Pdx1 responsive elements in the human iapp promoter all contain a substitution to 5'-TTAAT-3'. |
| 4787 | 23796517 | Taken together, our results suggest a molecular mechanism for differential Pdx1 affinity to elements from the insulin and iapp promoter sequences. |
| 4788 | 23825225 | Previously, exchange protein directly activated by cAMP 2 (Epac2) and PKA were known to play a role in glucose-stimulated insulin secretion (GSIS) by pancreatic β cells. |
| 4789 | 23825225 | Interestingly, Epac1(-/-) mice also showed metabolic defects, including increased respiratory exchange ratio (RER) and plasma triglyceride (TG), and more severe diet-induced obesity with insulin resistance, which may contributed to β-cell dysfunction. |
| 4790 | 23825225 | However, islets differentiated from Epac1(-/-) ES cells showed insulin secretion defect, reduced Glut2 and PDX-1 expression, and abolished GLP-1-stimulated PCNA induction, suggesting a role of Epac1 in β-cell function. |
| 4791 | 23828045 | At 1 week after multiple low-dose STZ administrations, pancreatic β-cells showed impaired insulin expression, while maintaining expression of nuclear Nkx6.1. |
| 4792 | 23828045 | This was accompanied by significant upregulation of p53-responsive genes in islets, including a mediator of cell cycle arrest, p21 (also known as Waf1 and Cip1). |
| 4793 | 23828045 | STZ treatment also suppressed expression of a wide range of genes linked with key β-cell functions or diabetes development, such as G6pc2, Slc2a2 (Glut2), Slc30a8, Neurod1, Ucn3, Gad1, Isl1, Foxa2, Vdr, Pdx1, Fkbp1b and Abcc8, suggesting global β-cell defects in STZ-treated islets. |
| 4794 | 23828045 | When a pancreas-targeted adeno-associated virus (AAV) vector was employed for long-term Glp-1 gene delivery, pancreatic GLP-1 expression protected mice from STZ-induced diabetes through preservation of the β-cell mass. |
| 4795 | 23828045 | Upon pancreatic GLP-1 expression, upregulation of Cxcl13 and Nptx2 was observed in STZ-damaged islets, but not in untreated normal islets. |
| 4796 | 23828045 | Given the pro-β-cell-survival effects of Cxcl12 (Sdf-1) in inducing GLP-1 production in α-cells, pancreatic GLP-1-mediated Cxcl13 induction might also play a crucial role in maintaining the integrity of β-cells in damaged islets. |
| 4797 | 23831626 | In vitro generation of glucose-responsive insulin producing cells using lentiviral based pdx-1 gene transduction of mouse (C57BL/6) mesenchymal stem cells. |
| 4798 | 23831626 | Our results demonstrated that mouse mesenchymal stem cells can be differentiated into effective glucose-responsive insulin producing cells through our new recombinant lentiviral transduction of pdx-1 gene in vitro. |
| 4799 | 23831626 | In vitro generation of glucose-responsive insulin producing cells using lentiviral based pdx-1 gene transduction of mouse (C57BL/6) mesenchymal stem cells. |
| 4800 | 23831626 | Our results demonstrated that mouse mesenchymal stem cells can be differentiated into effective glucose-responsive insulin producing cells through our new recombinant lentiviral transduction of pdx-1 gene in vitro. |
| 4801 | 23847135 | We show that proximal (PBGs)-to-distal (PDGs) maturational lineages start near the duodenum with cells expressing markers of pluripotency (NANOG, OCT4, and SOX2), proliferation (Ki67), self-replication (SALL4), and early hepato-pancreatic commitment (SOX9, SOX17, PDX1, and LGR5), transitioning to PDG cells with no expression of pluripotency or self-replication markers, maintenance of pancreatic genes (PDX1), and expression of markers of pancreatic endocrine maturation (NGN3, MUC6, and insulin). |
| 4802 | 23853095 | In pancreatic β-cells, glucose induces the binding of the transcription factor pancreatic duodenal homeobox-1 (PDX-1) to the insulin gene promoter to activate insulin gene transcription. |
| 4803 | 23853095 | We previously showed that the serine/threonine Per-Arnt-Sim domain-containing kinase (PASK) regulates insulin gene transcription via PDX-1. |
| 4804 | 23853095 | In this study, we aimed to identify the role of PASK in the regulation of PDX-1 phosphorylation, protein expression, and stability in insulin-secreting cells and isolated rodent islets of Langerhans. |
| 4805 | 23853095 | We observed that glucose induces a decrease in overall PDX-1 serine phosphorylation and that overexpression of WT PASK mimics this effect. |
| 4806 | 23853095 | Overexpression of WT PASK or KD GSK3β protects PDX-1 from degradation and results in increased PDX-1 protein abundance. |
| 4807 | 23853095 | Conversely, overexpression of KD PASK blocks glucose-induction of PDX-1 protein. |
| 4808 | 23853095 | We conclude that PASK phosphorylates and inactivates GSK3β, thereby preventing PDX-1 serine phosphorylation and alleviating GSK3β-mediated PDX-1 protein degradation in pancreatic β-cells. |
| 4809 | 23853095 | In pancreatic β-cells, glucose induces the binding of the transcription factor pancreatic duodenal homeobox-1 (PDX-1) to the insulin gene promoter to activate insulin gene transcription. |
| 4810 | 23853095 | We previously showed that the serine/threonine Per-Arnt-Sim domain-containing kinase (PASK) regulates insulin gene transcription via PDX-1. |
| 4811 | 23853095 | In this study, we aimed to identify the role of PASK in the regulation of PDX-1 phosphorylation, protein expression, and stability in insulin-secreting cells and isolated rodent islets of Langerhans. |
| 4812 | 23853095 | We observed that glucose induces a decrease in overall PDX-1 serine phosphorylation and that overexpression of WT PASK mimics this effect. |
| 4813 | 23853095 | Overexpression of WT PASK or KD GSK3β protects PDX-1 from degradation and results in increased PDX-1 protein abundance. |
| 4814 | 23853095 | Conversely, overexpression of KD PASK blocks glucose-induction of PDX-1 protein. |
| 4815 | 23853095 | We conclude that PASK phosphorylates and inactivates GSK3β, thereby preventing PDX-1 serine phosphorylation and alleviating GSK3β-mediated PDX-1 protein degradation in pancreatic β-cells. |
| 4816 | 23853095 | In pancreatic β-cells, glucose induces the binding of the transcription factor pancreatic duodenal homeobox-1 (PDX-1) to the insulin gene promoter to activate insulin gene transcription. |
| 4817 | 23853095 | We previously showed that the serine/threonine Per-Arnt-Sim domain-containing kinase (PASK) regulates insulin gene transcription via PDX-1. |
| 4818 | 23853095 | In this study, we aimed to identify the role of PASK in the regulation of PDX-1 phosphorylation, protein expression, and stability in insulin-secreting cells and isolated rodent islets of Langerhans. |
| 4819 | 23853095 | We observed that glucose induces a decrease in overall PDX-1 serine phosphorylation and that overexpression of WT PASK mimics this effect. |
| 4820 | 23853095 | Overexpression of WT PASK or KD GSK3β protects PDX-1 from degradation and results in increased PDX-1 protein abundance. |
| 4821 | 23853095 | Conversely, overexpression of KD PASK blocks glucose-induction of PDX-1 protein. |
| 4822 | 23853095 | We conclude that PASK phosphorylates and inactivates GSK3β, thereby preventing PDX-1 serine phosphorylation and alleviating GSK3β-mediated PDX-1 protein degradation in pancreatic β-cells. |
| 4823 | 23853095 | In pancreatic β-cells, glucose induces the binding of the transcription factor pancreatic duodenal homeobox-1 (PDX-1) to the insulin gene promoter to activate insulin gene transcription. |
| 4824 | 23853095 | We previously showed that the serine/threonine Per-Arnt-Sim domain-containing kinase (PASK) regulates insulin gene transcription via PDX-1. |
| 4825 | 23853095 | In this study, we aimed to identify the role of PASK in the regulation of PDX-1 phosphorylation, protein expression, and stability in insulin-secreting cells and isolated rodent islets of Langerhans. |
| 4826 | 23853095 | We observed that glucose induces a decrease in overall PDX-1 serine phosphorylation and that overexpression of WT PASK mimics this effect. |
| 4827 | 23853095 | Overexpression of WT PASK or KD GSK3β protects PDX-1 from degradation and results in increased PDX-1 protein abundance. |
| 4828 | 23853095 | Conversely, overexpression of KD PASK blocks glucose-induction of PDX-1 protein. |
| 4829 | 23853095 | We conclude that PASK phosphorylates and inactivates GSK3β, thereby preventing PDX-1 serine phosphorylation and alleviating GSK3β-mediated PDX-1 protein degradation in pancreatic β-cells. |
| 4830 | 23853095 | In pancreatic β-cells, glucose induces the binding of the transcription factor pancreatic duodenal homeobox-1 (PDX-1) to the insulin gene promoter to activate insulin gene transcription. |
| 4831 | 23853095 | We previously showed that the serine/threonine Per-Arnt-Sim domain-containing kinase (PASK) regulates insulin gene transcription via PDX-1. |
| 4832 | 23853095 | In this study, we aimed to identify the role of PASK in the regulation of PDX-1 phosphorylation, protein expression, and stability in insulin-secreting cells and isolated rodent islets of Langerhans. |
| 4833 | 23853095 | We observed that glucose induces a decrease in overall PDX-1 serine phosphorylation and that overexpression of WT PASK mimics this effect. |
| 4834 | 23853095 | Overexpression of WT PASK or KD GSK3β protects PDX-1 from degradation and results in increased PDX-1 protein abundance. |
| 4835 | 23853095 | Conversely, overexpression of KD PASK blocks glucose-induction of PDX-1 protein. |
| 4836 | 23853095 | We conclude that PASK phosphorylates and inactivates GSK3β, thereby preventing PDX-1 serine phosphorylation and alleviating GSK3β-mediated PDX-1 protein degradation in pancreatic β-cells. |
| 4837 | 23853095 | In pancreatic β-cells, glucose induces the binding of the transcription factor pancreatic duodenal homeobox-1 (PDX-1) to the insulin gene promoter to activate insulin gene transcription. |
| 4838 | 23853095 | We previously showed that the serine/threonine Per-Arnt-Sim domain-containing kinase (PASK) regulates insulin gene transcription via PDX-1. |
| 4839 | 23853095 | In this study, we aimed to identify the role of PASK in the regulation of PDX-1 phosphorylation, protein expression, and stability in insulin-secreting cells and isolated rodent islets of Langerhans. |
| 4840 | 23853095 | We observed that glucose induces a decrease in overall PDX-1 serine phosphorylation and that overexpression of WT PASK mimics this effect. |
| 4841 | 23853095 | Overexpression of WT PASK or KD GSK3β protects PDX-1 from degradation and results in increased PDX-1 protein abundance. |
| 4842 | 23853095 | Conversely, overexpression of KD PASK blocks glucose-induction of PDX-1 protein. |
| 4843 | 23853095 | We conclude that PASK phosphorylates and inactivates GSK3β, thereby preventing PDX-1 serine phosphorylation and alleviating GSK3β-mediated PDX-1 protein degradation in pancreatic β-cells. |
| 4844 | 23853095 | In pancreatic β-cells, glucose induces the binding of the transcription factor pancreatic duodenal homeobox-1 (PDX-1) to the insulin gene promoter to activate insulin gene transcription. |
| 4845 | 23853095 | We previously showed that the serine/threonine Per-Arnt-Sim domain-containing kinase (PASK) regulates insulin gene transcription via PDX-1. |
| 4846 | 23853095 | In this study, we aimed to identify the role of PASK in the regulation of PDX-1 phosphorylation, protein expression, and stability in insulin-secreting cells and isolated rodent islets of Langerhans. |
| 4847 | 23853095 | We observed that glucose induces a decrease in overall PDX-1 serine phosphorylation and that overexpression of WT PASK mimics this effect. |
| 4848 | 23853095 | Overexpression of WT PASK or KD GSK3β protects PDX-1 from degradation and results in increased PDX-1 protein abundance. |
| 4849 | 23853095 | Conversely, overexpression of KD PASK blocks glucose-induction of PDX-1 protein. |
| 4850 | 23853095 | We conclude that PASK phosphorylates and inactivates GSK3β, thereby preventing PDX-1 serine phosphorylation and alleviating GSK3β-mediated PDX-1 protein degradation in pancreatic β-cells. |
| 4851 | 23863625 | Hydrogen peroxide treatment of β cell lines induced cytoplasmic translocation of MAFA and NKX6.1. |
| 4852 | 23863625 | MAFA levels were reduced, followed by a reduction in NKX6.1 upon development of hyperglycemia in db/db mice, a T2DM model. |
| 4853 | 23863625 | Transgenic expression of the glutathione peroxidase-1 antioxidant enzyme (GPX1) in db/db islet β cells restored nuclear MAFA, nuclear NKX6.1, and β cell function in vivo. |
| 4854 | 23863625 | Notably, the selective decrease in MAFA, NKX6.1, and PDX1 expression was found in human T2DM islets. |
| 4855 | 23863625 | MAFB, a MAFA-related transcription factor expressed in human β cells, was also severely compromised. |
| 4856 | 23863625 | We propose that MAFA, MAFB, NKX6.1, and PDX1 activity provides a gauge of islet β cell function, with loss of MAFA (and/or MAFB) representing an early indicator of β cell inactivity and the subsequent deficit of more impactful NKX6.1 (and/or PDX1) resulting in overt dysfunction associated with T2DM. |
| 4857 | 23863625 | Hydrogen peroxide treatment of β cell lines induced cytoplasmic translocation of MAFA and NKX6.1. |
| 4858 | 23863625 | MAFA levels were reduced, followed by a reduction in NKX6.1 upon development of hyperglycemia in db/db mice, a T2DM model. |
| 4859 | 23863625 | Transgenic expression of the glutathione peroxidase-1 antioxidant enzyme (GPX1) in db/db islet β cells restored nuclear MAFA, nuclear NKX6.1, and β cell function in vivo. |
| 4860 | 23863625 | Notably, the selective decrease in MAFA, NKX6.1, and PDX1 expression was found in human T2DM islets. |
| 4861 | 23863625 | MAFB, a MAFA-related transcription factor expressed in human β cells, was also severely compromised. |
| 4862 | 23863625 | We propose that MAFA, MAFB, NKX6.1, and PDX1 activity provides a gauge of islet β cell function, with loss of MAFA (and/or MAFB) representing an early indicator of β cell inactivity and the subsequent deficit of more impactful NKX6.1 (and/or PDX1) resulting in overt dysfunction associated with T2DM. |
| 4863 | 23884882 | HFS diets also resulted in decreased expression of essential β-cell transcription factors forkhead box O1 (FOXO1), NKX6-1, NKX2-2, and PDX1, which did not occur with resveratrol supplementation. |
| 4864 | 23897760 | Enrichment of human embryonic stem cell-derived NKX6.1-expressing pancreatic progenitor cells accelerates the maturation of insulin-secreting cells in vivo. |
| 4865 | 23897760 | We previously described a differentiation protocol to generate pancreatic progenitor cells from hESCs, composed of mainly pancreatic endoderm (PDX1/NKX6.1-positive), endocrine precursors (NKX2.2/synaptophysin-positive, hormone/NKX6.1-negative), and polyhormonal cells (insulin/glucagon-positive, NKX6.1-negative). |
| 4866 | 23897760 | However, the relative contributions of NKX6.1-negative versus NKX6.1-positive cell fractions to the maturation of functional β-cells remained unclear. |
| 4867 | 23897760 | Prior to transplant, both populations contained a high proportion of PDX1-expressing cells (~85%-90%) but were distinguished by their relatively high (~80%) or low (~25%) expression of NKX6.1. |
| 4868 | 23897760 | Fasting human C-peptide levels were similar between groups throughout the study, but only NKX6.1-high grafts displayed robust meal-, glucose- and arginine-responsive insulin secretion as early as 3 months post-transplant. |
| 4869 | 23897760 | Theracyte devices from both groups contained almost exclusively pancreatic endocrine tissue, but NKX6.1-high grafts contained a greater proportion of insulin-positive and somatostatin-positive cells, whereas NKX6.1-low grafts contained mainly glucagon-expressing cells. |
| 4870 | 23897760 | Insulin-positive cells in NKX6.1-high, but not NKX6.1-low grafts expressed nuclear MAFA. |
| 4871 | 23897760 | Enrichment of human embryonic stem cell-derived NKX6.1-expressing pancreatic progenitor cells accelerates the maturation of insulin-secreting cells in vivo. |
| 4872 | 23897760 | We previously described a differentiation protocol to generate pancreatic progenitor cells from hESCs, composed of mainly pancreatic endoderm (PDX1/NKX6.1-positive), endocrine precursors (NKX2.2/synaptophysin-positive, hormone/NKX6.1-negative), and polyhormonal cells (insulin/glucagon-positive, NKX6.1-negative). |
| 4873 | 23897760 | However, the relative contributions of NKX6.1-negative versus NKX6.1-positive cell fractions to the maturation of functional β-cells remained unclear. |
| 4874 | 23897760 | Prior to transplant, both populations contained a high proportion of PDX1-expressing cells (~85%-90%) but were distinguished by their relatively high (~80%) or low (~25%) expression of NKX6.1. |
| 4875 | 23897760 | Fasting human C-peptide levels were similar between groups throughout the study, but only NKX6.1-high grafts displayed robust meal-, glucose- and arginine-responsive insulin secretion as early as 3 months post-transplant. |
| 4876 | 23897760 | Theracyte devices from both groups contained almost exclusively pancreatic endocrine tissue, but NKX6.1-high grafts contained a greater proportion of insulin-positive and somatostatin-positive cells, whereas NKX6.1-low grafts contained mainly glucagon-expressing cells. |
| 4877 | 23897760 | Insulin-positive cells in NKX6.1-high, but not NKX6.1-low grafts expressed nuclear MAFA. |
| 4878 | 23897763 | In addition, the dynamic expression profile of endodermal marker Foxa2 and endocrine-specific genes, including HNF4α, Pdx1, Pax6, Nkx6.1, Glut2 and insulin, were detected by quantitative real-time PCR. |
| 4879 | 23927931 | The Krüppel-like protein Gli-similar 3 (Glis3) functions as a key regulator of insulin transcription. |
| 4880 | 23927931 | Recently, the Krüppel-like transcription factor, Gli-similar 3 (Glis3), was shown to bind the insulin (INS) promoter and positively influence insulin transcription. |
| 4881 | 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). |
| 4882 | 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. |
| 4883 | 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. |
| 4884 | 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. |
| 4885 | 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. |
| 4886 | 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. |
| 4887 | 23927931 | The Krüppel-like protein Gli-similar 3 (Glis3) functions as a key regulator of insulin transcription. |
| 4888 | 23927931 | Recently, the Krüppel-like transcription factor, Gli-similar 3 (Glis3), was shown to bind the insulin (INS) promoter and positively influence insulin transcription. |
| 4889 | 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). |
| 4890 | 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. |
| 4891 | 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. |
| 4892 | 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. |
| 4893 | 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. |
| 4894 | 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. |
| 4895 | 23927931 | The Krüppel-like protein Gli-similar 3 (Glis3) functions as a key regulator of insulin transcription. |
| 4896 | 23927931 | Recently, the Krüppel-like transcription factor, Gli-similar 3 (Glis3), was shown to bind the insulin (INS) promoter and positively influence insulin transcription. |
| 4897 | 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). |
| 4898 | 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. |
| 4899 | 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. |
| 4900 | 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. |
| 4901 | 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. |
| 4902 | 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. |
| 4903 | 23927931 | The Krüppel-like protein Gli-similar 3 (Glis3) functions as a key regulator of insulin transcription. |
| 4904 | 23927931 | Recently, the Krüppel-like transcription factor, Gli-similar 3 (Glis3), was shown to bind the insulin (INS) promoter and positively influence insulin transcription. |
| 4905 | 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). |
| 4906 | 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. |
| 4907 | 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. |
| 4908 | 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. |
| 4909 | 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. |
| 4910 | 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. |
| 4911 | 23927931 | The Krüppel-like protein Gli-similar 3 (Glis3) functions as a key regulator of insulin transcription. |
| 4912 | 23927931 | Recently, the Krüppel-like transcription factor, Gli-similar 3 (Glis3), was shown to bind the insulin (INS) promoter and positively influence insulin transcription. |
| 4913 | 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). |
| 4914 | 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. |
| 4915 | 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. |
| 4916 | 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. |
| 4917 | 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. |
| 4918 | 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. |
| 4919 | 23976832 | There are undifferentiated transcriptional progenitors Pdx1+/Ptf1a+/Cpa1+ tracking the growth of acini, ducts, α and β-islet cells. |
| 4920 | 23976832 | The upregulated transcriptional factors Pdx1 and ngn3 specify consequences of cell cycle regulation in early gut endocrine cells. |
| 4921 | 23976832 | The undifferentiated transcriptional factors basic helix loop helix (bHLH) protein regulate Ptf1a+/Cpa1+ in acini, ducts and it also regulate ngn3 to decrease expression of insulin and other pancreas secretions. |
| 4922 | 23976832 | There are undifferentiated transcriptional progenitors Pdx1+/Ptf1a+/Cpa1+ tracking the growth of acini, ducts, α and β-islet cells. |
| 4923 | 23976832 | The upregulated transcriptional factors Pdx1 and ngn3 specify consequences of cell cycle regulation in early gut endocrine cells. |
| 4924 | 23976832 | The undifferentiated transcriptional factors basic helix loop helix (bHLH) protein regulate Ptf1a+/Cpa1+ in acini, ducts and it also regulate ngn3 to decrease expression of insulin and other pancreas secretions. |
| 4925 | 21464101 | Primary islet cells primed with or without PLP (5 mmol/L) were treated with STZ (2 mmol/L) and were measured for cell viability, insulin secretion, free radicals and mRNA of Insulin and Pdx1. |
| 4926 | 21464101 | The specificity of PLP's response on insulin secretion was assessed with amino oxy acetic acid (AOAA)-PLP inhibitor. |
| 4927 | 21464101 | On 7, 14 and 21 d of STZ treatment, physiological parameters, islet morphology, insulin:glucagon, insulin:HSP104, and mRNA of Insulin, Glut2, Pdx1 and Reg1 were determined. |
| 4928 | 21464101 | In vitro, PLP protected islets against STZ-induced changes in viability, insulin secretion, prevented increase in free radical levels and normalized mRNA of Insulin and Pdx1. |
| 4929 | 21464101 | Further, AOAA inhibited PLP-induced insulin secretion in islets. |
| 4930 | 21464101 | Also, islet morphology, insulin:glucagon, insulin:HSP104 and mRNA levels of Insulin, Pdx1 and Glut2 were restored by 21 d. |
| 4931 | 21464101 | Primary islet cells primed with or without PLP (5 mmol/L) were treated with STZ (2 mmol/L) and were measured for cell viability, insulin secretion, free radicals and mRNA of Insulin and Pdx1. |
| 4932 | 21464101 | The specificity of PLP's response on insulin secretion was assessed with amino oxy acetic acid (AOAA)-PLP inhibitor. |
| 4933 | 21464101 | On 7, 14 and 21 d of STZ treatment, physiological parameters, islet morphology, insulin:glucagon, insulin:HSP104, and mRNA of Insulin, Glut2, Pdx1 and Reg1 were determined. |
| 4934 | 21464101 | In vitro, PLP protected islets against STZ-induced changes in viability, insulin secretion, prevented increase in free radical levels and normalized mRNA of Insulin and Pdx1. |
| 4935 | 21464101 | Further, AOAA inhibited PLP-induced insulin secretion in islets. |
| 4936 | 21464101 | Also, islet morphology, insulin:glucagon, insulin:HSP104 and mRNA levels of Insulin, Pdx1 and Glut2 were restored by 21 d. |