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Gene Information
Gene symbol: FOXA2
Gene name: forkhead box A2
HGNC ID: 5022
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 9685261 | Mutations in HNF-1alphaand HNF-4alpha genes impair insulin secretion and cause type 2 diabetes. |
| 2 | 9685261 | Regulation of HNF-4/HNF-1 expression by HNF-3alpha and HNF-3beta was studied in embryoid bodies in which one or both HNF-3alpha or HNF-3beta alleles were inactivated. |
| 3 | 9685261 | HNF-3beta positively regulated the expression of HNF-4alpha/HNF-1alpha and their downstream targets, implicating a role in diabetes. |
| 4 | 9685261 | In contrast, HNF-3alpha acts as a negative regulator of HNF-4alpha/HNF-1alpha demonstrating that HNF-3alpha and HNF-3beta have antagonistic transcriptional regulatory functions in vivo. |
| 5 | 9685261 | In addition, the HNF-3alpha/HNF-3beta ratio is modulated by the presence of insulin, providing evidence that the HNF network may have important roles in mediating the action of insulin. |
| 6 | 9685261 | Mutations in HNF-1alphaand HNF-4alpha genes impair insulin secretion and cause type 2 diabetes. |
| 7 | 9685261 | Regulation of HNF-4/HNF-1 expression by HNF-3alpha and HNF-3beta was studied in embryoid bodies in which one or both HNF-3alpha or HNF-3beta alleles were inactivated. |
| 8 | 9685261 | HNF-3beta positively regulated the expression of HNF-4alpha/HNF-1alpha and their downstream targets, implicating a role in diabetes. |
| 9 | 9685261 | In contrast, HNF-3alpha acts as a negative regulator of HNF-4alpha/HNF-1alpha demonstrating that HNF-3alpha and HNF-3beta have antagonistic transcriptional regulatory functions in vivo. |
| 10 | 9685261 | In addition, the HNF-3alpha/HNF-3beta ratio is modulated by the presence of insulin, providing evidence that the HNF network may have important roles in mediating the action of insulin. |
| 11 | 9685261 | Mutations in HNF-1alphaand HNF-4alpha genes impair insulin secretion and cause type 2 diabetes. |
| 12 | 9685261 | Regulation of HNF-4/HNF-1 expression by HNF-3alpha and HNF-3beta was studied in embryoid bodies in which one or both HNF-3alpha or HNF-3beta alleles were inactivated. |
| 13 | 9685261 | HNF-3beta positively regulated the expression of HNF-4alpha/HNF-1alpha and their downstream targets, implicating a role in diabetes. |
| 14 | 9685261 | In contrast, HNF-3alpha acts as a negative regulator of HNF-4alpha/HNF-1alpha demonstrating that HNF-3alpha and HNF-3beta have antagonistic transcriptional regulatory functions in vivo. |
| 15 | 9685261 | In addition, the HNF-3alpha/HNF-3beta ratio is modulated by the presence of insulin, providing evidence that the HNF network may have important roles in mediating the action of insulin. |
| 16 | 9685261 | Mutations in HNF-1alphaand HNF-4alpha genes impair insulin secretion and cause type 2 diabetes. |
| 17 | 9685261 | Regulation of HNF-4/HNF-1 expression by HNF-3alpha and HNF-3beta was studied in embryoid bodies in which one or both HNF-3alpha or HNF-3beta alleles were inactivated. |
| 18 | 9685261 | HNF-3beta positively regulated the expression of HNF-4alpha/HNF-1alpha and their downstream targets, implicating a role in diabetes. |
| 19 | 9685261 | In contrast, HNF-3alpha acts as a negative regulator of HNF-4alpha/HNF-1alpha demonstrating that HNF-3alpha and HNF-3beta have antagonistic transcriptional regulatory functions in vivo. |
| 20 | 9685261 | In addition, the HNF-3alpha/HNF-3beta ratio is modulated by the presence of insulin, providing evidence that the HNF network may have important roles in mediating the action of insulin. |
| 21 | 10748140 | DNase I footprinting and electrophoretic mobility shift assay indicated that site C contained one binding site for hepatocyte nuclear factor 1 (HNF1) and two binding sites for HNF3. |
| 22 | 10748140 | The mutations at positions +101 and +103, which are considered to be critical in binding HNF1 and HNF3, resulted in a 53% decrease in promoter activity, whereas the mutation of the proximal HNF3 binding site (+115 and +117) reduced promoter activity by 28%. |
| 23 | 10748140 | The mutations of these four sites resulted in marked decrease (70%) in promoter activity as well as diminished bindings of HNF1 and HNF3. |
| 24 | 10748140 | A to G mutation, which causes conversion of the HNF1 and HNF3 binding sequence to the NF-Y binding site, resulted in a 22% decrease in promoter activity. |
| 25 | 10748140 | We identified that both HNF1 and HNF3 function as transcriptional activators in GLUT2 gene expression. |
| 26 | 10748140 | Coexpression of the pGL+74 (+74 to +301) construct with the HNF1alpha and HNF3beta expression vectors in NIH 3T3 cells showed the synergistic effect on GLUT2 promoter activity compared with the expression of HNF1alpha, HNF3beta, or a combination of HNF1beta and HNF3beta. |
| 27 | 10748140 | These data suggest that HNF1alpha and HNF3beta may be the most important players in the tissue-specific expression of the human GLUT2 gene. |
| 28 | 10748140 | DNase I footprinting and electrophoretic mobility shift assay indicated that site C contained one binding site for hepatocyte nuclear factor 1 (HNF1) and two binding sites for HNF3. |
| 29 | 10748140 | The mutations at positions +101 and +103, which are considered to be critical in binding HNF1 and HNF3, resulted in a 53% decrease in promoter activity, whereas the mutation of the proximal HNF3 binding site (+115 and +117) reduced promoter activity by 28%. |
| 30 | 10748140 | The mutations of these four sites resulted in marked decrease (70%) in promoter activity as well as diminished bindings of HNF1 and HNF3. |
| 31 | 10748140 | A to G mutation, which causes conversion of the HNF1 and HNF3 binding sequence to the NF-Y binding site, resulted in a 22% decrease in promoter activity. |
| 32 | 10748140 | We identified that both HNF1 and HNF3 function as transcriptional activators in GLUT2 gene expression. |
| 33 | 10748140 | Coexpression of the pGL+74 (+74 to +301) construct with the HNF1alpha and HNF3beta expression vectors in NIH 3T3 cells showed the synergistic effect on GLUT2 promoter activity compared with the expression of HNF1alpha, HNF3beta, or a combination of HNF1beta and HNF3beta. |
| 34 | 10748140 | These data suggest that HNF1alpha and HNF3beta may be the most important players in the tissue-specific expression of the human GLUT2 gene. |
| 35 | 10799560 | Glucocorticoids stimulate gluconeogenesis by increasing the rate of transcription of genes that encode gluconeogenic enzymes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase. |
| 36 | 10799560 | Previous studies have shown that hepatic nuclear factor 3 (HNF3) is required as an accessory factor for several glucocorticoid-stimulated genes, including PEPCK. |
| 37 | 10799560 | Here, we show that adenovirus-mediated expression of an HNF3beta protein with a deleted C-terminal transactivation domain (HNF3betaDeltaC) reduces the glucocorticoid-induced expression of the PEPCK and glucose-6-phosphatase genes in H4IIE hepatoma cells. |
| 38 | 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). |
| 39 | 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. |
| 40 | 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. |
| 41 | 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. |
| 42 | 11018767 | Hepatocyte nuclear factor-3 (HNF-3) belongs to a large family of forkhead transcription factors and is made up of three members (HNF-3alpha, -3beta and -3gamma). |
| 43 | 11018767 | In attempting to explore the regulation of gene expression of HNF-3 members by physiological status, we analyzed the effects of insulin, dexamethasone and protein malnutrition on the hepatic mRNA level of each member. |
| 44 | 11018767 | The protein-free diet and gluten diet caused a 3. 7-fold increase in HNF-3g mRNA in the liver and did not affect the mRNA level of either HNF-3alpha or HNF-3beta. |
| 45 | 11018767 | Daily administration of dexamethasone caused the mRNA levels of HNF-3alpha and HNF-3beta to increase (2.3- and 1.4-fold, respectively), but had no effect on the HNF-3gamma mRNA level. |
| 46 | 11018767 | In diabetic rats that had been injected with streptozotocin, an elevation of the hepatic mRNA levels of HNF-3beta and HNF-3gamma was observed (1.6-and 1.9-fold, respectively). |
| 47 | 11018767 | HNF-3alpha mRNA was not affected by insulin status. |
| 48 | 11018767 | Hepatocyte nuclear factor-3 (HNF-3) belongs to a large family of forkhead transcription factors and is made up of three members (HNF-3alpha, -3beta and -3gamma). |
| 49 | 11018767 | In attempting to explore the regulation of gene expression of HNF-3 members by physiological status, we analyzed the effects of insulin, dexamethasone and protein malnutrition on the hepatic mRNA level of each member. |
| 50 | 11018767 | The protein-free diet and gluten diet caused a 3. 7-fold increase in HNF-3g mRNA in the liver and did not affect the mRNA level of either HNF-3alpha or HNF-3beta. |
| 51 | 11018767 | Daily administration of dexamethasone caused the mRNA levels of HNF-3alpha and HNF-3beta to increase (2.3- and 1.4-fold, respectively), but had no effect on the HNF-3gamma mRNA level. |
| 52 | 11018767 | In diabetic rats that had been injected with streptozotocin, an elevation of the hepatic mRNA levels of HNF-3beta and HNF-3gamma was observed (1.6-and 1.9-fold, respectively). |
| 53 | 11018767 | HNF-3alpha mRNA was not affected by insulin status. |
| 54 | 11018767 | Hepatocyte nuclear factor-3 (HNF-3) belongs to a large family of forkhead transcription factors and is made up of three members (HNF-3alpha, -3beta and -3gamma). |
| 55 | 11018767 | In attempting to explore the regulation of gene expression of HNF-3 members by physiological status, we analyzed the effects of insulin, dexamethasone and protein malnutrition on the hepatic mRNA level of each member. |
| 56 | 11018767 | The protein-free diet and gluten diet caused a 3. 7-fold increase in HNF-3g mRNA in the liver and did not affect the mRNA level of either HNF-3alpha or HNF-3beta. |
| 57 | 11018767 | Daily administration of dexamethasone caused the mRNA levels of HNF-3alpha and HNF-3beta to increase (2.3- and 1.4-fold, respectively), but had no effect on the HNF-3gamma mRNA level. |
| 58 | 11018767 | In diabetic rats that had been injected with streptozotocin, an elevation of the hepatic mRNA levels of HNF-3beta and HNF-3gamma was observed (1.6-and 1.9-fold, respectively). |
| 59 | 11018767 | HNF-3alpha mRNA was not affected by insulin status. |
| 60 | 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. |
| 61 | 11272196 | This comparison revealed three short conserved regions, designated PH1, PH2, and PH3. |
| 62 | 11272196 | We showed that HNF-3beta can bind and stimulate the activity of the human PH1 and PH2 elements in non-beta-cells. |
| 63 | 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. |
| 64 | 11272196 | Thus, it can be stated that at least some aspects of pdx-1 expression rely on the transcription factor HNF-3beta. |
| 65 | 11272196 | Because HNF-3beta is not restricted to beta-cells, the selective transcription of pdx-1 is likely to rely on additional factors. |
| 66 | 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. |
| 67 | 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. |
| 68 | 11272196 | This comparison revealed three short conserved regions, designated PH1, PH2, and PH3. |
| 69 | 11272196 | We showed that HNF-3beta can bind and stimulate the activity of the human PH1 and PH2 elements in non-beta-cells. |
| 70 | 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. |
| 71 | 11272196 | Thus, it can be stated that at least some aspects of pdx-1 expression rely on the transcription factor HNF-3beta. |
| 72 | 11272196 | Because HNF-3beta is not restricted to beta-cells, the selective transcription of pdx-1 is likely to rely on additional factors. |
| 73 | 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. |
| 74 | 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. |
| 75 | 11272196 | This comparison revealed three short conserved regions, designated PH1, PH2, and PH3. |
| 76 | 11272196 | We showed that HNF-3beta can bind and stimulate the activity of the human PH1 and PH2 elements in non-beta-cells. |
| 77 | 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. |
| 78 | 11272196 | Thus, it can be stated that at least some aspects of pdx-1 expression rely on the transcription factor HNF-3beta. |
| 79 | 11272196 | Because HNF-3beta is not restricted to beta-cells, the selective transcription of pdx-1 is likely to rely on additional factors. |
| 80 | 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. |
| 81 | 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. |
| 82 | 11272196 | This comparison revealed three short conserved regions, designated PH1, PH2, and PH3. |
| 83 | 11272196 | We showed that HNF-3beta can bind and stimulate the activity of the human PH1 and PH2 elements in non-beta-cells. |
| 84 | 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. |
| 85 | 11272196 | Thus, it can be stated that at least some aspects of pdx-1 expression rely on the transcription factor HNF-3beta. |
| 86 | 11272196 | Because HNF-3beta is not restricted to beta-cells, the selective transcription of pdx-1 is likely to rely on additional factors. |
| 87 | 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. |
| 88 | 11445544 | We have used conditional gene ablation to uncover a dramatic and unpredicted role for the winged-helix transcription factor Foxa2 (formerly HNF-3 beta) in pancreatic beta-cell differentiation and metabolism. |
| 89 | 11445544 | Mice that lack Foxa2 specifically in beta cells (Foxa2(loxP/loxP); Ins.Cre mice) are severely hypoglycemic and show dysregulated insulin secretion in response to both glucose and amino acids. |
| 90 | 11445544 | The Foxa2(loxP/loxP); Ins.Cre mice will serve as a unique model to investigate the regulation of insulin secretion by the beta cell and suggest the human FOXA2 as a candidate gene for familial hyperinsulinism. |
| 91 | 11445544 | We have used conditional gene ablation to uncover a dramatic and unpredicted role for the winged-helix transcription factor Foxa2 (formerly HNF-3 beta) in pancreatic beta-cell differentiation and metabolism. |
| 92 | 11445544 | Mice that lack Foxa2 specifically in beta cells (Foxa2(loxP/loxP); Ins.Cre mice) are severely hypoglycemic and show dysregulated insulin secretion in response to both glucose and amino acids. |
| 93 | 11445544 | The Foxa2(loxP/loxP); Ins.Cre mice will serve as a unique model to investigate the regulation of insulin secretion by the beta cell and suggest the human FOXA2 as a candidate gene for familial hyperinsulinism. |
| 94 | 11445544 | We have used conditional gene ablation to uncover a dramatic and unpredicted role for the winged-helix transcription factor Foxa2 (formerly HNF-3 beta) in pancreatic beta-cell differentiation and metabolism. |
| 95 | 11445544 | Mice that lack Foxa2 specifically in beta cells (Foxa2(loxP/loxP); Ins.Cre mice) are severely hypoglycemic and show dysregulated insulin secretion in response to both glucose and amino acids. |
| 96 | 11445544 | The Foxa2(loxP/loxP); Ins.Cre mice will serve as a unique model to investigate the regulation of insulin secretion by the beta cell and suggest the human FOXA2 as a candidate gene for familial hyperinsulinism. |
| 97 | 11904435 | Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. |
| 98 | 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. |
| 99 | 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(+/-). |
| 100 | 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(+/-)). |
| 101 | 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. |
| 102 | 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. |
| 103 | 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. |
| 104 | 11904435 | Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. |
| 105 | 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. |
| 106 | 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(+/-). |
| 107 | 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(+/-)). |
| 108 | 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. |
| 109 | 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. |
| 110 | 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. |
| 111 | 11904435 | Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. |
| 112 | 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. |
| 113 | 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(+/-). |
| 114 | 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(+/-)). |
| 115 | 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. |
| 116 | 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. |
| 117 | 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. |
| 118 | 11904435 | Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. |
| 119 | 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. |
| 120 | 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(+/-). |
| 121 | 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(+/-)). |
| 122 | 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. |
| 123 | 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. |
| 124 | 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. |
| 125 | 11904435 | Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. |
| 126 | 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. |
| 127 | 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(+/-). |
| 128 | 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(+/-)). |
| 129 | 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. |
| 130 | 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. |
| 131 | 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. |
| 132 | 11904435 | Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. |
| 133 | 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. |
| 134 | 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(+/-). |
| 135 | 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(+/-)). |
| 136 | 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. |
| 137 | 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. |
| 138 | 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. |
| 139 | 12000309 | Members of the Forkhead box a (Foxa) transcription factor family are expressed in the liver, pancreatic islets and intestine and both Foxa1 and Foxa2 regulate proglucagon gene transcription. |
| 140 | 12000309 | These findings identify Foxa3 as a member of the proglucagon gene G2 element binding-protein family that, unlike Foxa1, is not essential for control of islet or intestinal proglucagon gene expression in vivo. |
| 141 | 12124776 | Exendin-4 differentiation of a human pancreatic duct cell line into endocrine cells: involvement of PDX-1 and HNF3beta transcription factors. |
| 142 | 12124776 | Western blot analysis detected a progressive increase in protein levels of glucokinase and GLUT2 over 3 days of EX-4 treatment. |
| 143 | 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). |
| 144 | 12124776 | Double immunostaining showed that PDX-1 coexisted with insulin and glucagon in EX-4-treated cells. |
| 145 | 12124776 | EMSA results indicated that EX-4 caused a 12-fold increase in HNF3beta binding to PDX-1 promoter area II. |
| 146 | 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. |
| 147 | 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. |
| 148 | 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. |
| 149 | 12124776 | Exendin-4 differentiation of a human pancreatic duct cell line into endocrine cells: involvement of PDX-1 and HNF3beta transcription factors. |
| 150 | 12124776 | Western blot analysis detected a progressive increase in protein levels of glucokinase and GLUT2 over 3 days of EX-4 treatment. |
| 151 | 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). |
| 152 | 12124776 | Double immunostaining showed that PDX-1 coexisted with insulin and glucagon in EX-4-treated cells. |
| 153 | 12124776 | EMSA results indicated that EX-4 caused a 12-fold increase in HNF3beta binding to PDX-1 promoter area II. |
| 154 | 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. |
| 155 | 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. |
| 156 | 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. |
| 157 | 12124776 | Exendin-4 differentiation of a human pancreatic duct cell line into endocrine cells: involvement of PDX-1 and HNF3beta transcription factors. |
| 158 | 12124776 | Western blot analysis detected a progressive increase in protein levels of glucokinase and GLUT2 over 3 days of EX-4 treatment. |
| 159 | 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). |
| 160 | 12124776 | Double immunostaining showed that PDX-1 coexisted with insulin and glucagon in EX-4-treated cells. |
| 161 | 12124776 | EMSA results indicated that EX-4 caused a 12-fold increase in HNF3beta binding to PDX-1 promoter area II. |
| 162 | 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. |
| 163 | 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. |
| 164 | 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. |
| 165 | 12145169 | Foxa2 controls Pdx1 gene expression in pancreatic beta-cells in vivo. |
| 166 | 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. |
| 167 | 12145169 | To analyze the Foxa2/Pdx1 regulatory cascade during pancreatic beta-cell differentiation, we used conditional gene ablation of Foxa2 in mice. |
| 168 | 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. |
| 169 | 12145169 | These data represent the first in vivo demonstration that Foxa2 acts upstream of Pdx1 in the differentiated beta-cell. |
| 170 | 12145169 | Foxa2 controls Pdx1 gene expression in pancreatic beta-cells in vivo. |
| 171 | 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. |
| 172 | 12145169 | To analyze the Foxa2/Pdx1 regulatory cascade during pancreatic beta-cell differentiation, we used conditional gene ablation of Foxa2 in mice. |
| 173 | 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. |
| 174 | 12145169 | These data represent the first in vivo demonstration that Foxa2 acts upstream of Pdx1 in the differentiated beta-cell. |
| 175 | 12145169 | Foxa2 controls Pdx1 gene expression in pancreatic beta-cells in vivo. |
| 176 | 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. |
| 177 | 12145169 | To analyze the Foxa2/Pdx1 regulatory cascade during pancreatic beta-cell differentiation, we used conditional gene ablation of Foxa2 in mice. |
| 178 | 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. |
| 179 | 12145169 | These data represent the first in vivo demonstration that Foxa2 acts upstream of Pdx1 in the differentiated beta-cell. |
| 180 | 12145169 | Foxa2 controls Pdx1 gene expression in pancreatic beta-cells in vivo. |
| 181 | 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. |
| 182 | 12145169 | To analyze the Foxa2/Pdx1 regulatory cascade during pancreatic beta-cell differentiation, we used conditional gene ablation of Foxa2 in mice. |
| 183 | 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. |
| 184 | 12145169 | These data represent the first in vivo demonstration that Foxa2 acts upstream of Pdx1 in the differentiated beta-cell. |
| 185 | 12145169 | Foxa2 controls Pdx1 gene expression in pancreatic beta-cells in vivo. |
| 186 | 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. |
| 187 | 12145169 | To analyze the Foxa2/Pdx1 regulatory cascade during pancreatic beta-cell differentiation, we used conditional gene ablation of Foxa2 in mice. |
| 188 | 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. |
| 189 | 12145169 | These data represent the first in vivo demonstration that Foxa2 acts upstream of Pdx1 in the differentiated beta-cell. |
| 190 | 12646418 | HNF-1alpha and endodermal transcription factors cooperatively activate Fabpl: MODY3 mutations abrogate cooperativity. |
| 191 | 12646418 | An Fabpl transgene was directly activated through cognate sites by HNF-1alpha and HNF-1beta, as well as five other endodermal factors: CDX-1, C/EBPbeta, GATA-4, FoxA2, and HNF-4alpha. |
| 192 | 12646418 | HNF-1alpha activated the Fabpl transgene by as much as 60-fold greater in the presence of the other five endodermal factors than in their absence, accounting for up to one-half the total transgene activation by the group of six factors. |
| 193 | 12646418 | Furthermore, whereas wild-type HNF-1alpha exhibited pairwise cooperative synergy with each of the other five factors, the R131Q mutant could synergize only with GATA-4 and C/EBPbeta. |
| 194 | 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. |
| 195 | 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. |
| 196 | 15314688 | Foxa2 regulates multiple pathways of insulin secretion. |
| 197 | 15314688 | The regulation of insulin secretion by pancreatic beta cells is perturbed in several diseases, including adult-onset (type 2) diabetes and persistent hyperinsulinemic hypoglycemia of infancy (PHHI). |
| 198 | 15314688 | The first mouse model for PHHI has a conditional deletion of the gene encoding the winged-helix transcription factor Foxa2 (Forkhead box a2, formerly Hepatocyte nuclear factor 3beta) in pancreatic beta cells. |
| 199 | 15314688 | Using isolated islets, we found that Foxa2 deficiency resulted in excessive insulin release in response to amino acids and complete loss of glucose-stimulated insulin secretion. |
| 200 | 15314688 | Most PHHI cases are associated with mutations in SUR1 (Sulfonylurea receptor 1) or KIR6.2 (Inward rectifier K(+) channel member 6.2), which encode the subunits of the ATP-sensitive K(+) channel, and RNA in situ hybridization of mutant mouse islets revealed that expression of both genes is Foxa2 dependent. |
| 201 | 15314688 | Strikingly, one of these genes, Hadhsc, encodes short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase, deficiency of which has been shown to cause PHHI in humans. |
| 202 | 15314688 | Hadhsc is a direct target of Foxa2, as demonstrated by cotransfection as well as in vivo chromatin immunoprecipitation experiments using isolated islets. |
| 203 | 15314688 | Thus, we have established Foxa2 as an essential activator of genes that function in multiple pathways governing insulin secretion. |
| 204 | 15314688 | Foxa2 regulates multiple pathways of insulin secretion. |
| 205 | 15314688 | The regulation of insulin secretion by pancreatic beta cells is perturbed in several diseases, including adult-onset (type 2) diabetes and persistent hyperinsulinemic hypoglycemia of infancy (PHHI). |
| 206 | 15314688 | The first mouse model for PHHI has a conditional deletion of the gene encoding the winged-helix transcription factor Foxa2 (Forkhead box a2, formerly Hepatocyte nuclear factor 3beta) in pancreatic beta cells. |
| 207 | 15314688 | Using isolated islets, we found that Foxa2 deficiency resulted in excessive insulin release in response to amino acids and complete loss of glucose-stimulated insulin secretion. |
| 208 | 15314688 | Most PHHI cases are associated with mutations in SUR1 (Sulfonylurea receptor 1) or KIR6.2 (Inward rectifier K(+) channel member 6.2), which encode the subunits of the ATP-sensitive K(+) channel, and RNA in situ hybridization of mutant mouse islets revealed that expression of both genes is Foxa2 dependent. |
| 209 | 15314688 | Strikingly, one of these genes, Hadhsc, encodes short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase, deficiency of which has been shown to cause PHHI in humans. |
| 210 | 15314688 | Hadhsc is a direct target of Foxa2, as demonstrated by cotransfection as well as in vivo chromatin immunoprecipitation experiments using isolated islets. |
| 211 | 15314688 | Thus, we have established Foxa2 as an essential activator of genes that function in multiple pathways governing insulin secretion. |
| 212 | 15314688 | Foxa2 regulates multiple pathways of insulin secretion. |
| 213 | 15314688 | The regulation of insulin secretion by pancreatic beta cells is perturbed in several diseases, including adult-onset (type 2) diabetes and persistent hyperinsulinemic hypoglycemia of infancy (PHHI). |
| 214 | 15314688 | The first mouse model for PHHI has a conditional deletion of the gene encoding the winged-helix transcription factor Foxa2 (Forkhead box a2, formerly Hepatocyte nuclear factor 3beta) in pancreatic beta cells. |
| 215 | 15314688 | Using isolated islets, we found that Foxa2 deficiency resulted in excessive insulin release in response to amino acids and complete loss of glucose-stimulated insulin secretion. |
| 216 | 15314688 | Most PHHI cases are associated with mutations in SUR1 (Sulfonylurea receptor 1) or KIR6.2 (Inward rectifier K(+) channel member 6.2), which encode the subunits of the ATP-sensitive K(+) channel, and RNA in situ hybridization of mutant mouse islets revealed that expression of both genes is Foxa2 dependent. |
| 217 | 15314688 | Strikingly, one of these genes, Hadhsc, encodes short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase, deficiency of which has been shown to cause PHHI in humans. |
| 218 | 15314688 | Hadhsc is a direct target of Foxa2, as demonstrated by cotransfection as well as in vivo chromatin immunoprecipitation experiments using isolated islets. |
| 219 | 15314688 | Thus, we have established Foxa2 as an essential activator of genes that function in multiple pathways governing insulin secretion. |
| 220 | 15314688 | Foxa2 regulates multiple pathways of insulin secretion. |
| 221 | 15314688 | The regulation of insulin secretion by pancreatic beta cells is perturbed in several diseases, including adult-onset (type 2) diabetes and persistent hyperinsulinemic hypoglycemia of infancy (PHHI). |
| 222 | 15314688 | The first mouse model for PHHI has a conditional deletion of the gene encoding the winged-helix transcription factor Foxa2 (Forkhead box a2, formerly Hepatocyte nuclear factor 3beta) in pancreatic beta cells. |
| 223 | 15314688 | Using isolated islets, we found that Foxa2 deficiency resulted in excessive insulin release in response to amino acids and complete loss of glucose-stimulated insulin secretion. |
| 224 | 15314688 | Most PHHI cases are associated with mutations in SUR1 (Sulfonylurea receptor 1) or KIR6.2 (Inward rectifier K(+) channel member 6.2), which encode the subunits of the ATP-sensitive K(+) channel, and RNA in situ hybridization of mutant mouse islets revealed that expression of both genes is Foxa2 dependent. |
| 225 | 15314688 | Strikingly, one of these genes, Hadhsc, encodes short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase, deficiency of which has been shown to cause PHHI in humans. |
| 226 | 15314688 | Hadhsc is a direct target of Foxa2, as demonstrated by cotransfection as well as in vivo chromatin immunoprecipitation experiments using isolated islets. |
| 227 | 15314688 | Thus, we have established Foxa2 as an essential activator of genes that function in multiple pathways governing insulin secretion. |
| 228 | 15314688 | Foxa2 regulates multiple pathways of insulin secretion. |
| 229 | 15314688 | The regulation of insulin secretion by pancreatic beta cells is perturbed in several diseases, including adult-onset (type 2) diabetes and persistent hyperinsulinemic hypoglycemia of infancy (PHHI). |
| 230 | 15314688 | The first mouse model for PHHI has a conditional deletion of the gene encoding the winged-helix transcription factor Foxa2 (Forkhead box a2, formerly Hepatocyte nuclear factor 3beta) in pancreatic beta cells. |
| 231 | 15314688 | Using isolated islets, we found that Foxa2 deficiency resulted in excessive insulin release in response to amino acids and complete loss of glucose-stimulated insulin secretion. |
| 232 | 15314688 | Most PHHI cases are associated with mutations in SUR1 (Sulfonylurea receptor 1) or KIR6.2 (Inward rectifier K(+) channel member 6.2), which encode the subunits of the ATP-sensitive K(+) channel, and RNA in situ hybridization of mutant mouse islets revealed that expression of both genes is Foxa2 dependent. |
| 233 | 15314688 | Strikingly, one of these genes, Hadhsc, encodes short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase, deficiency of which has been shown to cause PHHI in humans. |
| 234 | 15314688 | Hadhsc is a direct target of Foxa2, as demonstrated by cotransfection as well as in vivo chromatin immunoprecipitation experiments using isolated islets. |
| 235 | 15314688 | Thus, we have established Foxa2 as an essential activator of genes that function in multiple pathways governing insulin secretion. |
| 236 | 15314688 | Foxa2 regulates multiple pathways of insulin secretion. |
| 237 | 15314688 | The regulation of insulin secretion by pancreatic beta cells is perturbed in several diseases, including adult-onset (type 2) diabetes and persistent hyperinsulinemic hypoglycemia of infancy (PHHI). |
| 238 | 15314688 | The first mouse model for PHHI has a conditional deletion of the gene encoding the winged-helix transcription factor Foxa2 (Forkhead box a2, formerly Hepatocyte nuclear factor 3beta) in pancreatic beta cells. |
| 239 | 15314688 | Using isolated islets, we found that Foxa2 deficiency resulted in excessive insulin release in response to amino acids and complete loss of glucose-stimulated insulin secretion. |
| 240 | 15314688 | Most PHHI cases are associated with mutations in SUR1 (Sulfonylurea receptor 1) or KIR6.2 (Inward rectifier K(+) channel member 6.2), which encode the subunits of the ATP-sensitive K(+) channel, and RNA in situ hybridization of mutant mouse islets revealed that expression of both genes is Foxa2 dependent. |
| 241 | 15314688 | Strikingly, one of these genes, Hadhsc, encodes short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase, deficiency of which has been shown to cause PHHI in humans. |
| 242 | 15314688 | Hadhsc is a direct target of Foxa2, as demonstrated by cotransfection as well as in vivo chromatin immunoprecipitation experiments using isolated islets. |
| 243 | 15314688 | Thus, we have established Foxa2 as an essential activator of genes that function in multiple pathways governing insulin secretion. |
| 244 | 15492844 | Human Forkhead-box (FOX) gene family consists of at least 43 members, including FOXA1, FOXA2, FOXA3, FOXB1, FOXC1, FOXC2, FOXD1, FOXD2, FOXD3, FOXD4, FOXD5 (FOXD4L1), FOXD6 (FOXD4L3), FOXE1, FOXE2, FOXE3, FOXF1, FOXF2, FOXG1 (FOXG1B), FOXH1, FOXI1, FOXJ1, FOXJ2, FOXJ3, FOXK1, FOXK2, FOXL1, FOXL2, FOXM1, FOXN1, FOXN2 (HTLF), FOXN3 (CHES1), FOXN4, FOXN5 (FOXR1), FOXN6 (FOXR2), FOXO1 (FOXO1A), FOXO2 (FOXO6), FOXO3 (FOXO3A), FOXO4 (MLLT7), FOXP1, FOXP2, FOXP3, FOXP4, and FOXQ1. |
| 245 | 15492844 | FOXH1 and FOXO1 mRNAs are expressed in human embryonic stem (ES) cells. |
| 246 | 15492844 | FOXC1, FOXC2, FOXE1, FOXE3, FOXL2, FOXN1, FOXP2 and FOXP3 genes are mutated in human congenital disorders. |
| 247 | 15492844 | FOXM1 gene is up-regulated in pancreatic cancer and basal cell carcinoma due to the transcriptional regulation by Sonic Hedgehog (SHH) pathway. |
| 248 | 15492844 | FOXO1 gene is fused to PAX3 or PAX7 genes in rhabdomyosarcoma. |
| 249 | 15492844 | FOXO3 and FOXO4 genes are fused to MLL gene in hematological malignancies. |
| 250 | 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. |
| 251 | 15616563 | Here we show that in normal mice, plasma insulin inhibits the forkhead transcription factor Foxa2 by nuclear exclusion and that in the fasted (low insulin) state Foxa2 activates transcriptional programmes of lipid metabolism and ketogenesis. |
| 252 | 15616563 | In insulin-resistant or hyperinsulinaemic mice, Foxa2 is inactive and permanently located in the cytoplasm of hepatocytes. |
| 253 | 15616563 | In these mice, adenoviral expression of Foxa2T156A, a nuclear, constitutively active Foxa2 that cannot be inhibited by insulin, decreases hepatic triglyceride content, increases hepatic insulin sensitivity, reduces glucose production, normalizes plasma glucose and significantly lowers plasma insulin. |
| 254 | 15616563 | Chronic hyperinsulinaemia in insulin-resistant syndromes results in the cytoplasmic localization and inactivation of Foxa2, thereby promoting lipid accumulation and insulin resistance in the liver. |
| 255 | 15616563 | Here we show that in normal mice, plasma insulin inhibits the forkhead transcription factor Foxa2 by nuclear exclusion and that in the fasted (low insulin) state Foxa2 activates transcriptional programmes of lipid metabolism and ketogenesis. |
| 256 | 15616563 | In insulin-resistant or hyperinsulinaemic mice, Foxa2 is inactive and permanently located in the cytoplasm of hepatocytes. |
| 257 | 15616563 | In these mice, adenoviral expression of Foxa2T156A, a nuclear, constitutively active Foxa2 that cannot be inhibited by insulin, decreases hepatic triglyceride content, increases hepatic insulin sensitivity, reduces glucose production, normalizes plasma glucose and significantly lowers plasma insulin. |
| 258 | 15616563 | Chronic hyperinsulinaemia in insulin-resistant syndromes results in the cytoplasmic localization and inactivation of Foxa2, thereby promoting lipid accumulation and insulin resistance in the liver. |
| 259 | 15616563 | Here we show that in normal mice, plasma insulin inhibits the forkhead transcription factor Foxa2 by nuclear exclusion and that in the fasted (low insulin) state Foxa2 activates transcriptional programmes of lipid metabolism and ketogenesis. |
| 260 | 15616563 | In insulin-resistant or hyperinsulinaemic mice, Foxa2 is inactive and permanently located in the cytoplasm of hepatocytes. |
| 261 | 15616563 | In these mice, adenoviral expression of Foxa2T156A, a nuclear, constitutively active Foxa2 that cannot be inhibited by insulin, decreases hepatic triglyceride content, increases hepatic insulin sensitivity, reduces glucose production, normalizes plasma glucose and significantly lowers plasma insulin. |
| 262 | 15616563 | Chronic hyperinsulinaemia in insulin-resistant syndromes results in the cytoplasmic localization and inactivation of Foxa2, thereby promoting lipid accumulation and insulin resistance in the liver. |
| 263 | 15616563 | Here we show that in normal mice, plasma insulin inhibits the forkhead transcription factor Foxa2 by nuclear exclusion and that in the fasted (low insulin) state Foxa2 activates transcriptional programmes of lipid metabolism and ketogenesis. |
| 264 | 15616563 | In insulin-resistant or hyperinsulinaemic mice, Foxa2 is inactive and permanently located in the cytoplasm of hepatocytes. |
| 265 | 15616563 | In these mice, adenoviral expression of Foxa2T156A, a nuclear, constitutively active Foxa2 that cannot be inhibited by insulin, decreases hepatic triglyceride content, increases hepatic insulin sensitivity, reduces glucose production, normalizes plasma glucose and significantly lowers plasma insulin. |
| 266 | 15616563 | Chronic hyperinsulinaemia in insulin-resistant syndromes results in the cytoplasmic localization and inactivation of Foxa2, thereby promoting lipid accumulation and insulin resistance in the liver. |
| 267 | 15630453 | The abundance of mRNAs for Glut2 and HNF3beta was reduced in islets of betaPKClambda(-/-) mice, and the expression of genes regulated by HNF3beta was also affected (that of Sur1 and Kir6.2 genes was reduced, whereas that of hexokinase 1 and hexokinase 2 genes was increased). |
| 268 | 15630453 | Normalization of HNF3beta expression by infection of islets from betaPKClambda(-/-) mice with an adenoviral vector significantly reversed the defect in glucose-stimulated insulin secretion. |
| 269 | 15630453 | The abundance of mRNAs for Glut2 and HNF3beta was reduced in islets of betaPKClambda(-/-) mice, and the expression of genes regulated by HNF3beta was also affected (that of Sur1 and Kir6.2 genes was reduced, whereas that of hexokinase 1 and hexokinase 2 genes was increased). |
| 270 | 15630453 | Normalization of HNF3beta expression by infection of islets from betaPKClambda(-/-) mice with an adenoviral vector significantly reversed the defect in glucose-stimulated insulin secretion. |
| 271 | 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. |
| 272 | 15631623 | Deletion of the Foxa2 gene in pancreatic beta-cells in mice results in a phenotype resembling PHHI (persistent hyperinsulinaemic hypoglycaemia of infancy). |
| 273 | 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. |
| 274 | 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. |
| 275 | 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. |
| 276 | 15631623 | Deletion of the Foxa2 gene in pancreatic beta-cells in mice results in a phenotype resembling PHHI (persistent hyperinsulinaemic hypoglycaemia of infancy). |
| 277 | 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. |
| 278 | 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. |
| 279 | 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. |
| 280 | 15631623 | Deletion of the Foxa2 gene in pancreatic beta-cells in mice results in a phenotype resembling PHHI (persistent hyperinsulinaemic hypoglycaemia of infancy). |
| 281 | 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. |
| 282 | 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. |
| 283 | 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. |
| 284 | 15631623 | Deletion of the Foxa2 gene in pancreatic beta-cells in mice results in a phenotype resembling PHHI (persistent hyperinsulinaemic hypoglycaemia of infancy). |
| 285 | 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. |
| 286 | 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. |
| 287 | 15680365 | By marker gene analysis, we show that the expression of the alpha-cell transcription factors Arx, Pax6, and Brn4 does not require Foxa2 in the transcriptional hierarchy governing alpha-cell differentiation. |
| 288 | 15949766 | Foxa2 (Hnf3beta) is a winged-helix/forkhead transcription factor that regulates gene expression in the liver, pancreatic islets and adipocytes. |
| 289 | 15949766 | Hyperinsulinemia-mediated inactivation of Foxa2 by nuclear exclusion has recently been implicated in the development of liver steatosis and insulin resistance in three animal models of diabetes. |
| 290 | 15949766 | Foxa2 (Hnf3beta) is a winged-helix/forkhead transcription factor that regulates gene expression in the liver, pancreatic islets and adipocytes. |
| 291 | 15949766 | Hyperinsulinemia-mediated inactivation of Foxa2 by nuclear exclusion has recently been implicated in the development of liver steatosis and insulin resistance in three animal models of diabetes. |
| 292 | 16079311 | The effect on EB development of supplementation with basic fibroblast growth factor (FGF2) was also studied. |
| 293 | 16079311 | We conclude that physiological glucose concentrations are suitable for the culturing of EBs, that the addition of FGF2 enhances the temporal expression of genes including POU5F1, nestin, FOXA2, ONECUT1, NEUROD1, PAX6, and insulin, and that EBs can be cultured in vitro for long periods, allowing for further examination of developmental processes. |
| 294 | 16179348 | Agonists for the nuclear receptor peroxisomal proliferator-activated receptor-gamma (PPARgamma) and its heterodimeric partner, retinoid X receptor (RXR), are effective agents for the treatment of type 2 diabetes. |
| 295 | 16179348 | Troglitazone increased skeletal muscle Irs-1 and phospho-Akt levels following in vivo insulin treatment, whereas AGN194204 increased hepatic Irs-2 and insulin stimulated phospho-Akt in liver. |
| 296 | 16179348 | Gene profiles of AGN194204-treated mouse liver analyzed by Ingenuity Pathway Analysis identified increases in fatty acid synthetic genes, including Srebp-1 and fatty acid synthase, a pathway previously shown to be induced by RXR agonists. |
| 297 | 16179348 | A network of down-regulated genes containing Foxa2, Foxa3, and G-protein subunits was identified, and decreases in these mRNA levels were confirmed by quantitative reverse transcription-PCR. |
| 298 | 16179348 | These studies demonstrate distinct molecular events lead to insulin sensitization by high affinity RXR and PPARgamma agonists. |
| 299 | 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. |
| 300 | 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. |
| 301 | 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. |
| 302 | 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. |
| 303 | 16459311 | Coactivation of Foxa2 through Pgc-1beta promotes liver fatty acid oxidation and triglyceride/VLDL secretion. |
| 304 | 16459311 | Adenoviral expression of Foxa2 and Pgc-1beta in livers of ob/ob mice results in decreased hepatic TAG content and increased plasma TAG concentrations. |
| 305 | 16459311 | In addition, the concerted action of Foxa2/Pgc-1beta activates genes in mitochondrial beta oxidation and enhances fatty acid metabolism. |
| 306 | 16459311 | Furthermore, Foxa2/Pgc-1beta induce the expression of microsomal transfer protein, thereby increasing apoB-containing VLDL secretion. |
| 307 | 16459311 | These data demonstrate that Foxa2/Pgc-1beta regulate hepatic lipid homeostasis by affecting the clearance rate of fatty acids through oxidation and/or secretion of lipids in response to insulin. |
| 308 | 16459311 | Coactivation of Foxa2 through Pgc-1beta promotes liver fatty acid oxidation and triglyceride/VLDL secretion. |
| 309 | 16459311 | Adenoviral expression of Foxa2 and Pgc-1beta in livers of ob/ob mice results in decreased hepatic TAG content and increased plasma TAG concentrations. |
| 310 | 16459311 | In addition, the concerted action of Foxa2/Pgc-1beta activates genes in mitochondrial beta oxidation and enhances fatty acid metabolism. |
| 311 | 16459311 | Furthermore, Foxa2/Pgc-1beta induce the expression of microsomal transfer protein, thereby increasing apoB-containing VLDL secretion. |
| 312 | 16459311 | These data demonstrate that Foxa2/Pgc-1beta regulate hepatic lipid homeostasis by affecting the clearance rate of fatty acids through oxidation and/or secretion of lipids in response to insulin. |
| 313 | 16459311 | Coactivation of Foxa2 through Pgc-1beta promotes liver fatty acid oxidation and triglyceride/VLDL secretion. |
| 314 | 16459311 | Adenoviral expression of Foxa2 and Pgc-1beta in livers of ob/ob mice results in decreased hepatic TAG content and increased plasma TAG concentrations. |
| 315 | 16459311 | In addition, the concerted action of Foxa2/Pgc-1beta activates genes in mitochondrial beta oxidation and enhances fatty acid metabolism. |
| 316 | 16459311 | Furthermore, Foxa2/Pgc-1beta induce the expression of microsomal transfer protein, thereby increasing apoB-containing VLDL secretion. |
| 317 | 16459311 | These data demonstrate that Foxa2/Pgc-1beta regulate hepatic lipid homeostasis by affecting the clearance rate of fatty acids through oxidation and/or secretion of lipids in response to insulin. |
| 318 | 16459311 | Coactivation of Foxa2 through Pgc-1beta promotes liver fatty acid oxidation and triglyceride/VLDL secretion. |
| 319 | 16459311 | Adenoviral expression of Foxa2 and Pgc-1beta in livers of ob/ob mice results in decreased hepatic TAG content and increased plasma TAG concentrations. |
| 320 | 16459311 | In addition, the concerted action of Foxa2/Pgc-1beta activates genes in mitochondrial beta oxidation and enhances fatty acid metabolism. |
| 321 | 16459311 | Furthermore, Foxa2/Pgc-1beta induce the expression of microsomal transfer protein, thereby increasing apoB-containing VLDL secretion. |
| 322 | 16459311 | These data demonstrate that Foxa2/Pgc-1beta regulate hepatic lipid homeostasis by affecting the clearance rate of fatty acids through oxidation and/or secretion of lipids in response to insulin. |
| 323 | 16459311 | Coactivation of Foxa2 through Pgc-1beta promotes liver fatty acid oxidation and triglyceride/VLDL secretion. |
| 324 | 16459311 | Adenoviral expression of Foxa2 and Pgc-1beta in livers of ob/ob mice results in decreased hepatic TAG content and increased plasma TAG concentrations. |
| 325 | 16459311 | In addition, the concerted action of Foxa2/Pgc-1beta activates genes in mitochondrial beta oxidation and enhances fatty acid metabolism. |
| 326 | 16459311 | Furthermore, Foxa2/Pgc-1beta induce the expression of microsomal transfer protein, thereby increasing apoB-containing VLDL secretion. |
| 327 | 16459311 | These data demonstrate that Foxa2/Pgc-1beta regulate hepatic lipid homeostasis by affecting the clearance rate of fatty acids through oxidation and/or secretion of lipids in response to insulin. |
| 328 | 16483925 | A study by Wolfrum and Stoffel (2006) shows that the forkhead protein Foxa2 stimulates hepatic VLDL production in concert with the coactivator PGC-1beta and that insulin inhibits this process by inactivating Foxa2. |
| 329 | 16644672 | The glucoincretin hormone glucagon-like peptide-1 (GLP-1) increases pancreatic beta-cell proliferation and survival through sequential activation of the epidermal growth factor receptor (EGFR), phosphatidylinositol-3 kinase (PI 3-kinase), and Akt. |
| 330 | 16644672 | GLP-1 inhibited FoxO1 through phosphorylation-dependent nuclear exclusion in pancreatic beta (INS832/13) cells. |
| 331 | 16644672 | The effect of GLP-1 was suppressed by inhibitors of EGFR (AG1478) and PI 3-kinase (LY294002). |
| 332 | 16644672 | Gene expression and chromatin immunoprecipitation assays demonstrated that GLP-1 increases pancreatic and duodenal homeobox gene-1 and Foxa2 expression and inhibits FoxO1 binding to both promoters. |
| 333 | 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. |
| 334 | 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. |
| 335 | 17327429 | PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic beta-cells. |
| 336 | 17327429 | Transgenic mice with beta-cell-specific overexpression of ped/pea-15 (beta-tg) exhibited decreased glucose tolerance but were not insulin resistant. |
| 337 | 17327429 | Islets from the beta-tg also exhibited little response to glucose. mRNAs encoding the Sur1 and Kir6.2 potassium channel subunits and their upstream regulator Foxa2 were specifically reduced in these islets. |
| 338 | 17327429 | Overexpression of PED/PEA-15 inhibited the induction of the atypical protein kinase C (PKC)-zeta by glucose in mouse islets and in beta-cells of the MIN-6 and INS-1 lines. |
| 339 | 17327429 | Rescue of PKC-zeta activity elicited recovery of the expression of the Sur1, Kir6.2, and Foxa2 genes and of glucose-induced insulin secretion in PED/PEA-15-overexpressing beta-cells. |
| 340 | 17327429 | Islets from ped/pea-15-null mice exhibited a twofold increased activation of PKC-zeta by glucose; increased abundance of the Sur1, Kir6.2, and Foxa2 mRNAs; and enhanced glucose effect on insulin secretion. |
| 341 | 17327429 | In conclusion, PED/PEA-15 is an endogenous regulator of glucose-induced insulin secretion, which restrains potassium channel expression in pancreatic beta-cells. |
| 342 | 17327429 | PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic beta-cells. |
| 343 | 17327429 | Transgenic mice with beta-cell-specific overexpression of ped/pea-15 (beta-tg) exhibited decreased glucose tolerance but were not insulin resistant. |
| 344 | 17327429 | Islets from the beta-tg also exhibited little response to glucose. mRNAs encoding the Sur1 and Kir6.2 potassium channel subunits and their upstream regulator Foxa2 were specifically reduced in these islets. |
| 345 | 17327429 | Overexpression of PED/PEA-15 inhibited the induction of the atypical protein kinase C (PKC)-zeta by glucose in mouse islets and in beta-cells of the MIN-6 and INS-1 lines. |
| 346 | 17327429 | Rescue of PKC-zeta activity elicited recovery of the expression of the Sur1, Kir6.2, and Foxa2 genes and of glucose-induced insulin secretion in PED/PEA-15-overexpressing beta-cells. |
| 347 | 17327429 | Islets from ped/pea-15-null mice exhibited a twofold increased activation of PKC-zeta by glucose; increased abundance of the Sur1, Kir6.2, and Foxa2 mRNAs; and enhanced glucose effect on insulin secretion. |
| 348 | 17327429 | In conclusion, PED/PEA-15 is an endogenous regulator of glucose-induced insulin secretion, which restrains potassium channel expression in pancreatic beta-cells. |
| 349 | 17327429 | PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic beta-cells. |
| 350 | 17327429 | Transgenic mice with beta-cell-specific overexpression of ped/pea-15 (beta-tg) exhibited decreased glucose tolerance but were not insulin resistant. |
| 351 | 17327429 | Islets from the beta-tg also exhibited little response to glucose. mRNAs encoding the Sur1 and Kir6.2 potassium channel subunits and their upstream regulator Foxa2 were specifically reduced in these islets. |
| 352 | 17327429 | Overexpression of PED/PEA-15 inhibited the induction of the atypical protein kinase C (PKC)-zeta by glucose in mouse islets and in beta-cells of the MIN-6 and INS-1 lines. |
| 353 | 17327429 | Rescue of PKC-zeta activity elicited recovery of the expression of the Sur1, Kir6.2, and Foxa2 genes and of glucose-induced insulin secretion in PED/PEA-15-overexpressing beta-cells. |
| 354 | 17327429 | Islets from ped/pea-15-null mice exhibited a twofold increased activation of PKC-zeta by glucose; increased abundance of the Sur1, Kir6.2, and Foxa2 mRNAs; and enhanced glucose effect on insulin secretion. |
| 355 | 17327429 | In conclusion, PED/PEA-15 is an endogenous regulator of glucose-induced insulin secretion, which restrains potassium channel expression in pancreatic beta-cells. |
| 356 | 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). |
| 357 | 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. |
| 358 | 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. |
| 359 | 17510217 | The aggregates were finally matured in the presence of insulin-like growth factor II and nicotinamide. |
| 360 | 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. |
| 361 | 17510498 | FoxO1 is expressed in a subset of pancreatic duct cells, in which insulin and/or Pdx1 are occasionally expressed. |
| 362 | 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. |
| 363 | 17563382 | A small set of transcription factors, including Tcf2, Onecut1, and Foxa2, has been identified in these pancreatic progenitor cells. |
| 364 | 17563382 | In turn, both Foxa2 and Tcf2 regulated Sox9 expression, demonstrating feedback circuits between these genes. |
| 365 | 17563382 | Furthermore, Sox9 activated the expression of the proendocrine factor Neurogenin3, which also depends on the other members of the progenitor transcription network. |
| 366 | 17563382 | A small set of transcription factors, including Tcf2, Onecut1, and Foxa2, has been identified in these pancreatic progenitor cells. |
| 367 | 17563382 | In turn, both Foxa2 and Tcf2 regulated Sox9 expression, demonstrating feedback circuits between these genes. |
| 368 | 17563382 | Furthermore, Sox9 activated the expression of the proendocrine factor Neurogenin3, which also depends on the other members of the progenitor transcription network. |
| 369 | 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. |
| 370 | 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. |
| 371 | 18378016 | Islet Neogenesis Associated Protein (INGAP) increases pancreatic beta-cell mass and potentiates glucose-induced insulin secretion. |
| 372 | 18378016 | Thereafter, gene (RT-PCR) and protein expression (Western blotting) of Foxa2, SUR1 and Kir6.2, cytoplasmic Ca(2+) ([Ca(2+)](i)), static and dynamic insulin secretion, and (86)Rb efflux were measured. |
| 373 | 18378016 | INGAP-PP increased the expression levels of Kir6.2, SUR1 and Foxa2 genes, and SUR1 and Foxa2 proteins. |
| 374 | 18378016 | Islet Neogenesis Associated Protein (INGAP) increases pancreatic beta-cell mass and potentiates glucose-induced insulin secretion. |
| 375 | 18378016 | Thereafter, gene (RT-PCR) and protein expression (Western blotting) of Foxa2, SUR1 and Kir6.2, cytoplasmic Ca(2+) ([Ca(2+)](i)), static and dynamic insulin secretion, and (86)Rb efflux were measured. |
| 376 | 18378016 | INGAP-PP increased the expression levels of Kir6.2, SUR1 and Foxa2 genes, and SUR1 and Foxa2 proteins. |
| 377 | 18381283 | Foxa2 activity increases plasma high density lipoprotein levels by regulating apolipoprotein M. |
| 378 | 18381283 | Here we demonstrate that insulin, through a Foxa2-mediated mechanism, inhibited the expression of apolipoprotein M (apoM), an important determinant of plasma pre-beta-HDL and alpha-HDL concentrations. |
| 379 | 18381283 | Obese mice had decreased apoM expression and plasma pre-beta-HDL levels due to inactivation of Foxa2 in hyperinsulinemic states. |
| 380 | 18381283 | Nuclear reexpression of Foxa2 with a phosphorylation-deficient mutant Foxa2T156A (Ad-T156A) activated apoM expression and increased plasma pre-beta-HDL and alpha-HDL levels. |
| 381 | 18381283 | In contrast, haploinsufficient Foxa2(+/-) mice exhibited decreased hepatic apoM expression and plasma pre-beta-HDL and HDL levels. |
| 382 | 18381283 | The increase in plasma HDL levels and pre-beta-HDL formation by Foxa2 was mediated exclusively by apoM, as constitutive active expression of Foxa2 in apoM(-/-) mice had no effect on plasma HDL levels. |
| 383 | 18381283 | Foxa2 activity increases plasma high density lipoprotein levels by regulating apolipoprotein M. |
| 384 | 18381283 | Here we demonstrate that insulin, through a Foxa2-mediated mechanism, inhibited the expression of apolipoprotein M (apoM), an important determinant of plasma pre-beta-HDL and alpha-HDL concentrations. |
| 385 | 18381283 | Obese mice had decreased apoM expression and plasma pre-beta-HDL levels due to inactivation of Foxa2 in hyperinsulinemic states. |
| 386 | 18381283 | Nuclear reexpression of Foxa2 with a phosphorylation-deficient mutant Foxa2T156A (Ad-T156A) activated apoM expression and increased plasma pre-beta-HDL and alpha-HDL levels. |
| 387 | 18381283 | In contrast, haploinsufficient Foxa2(+/-) mice exhibited decreased hepatic apoM expression and plasma pre-beta-HDL and HDL levels. |
| 388 | 18381283 | The increase in plasma HDL levels and pre-beta-HDL formation by Foxa2 was mediated exclusively by apoM, as constitutive active expression of Foxa2 in apoM(-/-) mice had no effect on plasma HDL levels. |
| 389 | 18381283 | Foxa2 activity increases plasma high density lipoprotein levels by regulating apolipoprotein M. |
| 390 | 18381283 | Here we demonstrate that insulin, through a Foxa2-mediated mechanism, inhibited the expression of apolipoprotein M (apoM), an important determinant of plasma pre-beta-HDL and alpha-HDL concentrations. |
| 391 | 18381283 | Obese mice had decreased apoM expression and plasma pre-beta-HDL levels due to inactivation of Foxa2 in hyperinsulinemic states. |
| 392 | 18381283 | Nuclear reexpression of Foxa2 with a phosphorylation-deficient mutant Foxa2T156A (Ad-T156A) activated apoM expression and increased plasma pre-beta-HDL and alpha-HDL levels. |
| 393 | 18381283 | In contrast, haploinsufficient Foxa2(+/-) mice exhibited decreased hepatic apoM expression and plasma pre-beta-HDL and HDL levels. |
| 394 | 18381283 | The increase in plasma HDL levels and pre-beta-HDL formation by Foxa2 was mediated exclusively by apoM, as constitutive active expression of Foxa2 in apoM(-/-) mice had no effect on plasma HDL levels. |
| 395 | 18381283 | Foxa2 activity increases plasma high density lipoprotein levels by regulating apolipoprotein M. |
| 396 | 18381283 | Here we demonstrate that insulin, through a Foxa2-mediated mechanism, inhibited the expression of apolipoprotein M (apoM), an important determinant of plasma pre-beta-HDL and alpha-HDL concentrations. |
| 397 | 18381283 | Obese mice had decreased apoM expression and plasma pre-beta-HDL levels due to inactivation of Foxa2 in hyperinsulinemic states. |
| 398 | 18381283 | Nuclear reexpression of Foxa2 with a phosphorylation-deficient mutant Foxa2T156A (Ad-T156A) activated apoM expression and increased plasma pre-beta-HDL and alpha-HDL levels. |
| 399 | 18381283 | In contrast, haploinsufficient Foxa2(+/-) mice exhibited decreased hepatic apoM expression and plasma pre-beta-HDL and HDL levels. |
| 400 | 18381283 | The increase in plasma HDL levels and pre-beta-HDL formation by Foxa2 was mediated exclusively by apoM, as constitutive active expression of Foxa2 in apoM(-/-) mice had no effect on plasma HDL levels. |
| 401 | 18381283 | Foxa2 activity increases plasma high density lipoprotein levels by regulating apolipoprotein M. |
| 402 | 18381283 | Here we demonstrate that insulin, through a Foxa2-mediated mechanism, inhibited the expression of apolipoprotein M (apoM), an important determinant of plasma pre-beta-HDL and alpha-HDL concentrations. |
| 403 | 18381283 | Obese mice had decreased apoM expression and plasma pre-beta-HDL levels due to inactivation of Foxa2 in hyperinsulinemic states. |
| 404 | 18381283 | Nuclear reexpression of Foxa2 with a phosphorylation-deficient mutant Foxa2T156A (Ad-T156A) activated apoM expression and increased plasma pre-beta-HDL and alpha-HDL levels. |
| 405 | 18381283 | In contrast, haploinsufficient Foxa2(+/-) mice exhibited decreased hepatic apoM expression and plasma pre-beta-HDL and HDL levels. |
| 406 | 18381283 | The increase in plasma HDL levels and pre-beta-HDL formation by Foxa2 was mediated exclusively by apoM, as constitutive active expression of Foxa2 in apoM(-/-) mice had no effect on plasma HDL levels. |
| 407 | 18753309 | Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression. |
| 408 | 18753309 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP/G6PC2) is a major autoantigen in both mouse and human type 1 diabetes. |
| 409 | 18753309 | Chromatin immunoprecipitation (ChIP) assays have shown that the IGRP promoter binds the islet-enriched transcription factors Pax-6 and BETA2. |
| 410 | 18753309 | We show here, again using ChIP assays, that the IGRP promoter also binds the islet-enriched transcription factors MafA and Foxa2. |
| 411 | 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. |
| 412 | 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. |
| 413 | 18753309 | Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression. |
| 414 | 18753309 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP/G6PC2) is a major autoantigen in both mouse and human type 1 diabetes. |
| 415 | 18753309 | Chromatin immunoprecipitation (ChIP) assays have shown that the IGRP promoter binds the islet-enriched transcription factors Pax-6 and BETA2. |
| 416 | 18753309 | We show here, again using ChIP assays, that the IGRP promoter also binds the islet-enriched transcription factors MafA and Foxa2. |
| 417 | 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. |
| 418 | 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. |
| 419 | 18753309 | Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression. |
| 420 | 18753309 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP/G6PC2) is a major autoantigen in both mouse and human type 1 diabetes. |
| 421 | 18753309 | Chromatin immunoprecipitation (ChIP) assays have shown that the IGRP promoter binds the islet-enriched transcription factors Pax-6 and BETA2. |
| 422 | 18753309 | We show here, again using ChIP assays, that the IGRP promoter also binds the islet-enriched transcription factors MafA and Foxa2. |
| 423 | 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. |
| 424 | 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. |
| 425 | 19433262 | SLC2A2 gene expression in kidney of diabetic rats is regulated by HNF-1alpha and HNF-3beta. |
| 426 | 19433262 | We hypothesize that, in kidney of diabetic rats, hepatocyte nuclear factors (HNF-1alpha and HNF-3beta) play a critical role in the overexpression of solute carrier 2A2 (SLC2A2) gene. |
| 427 | 19433262 | Twofold increase in GLUT2 mRNA was observed in diabetic, accompanied by significant increases in HNF-1alpha and HNF-3beta expression and binding activity. |
| 428 | 19433262 | Additional 2-fold increase in GLUT2 mRNA and HNF-3beta expression/activity was observed in 12-h insulin-treated rats. |
| 429 | 19433262 | Six-day insulin treatment decreased GLUT2 mRNA and HNF-1alpha expression and activity to levels of non-diabetic rats, whereas HNF-3beta decreased to levels of non-insulin-treated diabetic rats. |
| 430 | 19433262 | Our results provide evidence for a link between the overexpression of SLC2A2 gene and the transcriptional activity of HNF-1alpha and HNF-3beta in kidney of diabetic rats. |
| 431 | 19433262 | Furthermore, recovery of SLC2A2 gene after 6-day insulin treatment also involves HNF-1alpha and HNF-3beta activity. |
| 432 | 19433262 | SLC2A2 gene expression in kidney of diabetic rats is regulated by HNF-1alpha and HNF-3beta. |
| 433 | 19433262 | We hypothesize that, in kidney of diabetic rats, hepatocyte nuclear factors (HNF-1alpha and HNF-3beta) play a critical role in the overexpression of solute carrier 2A2 (SLC2A2) gene. |
| 434 | 19433262 | Twofold increase in GLUT2 mRNA was observed in diabetic, accompanied by significant increases in HNF-1alpha and HNF-3beta expression and binding activity. |
| 435 | 19433262 | Additional 2-fold increase in GLUT2 mRNA and HNF-3beta expression/activity was observed in 12-h insulin-treated rats. |
| 436 | 19433262 | Six-day insulin treatment decreased GLUT2 mRNA and HNF-1alpha expression and activity to levels of non-diabetic rats, whereas HNF-3beta decreased to levels of non-insulin-treated diabetic rats. |
| 437 | 19433262 | Our results provide evidence for a link between the overexpression of SLC2A2 gene and the transcriptional activity of HNF-1alpha and HNF-3beta in kidney of diabetic rats. |
| 438 | 19433262 | Furthermore, recovery of SLC2A2 gene after 6-day insulin treatment also involves HNF-1alpha and HNF-3beta activity. |
| 439 | 19433262 | SLC2A2 gene expression in kidney of diabetic rats is regulated by HNF-1alpha and HNF-3beta. |
| 440 | 19433262 | We hypothesize that, in kidney of diabetic rats, hepatocyte nuclear factors (HNF-1alpha and HNF-3beta) play a critical role in the overexpression of solute carrier 2A2 (SLC2A2) gene. |
| 441 | 19433262 | Twofold increase in GLUT2 mRNA was observed in diabetic, accompanied by significant increases in HNF-1alpha and HNF-3beta expression and binding activity. |
| 442 | 19433262 | Additional 2-fold increase in GLUT2 mRNA and HNF-3beta expression/activity was observed in 12-h insulin-treated rats. |
| 443 | 19433262 | Six-day insulin treatment decreased GLUT2 mRNA and HNF-1alpha expression and activity to levels of non-diabetic rats, whereas HNF-3beta decreased to levels of non-insulin-treated diabetic rats. |
| 444 | 19433262 | Our results provide evidence for a link between the overexpression of SLC2A2 gene and the transcriptional activity of HNF-1alpha and HNF-3beta in kidney of diabetic rats. |
| 445 | 19433262 | Furthermore, recovery of SLC2A2 gene after 6-day insulin treatment also involves HNF-1alpha and HNF-3beta activity. |
| 446 | 19433262 | SLC2A2 gene expression in kidney of diabetic rats is regulated by HNF-1alpha and HNF-3beta. |
| 447 | 19433262 | We hypothesize that, in kidney of diabetic rats, hepatocyte nuclear factors (HNF-1alpha and HNF-3beta) play a critical role in the overexpression of solute carrier 2A2 (SLC2A2) gene. |
| 448 | 19433262 | Twofold increase in GLUT2 mRNA was observed in diabetic, accompanied by significant increases in HNF-1alpha and HNF-3beta expression and binding activity. |
| 449 | 19433262 | Additional 2-fold increase in GLUT2 mRNA and HNF-3beta expression/activity was observed in 12-h insulin-treated rats. |
| 450 | 19433262 | Six-day insulin treatment decreased GLUT2 mRNA and HNF-1alpha expression and activity to levels of non-diabetic rats, whereas HNF-3beta decreased to levels of non-insulin-treated diabetic rats. |
| 451 | 19433262 | Our results provide evidence for a link between the overexpression of SLC2A2 gene and the transcriptional activity of HNF-1alpha and HNF-3beta in kidney of diabetic rats. |
| 452 | 19433262 | Furthermore, recovery of SLC2A2 gene after 6-day insulin treatment also involves HNF-1alpha and HNF-3beta activity. |
| 453 | 19433262 | SLC2A2 gene expression in kidney of diabetic rats is regulated by HNF-1alpha and HNF-3beta. |
| 454 | 19433262 | We hypothesize that, in kidney of diabetic rats, hepatocyte nuclear factors (HNF-1alpha and HNF-3beta) play a critical role in the overexpression of solute carrier 2A2 (SLC2A2) gene. |
| 455 | 19433262 | Twofold increase in GLUT2 mRNA was observed in diabetic, accompanied by significant increases in HNF-1alpha and HNF-3beta expression and binding activity. |
| 456 | 19433262 | Additional 2-fold increase in GLUT2 mRNA and HNF-3beta expression/activity was observed in 12-h insulin-treated rats. |
| 457 | 19433262 | Six-day insulin treatment decreased GLUT2 mRNA and HNF-1alpha expression and activity to levels of non-diabetic rats, whereas HNF-3beta decreased to levels of non-insulin-treated diabetic rats. |
| 458 | 19433262 | Our results provide evidence for a link between the overexpression of SLC2A2 gene and the transcriptional activity of HNF-1alpha and HNF-3beta in kidney of diabetic rats. |
| 459 | 19433262 | Furthermore, recovery of SLC2A2 gene after 6-day insulin treatment also involves HNF-1alpha and HNF-3beta activity. |
| 460 | 19436110 | Foxa1 and Foxa2 regulate bile duct development in mice. |
| 461 | 19436110 | The forkhead box proteins A1 and A2 (Foxa1 and Foxa2) are transcription factors with critical roles in establishing the developmental competence of the foregut endoderm and in initiating liver specification. |
| 462 | 19436110 | Using conditional gene ablation during a later phase of liver development, we show here that deletion of both Foxa1 and Foxa2 (Foxa1/2) in the embryonic liver caused hyperplasia of the biliary tree. |
| 463 | 19436110 | Abnormal bile duct formation in Foxa1/2-deficient liver was due, at least in part, to activation of IL-6 expression, a proliferative signal for cholangiocytes. |
| 464 | 19436110 | The glucocorticoid receptor is a negative regulator of IL-6 transcription; in the absence of Foxa1/2, the glucocorticoid receptor failed to bind to the IL-6 promoter, causing enhanced IL-6 expression. |
| 465 | 19436110 | Our data suggest that Foxa1/2 function as terminators of bile duct expansion in the adult liver through inhibition of IL-6 expression. |
| 466 | 19436110 | Foxa1 and Foxa2 regulate bile duct development in mice. |
| 467 | 19436110 | The forkhead box proteins A1 and A2 (Foxa1 and Foxa2) are transcription factors with critical roles in establishing the developmental competence of the foregut endoderm and in initiating liver specification. |
| 468 | 19436110 | Using conditional gene ablation during a later phase of liver development, we show here that deletion of both Foxa1 and Foxa2 (Foxa1/2) in the embryonic liver caused hyperplasia of the biliary tree. |
| 469 | 19436110 | Abnormal bile duct formation in Foxa1/2-deficient liver was due, at least in part, to activation of IL-6 expression, a proliferative signal for cholangiocytes. |
| 470 | 19436110 | The glucocorticoid receptor is a negative regulator of IL-6 transcription; in the absence of Foxa1/2, the glucocorticoid receptor failed to bind to the IL-6 promoter, causing enhanced IL-6 expression. |
| 471 | 19436110 | Our data suggest that Foxa1/2 function as terminators of bile duct expansion in the adult liver through inhibition of IL-6 expression. |
| 472 | 19436110 | Foxa1 and Foxa2 regulate bile duct development in mice. |
| 473 | 19436110 | The forkhead box proteins A1 and A2 (Foxa1 and Foxa2) are transcription factors with critical roles in establishing the developmental competence of the foregut endoderm and in initiating liver specification. |
| 474 | 19436110 | Using conditional gene ablation during a later phase of liver development, we show here that deletion of both Foxa1 and Foxa2 (Foxa1/2) in the embryonic liver caused hyperplasia of the biliary tree. |
| 475 | 19436110 | Abnormal bile duct formation in Foxa1/2-deficient liver was due, at least in part, to activation of IL-6 expression, a proliferative signal for cholangiocytes. |
| 476 | 19436110 | The glucocorticoid receptor is a negative regulator of IL-6 transcription; in the absence of Foxa1/2, the glucocorticoid receptor failed to bind to the IL-6 promoter, causing enhanced IL-6 expression. |
| 477 | 19436110 | Our data suggest that Foxa1/2 function as terminators of bile duct expansion in the adult liver through inhibition of IL-6 expression. |
| 478 | 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. |
| 479 | 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. |
| 480 | 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. |
| 481 | 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. |
| 482 | 19487809 | Pdx1 also occupied regulatory sequences in Foxa2 and Hnf1b. |
| 483 | 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. |
| 484 | 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. |
| 485 | 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. |
| 486 | 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. |
| 487 | 19487809 | Pdx1 also occupied regulatory sequences in Foxa2 and Hnf1b. |
| 488 | 19544426 | Subsequent single-cell cloning resulted in a homogeneous cell population with a CD29(+)CD44(+)Sca-1(+) surface antigen expression profile. |
| 489 | 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). |
| 490 | 20158571 | MafA promotes the reprogramming of placenta-derived multipotent stem cells into pancreatic islets-like and insulin+ cells. |
| 491 | 20158571 | MafA is a pancreatic transcriptional factor that controls β-cell-specific transcription of the insulin gene. |
| 492 | 20158571 | In this study, we investigate the role of MafA in placenta-derived multipotent stem cells (PDMSCs) that constitutively expressed Oct-4 and Nanog. |
| 493 | 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). |
| 494 | 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. |
| 495 | 20158571 | The glucose-stimulated responses to insulin and c-peptide production in MafA-overexpressing PDMSCs were significantly higher than in PDMSCs with vector control. |
| 496 | 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. |
| 497 | 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. |
| 498 | 20618069 | Pancreatic islets contain low activities of catalase, selenium-dependent glutathione peroxidase 1 (GPX1), and Cu,Zn-superoxide dismutase 1 (SOD1). |
| 499 | 20618069 | While β cell-specific overexpression of Sod1 enhanced mouse resistance to streptozotocin-induced diabetes, the same manipulation of catalase aggravated onset of type 1 diabetes in nonobese diabetic mice. |
| 500 | 20618069 | Although knockouts of Gpx1 and Sod1 each alone or together decreased pancreatic β cell mass and plasma insulin concentrations, these knockouts improved body insulin sensitivity to different extents. |
| 501 | 20618069 | Pancreatic duodenal homeobox 1, forkhead box A2, and uncoupling protein 2 are three key regulators of β cell mass, insulin synthesis, and glucose-stimulated insulin secretion. |
| 502 | 20618069 | Phenotypes resulted from altering GPX1 and/or SOD1 were partly mediated through these factors, along with protein kinase B and c-jun terminal kinase. |
| 503 | 21152387 | Differentiated cells displayed increased Sox17 and Foxa2 expression consistent with definitive endoderm production. |
| 504 | 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. |
| 505 | 21292830 | Whereas only approximately 10% of binding sites are conserved, gene-centric analysis reveals that about 50% of genes with nearby TF occupancy are shared across species for both hepatic FOXA2 and adipocyte PPARγ. |
| 506 | 21623366 | Binding to nucleosomal DNA is critical for 'pioneer' transcription factors such as the winged-helix transcription factors Foxa1 and Foxa2 to regulate chromatin structure and gene activation. |
| 507 | 21623366 | By analyzing nucleosome occupancy and the distributions of heterochromatin protein 1 (Hp1), CBP (also known as Crebbp) and p300 (Ep300) in Foxa1- and Foxa2-deficient livers, we find that the maintenance of nucleosome position and chromatin structure surrounding Foxa2 binding sites is independent of Foxa1 and Foxa2. |
| 508 | 21623366 | Binding to nucleosomal DNA is critical for 'pioneer' transcription factors such as the winged-helix transcription factors Foxa1 and Foxa2 to regulate chromatin structure and gene activation. |
| 509 | 21623366 | By analyzing nucleosome occupancy and the distributions of heterochromatin protein 1 (Hp1), CBP (also known as Crebbp) and p300 (Ep300) in Foxa1- and Foxa2-deficient livers, we find that the maintenance of nucleosome position and chromatin structure surrounding Foxa2 binding sites is independent of Foxa1 and Foxa2. |
| 510 | 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. |
| 511 | 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. |
| 512 | 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. |
| 513 | 21829703 | Endocrine islets from mice with reduced Sox9 gene dosage exhibited normal glucose stimulated insulin secretion. |
| 514 | 21829703 | Our findings show Sox9 plays an important role in endocrine development by maintaining Ngn3 and Pdx1 expression. |
| 515 | 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. |
| 516 | 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. |
| 517 | 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. |
| 518 | 21829703 | Endocrine islets from mice with reduced Sox9 gene dosage exhibited normal glucose stimulated insulin secretion. |
| 519 | 21829703 | Our findings show Sox9 plays an important role in endocrine development by maintaining Ngn3 and Pdx1 expression. |
| 520 | 21841783 | Elevated concentrations of free fatty acids caused nuclear exclusion and reduced expression of the transcription factors FOXA2 and HNF1A in beta cells. |
| 521 | 21841783 | This resulted in a deficit of GnT-4a glycosyltransferase expression in beta cells that produced signs of metabolic disease, including hyperglycemia, impaired glucose tolerance, hyperinsulinemia, hepatic steatosis and diminished insulin action in muscle and adipose tissues. |
| 522 | 21855631 | In this study, we describe the roles of growth factors bFGF, BMP4 and Activin A in early hESC fate determination. |
| 523 | 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. |
| 524 | 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. |
| 525 | 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. |
| 526 | 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. |
| 527 | 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. |
| 528 | 21855631 | In this study, we describe the roles of growth factors bFGF, BMP4 and Activin A in early hESC fate determination. |
| 529 | 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. |
| 530 | 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. |
| 531 | 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. |
| 532 | 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. |
| 533 | 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. |
| 534 | 21855631 | In this study, we describe the roles of growth factors bFGF, BMP4 and Activin A in early hESC fate determination. |
| 535 | 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. |
| 536 | 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. |
| 537 | 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. |
| 538 | 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. |
| 539 | 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. |
| 540 | 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). |
| 541 | 22265403 | Foxa1 and Foxa2 are essential for sexual dimorphism in liver cancer. |
| 542 | 22265403 | Coregulation of target genes by Foxa1/a2 and either the estrogen receptor (ERα) or the androgen receptor (AR) was increased during hepatocarcinogenesis in normal female or male mice, respectively, but was lost in Foxa1/2-deficient mice. |
| 543 | 22737085 | Genome-wide location analysis reveals distinct transcriptional circuitry by paralogous regulators Foxa1 and Foxa2. |
| 544 | 22737085 | A potential path to functional relevance is mutation of the coding sequence leading to the acquisition of novel biochemical properties, as analyzed here for the highly homologous paralogs Foxa1 and Foxa2 transcriptional regulators. |
| 545 | 22737085 | We determine by genome-wide location analysis (ChIP-Seq) that, although Foxa1 and Foxa2 share a large fraction of binding sites in the liver, each protein also occupies distinct regulatory elements in vivo. |
| 546 | 22737085 | Foxa1-only sites are enriched for p53 binding sites and are frequently found near genes important to cell cycle regulation, while Foxa2-restricted sites show only a limited match to the forkhead consensus and are found in genes involved in steroid and lipid metabolism. |
| 547 | 22737085 | Thus, Foxa1 and Foxa2, while redundant during development, have evolved divergent roles in the adult liver, ensuring the maintenance of both genes during evolution. |
| 548 | 22737085 | Genome-wide location analysis reveals distinct transcriptional circuitry by paralogous regulators Foxa1 and Foxa2. |
| 549 | 22737085 | A potential path to functional relevance is mutation of the coding sequence leading to the acquisition of novel biochemical properties, as analyzed here for the highly homologous paralogs Foxa1 and Foxa2 transcriptional regulators. |
| 550 | 22737085 | We determine by genome-wide location analysis (ChIP-Seq) that, although Foxa1 and Foxa2 share a large fraction of binding sites in the liver, each protein also occupies distinct regulatory elements in vivo. |
| 551 | 22737085 | Foxa1-only sites are enriched for p53 binding sites and are frequently found near genes important to cell cycle regulation, while Foxa2-restricted sites show only a limited match to the forkhead consensus and are found in genes involved in steroid and lipid metabolism. |
| 552 | 22737085 | Thus, Foxa1 and Foxa2, while redundant during development, have evolved divergent roles in the adult liver, ensuring the maintenance of both genes during evolution. |
| 553 | 22737085 | Genome-wide location analysis reveals distinct transcriptional circuitry by paralogous regulators Foxa1 and Foxa2. |
| 554 | 22737085 | A potential path to functional relevance is mutation of the coding sequence leading to the acquisition of novel biochemical properties, as analyzed here for the highly homologous paralogs Foxa1 and Foxa2 transcriptional regulators. |
| 555 | 22737085 | We determine by genome-wide location analysis (ChIP-Seq) that, although Foxa1 and Foxa2 share a large fraction of binding sites in the liver, each protein also occupies distinct regulatory elements in vivo. |
| 556 | 22737085 | Foxa1-only sites are enriched for p53 binding sites and are frequently found near genes important to cell cycle regulation, while Foxa2-restricted sites show only a limited match to the forkhead consensus and are found in genes involved in steroid and lipid metabolism. |
| 557 | 22737085 | Thus, Foxa1 and Foxa2, while redundant during development, have evolved divergent roles in the adult liver, ensuring the maintenance of both genes during evolution. |
| 558 | 22737085 | Genome-wide location analysis reveals distinct transcriptional circuitry by paralogous regulators Foxa1 and Foxa2. |
| 559 | 22737085 | A potential path to functional relevance is mutation of the coding sequence leading to the acquisition of novel biochemical properties, as analyzed here for the highly homologous paralogs Foxa1 and Foxa2 transcriptional regulators. |
| 560 | 22737085 | We determine by genome-wide location analysis (ChIP-Seq) that, although Foxa1 and Foxa2 share a large fraction of binding sites in the liver, each protein also occupies distinct regulatory elements in vivo. |
| 561 | 22737085 | Foxa1-only sites are enriched for p53 binding sites and are frequently found near genes important to cell cycle regulation, while Foxa2-restricted sites show only a limited match to the forkhead consensus and are found in genes involved in steroid and lipid metabolism. |
| 562 | 22737085 | Thus, Foxa1 and Foxa2, while redundant during development, have evolved divergent roles in the adult liver, ensuring the maintenance of both genes during evolution. |
| 563 | 22737085 | Genome-wide location analysis reveals distinct transcriptional circuitry by paralogous regulators Foxa1 and Foxa2. |
| 564 | 22737085 | A potential path to functional relevance is mutation of the coding sequence leading to the acquisition of novel biochemical properties, as analyzed here for the highly homologous paralogs Foxa1 and Foxa2 transcriptional regulators. |
| 565 | 22737085 | We determine by genome-wide location analysis (ChIP-Seq) that, although Foxa1 and Foxa2 share a large fraction of binding sites in the liver, each protein also occupies distinct regulatory elements in vivo. |
| 566 | 22737085 | Foxa1-only sites are enriched for p53 binding sites and are frequently found near genes important to cell cycle regulation, while Foxa2-restricted sites show only a limited match to the forkhead consensus and are found in genes involved in steroid and lipid metabolism. |
| 567 | 22737085 | Thus, Foxa1 and Foxa2, while redundant during development, have evolved divergent roles in the adult liver, ensuring the maintenance of both genes during evolution. |
| 568 | 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. |
| 569 | 22841397 | The mRNA abundance of glucokinase, Cacna1d, acetyl-CoA carboxylase, and insulin also increased. |
| 570 | 23183535 | Global gene expression profiles, pluripotency expression patterns, and the capacity to differentiate into SOX17- and FOXA2-positive definitive endoderm (DE)-like cells were comparable among individual iPS clones. |
| 571 | 23183535 | However, notable intrapatient variation was evident upon further guided differentiation into HNF4α- and HNF1β-expressing primitive gut tube, and INS- and glucagon (GCG)-expressing islet-like cells. |
| 572 | 23471965 | Neurogenin3 cooperates with Foxa2 to autoactivate its own expression. |
| 573 | 23471965 | Additionally, we show that the broadly expressed endodermal forkhead factors Foxa1 and Foxa2 can cooperate synergistically to amplify Neurogenin3 autoregulation in vitro. |
| 574 | 23471965 | However, only Foxa2 colocalizes with Neurogenin3 in pancreatic progenitors, thus indicating a primary role for this factor in regulating Neurogenin3 expression in vivo. |
| 575 | 23471965 | Furthermore, in addition to decreasing Neurog3 autoregulation, inhibition of Foxa2 by RNA interference attenuates Neurogenin3-dependent activation of the endocrine developmental program in cultured duct mPAC cells. |
| 576 | 23471965 | Hence, these data uncover the potential functional cooperation between the endocrine lineage-determining factor Neurogenin3 and the widespread endoderm progenitor factor Foxa2 in the implementation of the endocrine developmental program in the pancreas. |
| 577 | 23471965 | Neurogenin3 cooperates with Foxa2 to autoactivate its own expression. |
| 578 | 23471965 | Additionally, we show that the broadly expressed endodermal forkhead factors Foxa1 and Foxa2 can cooperate synergistically to amplify Neurogenin3 autoregulation in vitro. |
| 579 | 23471965 | However, only Foxa2 colocalizes with Neurogenin3 in pancreatic progenitors, thus indicating a primary role for this factor in regulating Neurogenin3 expression in vivo. |
| 580 | 23471965 | Furthermore, in addition to decreasing Neurog3 autoregulation, inhibition of Foxa2 by RNA interference attenuates Neurogenin3-dependent activation of the endocrine developmental program in cultured duct mPAC cells. |
| 581 | 23471965 | Hence, these data uncover the potential functional cooperation between the endocrine lineage-determining factor Neurogenin3 and the widespread endoderm progenitor factor Foxa2 in the implementation of the endocrine developmental program in the pancreas. |
| 582 | 23471965 | Neurogenin3 cooperates with Foxa2 to autoactivate its own expression. |
| 583 | 23471965 | Additionally, we show that the broadly expressed endodermal forkhead factors Foxa1 and Foxa2 can cooperate synergistically to amplify Neurogenin3 autoregulation in vitro. |
| 584 | 23471965 | However, only Foxa2 colocalizes with Neurogenin3 in pancreatic progenitors, thus indicating a primary role for this factor in regulating Neurogenin3 expression in vivo. |
| 585 | 23471965 | Furthermore, in addition to decreasing Neurog3 autoregulation, inhibition of Foxa2 by RNA interference attenuates Neurogenin3-dependent activation of the endocrine developmental program in cultured duct mPAC cells. |
| 586 | 23471965 | Hence, these data uncover the potential functional cooperation between the endocrine lineage-determining factor Neurogenin3 and the widespread endoderm progenitor factor Foxa2 in the implementation of the endocrine developmental program in the pancreas. |
| 587 | 23471965 | Neurogenin3 cooperates with Foxa2 to autoactivate its own expression. |
| 588 | 23471965 | Additionally, we show that the broadly expressed endodermal forkhead factors Foxa1 and Foxa2 can cooperate synergistically to amplify Neurogenin3 autoregulation in vitro. |
| 589 | 23471965 | However, only Foxa2 colocalizes with Neurogenin3 in pancreatic progenitors, thus indicating a primary role for this factor in regulating Neurogenin3 expression in vivo. |
| 590 | 23471965 | Furthermore, in addition to decreasing Neurog3 autoregulation, inhibition of Foxa2 by RNA interference attenuates Neurogenin3-dependent activation of the endocrine developmental program in cultured duct mPAC cells. |
| 591 | 23471965 | Hence, these data uncover the potential functional cooperation between the endocrine lineage-determining factor Neurogenin3 and the widespread endoderm progenitor factor Foxa2 in the implementation of the endocrine developmental program in the pancreas. |
| 592 | 23471965 | Neurogenin3 cooperates with Foxa2 to autoactivate its own expression. |
| 593 | 23471965 | Additionally, we show that the broadly expressed endodermal forkhead factors Foxa1 and Foxa2 can cooperate synergistically to amplify Neurogenin3 autoregulation in vitro. |
| 594 | 23471965 | However, only Foxa2 colocalizes with Neurogenin3 in pancreatic progenitors, thus indicating a primary role for this factor in regulating Neurogenin3 expression in vivo. |
| 595 | 23471965 | Furthermore, in addition to decreasing Neurog3 autoregulation, inhibition of Foxa2 by RNA interference attenuates Neurogenin3-dependent activation of the endocrine developmental program in cultured duct mPAC cells. |
| 596 | 23471965 | Hence, these data uncover the potential functional cooperation between the endocrine lineage-determining factor Neurogenin3 and the widespread endoderm progenitor factor Foxa2 in the implementation of the endocrine developmental program in the pancreas. |
| 597 | 23828045 | At 1 week after multiple low-dose STZ administrations, pancreatic β-cells showed impaired insulin expression, while maintaining expression of nuclear Nkx6.1. |
| 598 | 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). |
| 599 | 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. |
| 600 | 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. |
| 601 | 23828045 | Upon pancreatic GLP-1 expression, upregulation of Cxcl13 and Nptx2 was observed in STZ-damaged islets, but not in untreated normal islets. |
| 602 | 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. |
| 603 | 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. |