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Gene Information
Gene symbol: HNF4A
Gene name: hepatocyte nuclear factor 4, alpha
HGNC ID: 5024
Synonyms: NR2A1, HNF4
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 1446805 | Recently, linkage between the ADA gene locus and MODY, a subtype of NIDDM, has been reported. |
| 2 | 1628771 | No linkage to ADA or GLUT2 genes in two families. |
| 3 | 1628771 | We studied the linkage of MODY to two loci: ADA and GLUT2 in two large pedigrees with nonradioactive microsatellite polymorphic systems. |
| 4 | 1628771 | Formal linkage analysis excluded a tight linkage between ADA and MODY with a LOD score of -5.82 and -2.24 at a recombination fraction of 0.01 in the two families. |
| 5 | 1628771 | The LOD scores for GLUT2 were -7.79 and -1.9 at a recombination fraction of 0.001 in the two families, thus providing evidence against the involvement of GLUT2 in MODY. |
| 6 | 1628771 | No linkage to ADA or GLUT2 genes in two families. |
| 7 | 1628771 | We studied the linkage of MODY to two loci: ADA and GLUT2 in two large pedigrees with nonradioactive microsatellite polymorphic systems. |
| 8 | 1628771 | Formal linkage analysis excluded a tight linkage between ADA and MODY with a LOD score of -5.82 and -2.24 at a recombination fraction of 0.01 in the two families. |
| 9 | 1628771 | The LOD scores for GLUT2 were -7.79 and -1.9 at a recombination fraction of 0.001 in the two families, thus providing evidence against the involvement of GLUT2 in MODY. |
| 10 | 1779465 | Using the strategy of the second approach, Bell et al. recently reported that the gene responsible for MODY (maturity-onset diabetes of the young) is tightly linked to the adenosine deaminase gene on chromosome 20q. |
| 11 | 1899928 | Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent diabetes mellitus characterized by an early age of onset, usually before 25 years of age, and an autosomal dominant mode of inheritance. |
| 12 | 1899928 | A DNA polymorphism in the adenosine deaminase gene (ADA) on the long arm of chromosome 20 was found to cosegregate with MODY. |
| 13 | 1899928 | The maximum logarithm of odds (lod score) for linkage between MODY and ADA was 5.25 at a recombination fraction of 0.00. |
| 14 | 1899928 | These results indicate that the odds are greater than 178,000:1 that the gene responsible for MODY in this family is tightly linked to the ADA gene on chromosome 20q. |
| 15 | 1899928 | Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent diabetes mellitus characterized by an early age of onset, usually before 25 years of age, and an autosomal dominant mode of inheritance. |
| 16 | 1899928 | A DNA polymorphism in the adenosine deaminase gene (ADA) on the long arm of chromosome 20 was found to cosegregate with MODY. |
| 17 | 1899928 | The maximum logarithm of odds (lod score) for linkage between MODY and ADA was 5.25 at a recombination fraction of 0.00. |
| 18 | 1899928 | These results indicate that the odds are greater than 178,000:1 that the gene responsible for MODY in this family is tightly linked to the ADA gene on chromosome 20q. |
| 19 | 1899928 | Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent diabetes mellitus characterized by an early age of onset, usually before 25 years of age, and an autosomal dominant mode of inheritance. |
| 20 | 1899928 | A DNA polymorphism in the adenosine deaminase gene (ADA) on the long arm of chromosome 20 was found to cosegregate with MODY. |
| 21 | 1899928 | The maximum logarithm of odds (lod score) for linkage between MODY and ADA was 5.25 at a recombination fraction of 0.00. |
| 22 | 1899928 | These results indicate that the odds are greater than 178,000:1 that the gene responsible for MODY in this family is tightly linked to the ADA gene on chromosome 20q. |
| 23 | 1899928 | Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent diabetes mellitus characterized by an early age of onset, usually before 25 years of age, and an autosomal dominant mode of inheritance. |
| 24 | 1899928 | A DNA polymorphism in the adenosine deaminase gene (ADA) on the long arm of chromosome 20 was found to cosegregate with MODY. |
| 25 | 1899928 | The maximum logarithm of odds (lod score) for linkage between MODY and ADA was 5.25 at a recombination fraction of 0.00. |
| 26 | 1899928 | These results indicate that the odds are greater than 178,000:1 that the gene responsible for MODY in this family is tightly linked to the ADA gene on chromosome 20q. |
| 27 | 3289993 | Insulin action and insulin secretion in identical twins with MODY. |
| 28 | 3289993 | Differences in insulin secretion pattern and/or insulin action between the twins is supposed to be responsible for development of hyperglycemia in MODY. |
| 29 | 3289993 | On the other hand, identical defects in insulin secretion and action in the twins may point to the primary genetic defect in MODY. |
| 30 | 3289993 | Insulin action and insulin secretion in identical twins with MODY. |
| 31 | 3289993 | Differences in insulin secretion pattern and/or insulin action between the twins is supposed to be responsible for development of hyperglycemia in MODY. |
| 32 | 3289993 | On the other hand, identical defects in insulin secretion and action in the twins may point to the primary genetic defect in MODY. |
| 33 | 3289993 | Insulin action and insulin secretion in identical twins with MODY. |
| 34 | 3289993 | Differences in insulin secretion pattern and/or insulin action between the twins is supposed to be responsible for development of hyperglycemia in MODY. |
| 35 | 3289993 | On the other hand, identical defects in insulin secretion and action in the twins may point to the primary genetic defect in MODY. |
| 36 | 3882370 | Pancreatic beta cell responses were measured in obese and nonobese maturity-onset diabetes of the young (MODY) patients by estimating serum immunoreactive insulin (IRI) and C-peptide (CP) during oral glucose tolerance testing (OGTT). |
| 37 | 3882370 | This is suggestive of altered metabolic fates of insulin and CP in the MODY patients. |
| 38 | 3882370 | Pancreatic beta cell responses were measured in obese and nonobese maturity-onset diabetes of the young (MODY) patients by estimating serum immunoreactive insulin (IRI) and C-peptide (CP) during oral glucose tolerance testing (OGTT). |
| 39 | 3882370 | This is suggestive of altered metabolic fates of insulin and CP in the MODY patients. |
| 40 | 3907232 | Ultrasonography was performed in three groups of young diabetics in the tropics, namely MODY, IDDM and tropical pancreatic diabetes (TPD). |
| 41 | 3907232 | MODY and IDDM patients did not show any significant changes except a slight reduction in size of the gland. |
| 42 | 3907232 | Ultrasonography was performed in three groups of young diabetics in the tropics, namely MODY, IDDM and tropical pancreatic diabetes (TPD). |
| 43 | 3907232 | MODY and IDDM patients did not show any significant changes except a slight reduction in size of the gland. |
| 44 | 7508874 | Maturity-onset diabetes of the young (MODY) is a model for genetic studies of non-insulin-dependent diabetes mellitus. |
| 45 | 7508874 | We have identified 15 MODY families in which diabetes is not the result of mutations in the glucokinase gene. |
| 46 | 7508874 | Nine other candidate genes potentially implicated in insulin secretion or insulin action have been tested for linkage with MODY in these families, including glucokinase regulatory protein, hexokinase II, insulin receptor substrate 1, fatty acid-binding protein 2, glucagon-like peptide-1 receptor, apolipoprotein C-II, glycogen synthase, adenosine deaminase (a marker for the MODY gene on chromosome 20), and phosphoenolpyruvate carboxykinase. |
| 47 | 7508874 | Maturity-onset diabetes of the young (MODY) is a model for genetic studies of non-insulin-dependent diabetes mellitus. |
| 48 | 7508874 | We have identified 15 MODY families in which diabetes is not the result of mutations in the glucokinase gene. |
| 49 | 7508874 | Nine other candidate genes potentially implicated in insulin secretion or insulin action have been tested for linkage with MODY in these families, including glucokinase regulatory protein, hexokinase II, insulin receptor substrate 1, fatty acid-binding protein 2, glucagon-like peptide-1 receptor, apolipoprotein C-II, glycogen synthase, adenosine deaminase (a marker for the MODY gene on chromosome 20), and phosphoenolpyruvate carboxykinase. |
| 50 | 7508874 | Maturity-onset diabetes of the young (MODY) is a model for genetic studies of non-insulin-dependent diabetes mellitus. |
| 51 | 7508874 | We have identified 15 MODY families in which diabetes is not the result of mutations in the glucokinase gene. |
| 52 | 7508874 | Nine other candidate genes potentially implicated in insulin secretion or insulin action have been tested for linkage with MODY in these families, including glucokinase regulatory protein, hexokinase II, insulin receptor substrate 1, fatty acid-binding protein 2, glucagon-like peptide-1 receptor, apolipoprotein C-II, glycogen synthase, adenosine deaminase (a marker for the MODY gene on chromosome 20), and phosphoenolpyruvate carboxykinase. |
| 53 | 7589847 | Maturity-onset diabetes of the young (MODY) is a heterogeneous disorder that appears to be characterized by a primary defect in insulin secretion. |
| 54 | 7589847 | Mutations in an unknown locus (MODY1) on chromosome 20 and the glucokinase gene (MODY2) on chromosome 7 can cause this form of non-insulin-dependent diabetes. |
| 55 | 7589847 | Maturity-onset diabetes of the young (MODY) is a heterogeneous disorder that appears to be characterized by a primary defect in insulin secretion. |
| 56 | 7589847 | Mutations in an unknown locus (MODY1) on chromosome 20 and the glucokinase gene (MODY2) on chromosome 7 can cause this form of non-insulin-dependent diabetes. |
| 57 | 7789637 | Subjects who have maturity-onset diabetes of the young (MODY) due to mutations in the glucokinase gene demonstrate different patterns of altered insulin secretion when compared with subjects who have mutations in the MODY1 gene on chromosome 20. |
| 58 | 7789637 | In contrast, mutations in the MODY1 gene are associated with an inability to increase insulin secretion as the plasma glucose concentration increases above 7-8 mmol/l and the normal priming effect of glucose on insulin secretion is lost. |
| 59 | 7789637 | These characteristics of the dose-response relationships between glucose and insulin secretion result in a more severe degree of hyperglycemia than observed in subjects with glucokinase mutations, and these subjects more frequently need insulin treatment. |
| 60 | 7789637 | Subjects who have maturity-onset diabetes of the young (MODY) due to mutations in the glucokinase gene demonstrate different patterns of altered insulin secretion when compared with subjects who have mutations in the MODY1 gene on chromosome 20. |
| 61 | 7789637 | In contrast, mutations in the MODY1 gene are associated with an inability to increase insulin secretion as the plasma glucose concentration increases above 7-8 mmol/l and the normal priming effect of glucose on insulin secretion is lost. |
| 62 | 7789637 | These characteristics of the dose-response relationships between glucose and insulin secretion result in a more severe degree of hyperglycemia than observed in subjects with glucokinase mutations, and these subjects more frequently need insulin treatment. |
| 63 | 7789636 | Altered insulin secretory responses to glucose in subjects with a mutation in the MODY1 gene on chromosome 20. |
| 64 | 7789636 | This study was undertaken to test the hypothesis that the diabetes susceptibility gene on chromosome 20q12 responsible for maturity-onset diabetes of the young (MODY) in a large kindred, the RW family, results in characteristic alterations in the dose-response relationships between plasma glucose concentration and insulin secretion rate (ISR) that differentiate this form of MODY from MODY in subjects with glucokinase mutations. |
| 65 | 7789636 | Altered insulin secretory responses to glucose in subjects with a mutation in the MODY1 gene on chromosome 20. |
| 66 | 7789636 | This study was undertaken to test the hypothesis that the diabetes susceptibility gene on chromosome 20q12 responsible for maturity-onset diabetes of the young (MODY) in a large kindred, the RW family, results in characteristic alterations in the dose-response relationships between plasma glucose concentration and insulin secretion rate (ISR) that differentiate this form of MODY from MODY in subjects with glucokinase mutations. |
| 67 | 7951673 | So far, two MODY susceptibility loci have been reported, one unknown gene on chromosome 20q, and glucokinase on chromosome 7q. |
| 68 | 7951673 | Glucokinase mutations appear to be the most common cause of MODY in the European population, being found in 60% of the families investigated. |
| 69 | 7951673 | So far, two MODY susceptibility loci have been reported, one unknown gene on chromosome 20q, and glucokinase on chromosome 7q. |
| 70 | 7951673 | Glucokinase mutations appear to be the most common cause of MODY in the European population, being found in 60% of the families investigated. |
| 71 | 8035658 | MODY is also linked to the glucokinase gene on chromosome 7p and many different mutations associated with MODY have been identified in this gene. |
| 72 | 8035658 | MODY due to mutations in the glucokinase gene is a relatively mild form of diabetes with mild fasting hyperglycemia and IGT in the majority. |
| 73 | 8035658 | Clinical studies indicate that the genetic or primary defect in MODY is characterized by deranged and deficient insulin secretion and not by insulin resistance and that there are quantitative and qualitative differences in insulin secretory defects which differentiate subjects with MODY due to glucokinase mutations from those with mutations in the gene on chromosome 20q. |
| 74 | 8035658 | MODY is also linked to the glucokinase gene on chromosome 7p and many different mutations associated with MODY have been identified in this gene. |
| 75 | 8035658 | MODY due to mutations in the glucokinase gene is a relatively mild form of diabetes with mild fasting hyperglycemia and IGT in the majority. |
| 76 | 8035658 | Clinical studies indicate that the genetic or primary defect in MODY is characterized by deranged and deficient insulin secretion and not by insulin resistance and that there are quantitative and qualitative differences in insulin secretory defects which differentiate subjects with MODY due to glucokinase mutations from those with mutations in the gene on chromosome 20q. |
| 77 | 8035658 | MODY is also linked to the glucokinase gene on chromosome 7p and many different mutations associated with MODY have been identified in this gene. |
| 78 | 8035658 | MODY due to mutations in the glucokinase gene is a relatively mild form of diabetes with mild fasting hyperglycemia and IGT in the majority. |
| 79 | 8035658 | Clinical studies indicate that the genetic or primary defect in MODY is characterized by deranged and deficient insulin secretion and not by insulin resistance and that there are quantitative and qualitative differences in insulin secretory defects which differentiate subjects with MODY due to glucokinase mutations from those with mutations in the gene on chromosome 20q. |
| 80 | 8168652 | Six mutations in the glucokinase gene identified in MODY by using a nonradioactive sensitive screening technique. |
| 81 | 8168652 | We have reported that 56% of French families with maturity-onset diabetes of the young (MODY) carry a mutation in the glucokinase gene (GCK). |
| 82 | 8168652 | All six families carrying a mutation in GCK were typical MODY and most of their affected members had a mild form of diabetes. |
| 83 | 8168652 | Six mutations in the glucokinase gene identified in MODY by using a nonradioactive sensitive screening technique. |
| 84 | 8168652 | We have reported that 56% of French families with maturity-onset diabetes of the young (MODY) carry a mutation in the glucokinase gene (GCK). |
| 85 | 8168652 | All six families carrying a mutation in GCK were typical MODY and most of their affected members had a mild form of diabetes. |
| 86 | 8168652 | Six mutations in the glucokinase gene identified in MODY by using a nonradioactive sensitive screening technique. |
| 87 | 8168652 | We have reported that 56% of French families with maturity-onset diabetes of the young (MODY) carry a mutation in the glucokinase gene (GCK). |
| 88 | 8168652 | All six families carrying a mutation in GCK were typical MODY and most of their affected members had a mild form of diabetes. |
| 89 | 8621016 | Thus, mutations involving the genes for GIRK1 or FAD-glycerophosphate dehydrogenase are unlikely to cause MODY, and a common mutation in either gene is unlikely to contribute to NIDDM in whites. |
| 90 | 8632993 | We have generated a physical map of human chromosome bands 20q11.2-20q13.1, a region containing a gene involved in the development of one form of early-onset, non-insulin-dependent diabetes mellitus, MODY1, as well as a putative myeloid tumor suppressor gene. |
| 91 | 8866553 | Altered insulin secretory responses to glucose in diabetic and nondiabetic subjects with mutations in the diabetes susceptibility gene MODY3 on chromosome 12. |
| 92 | 8866553 | One form of maturity-onset diabetes of the young (MODY) results from mutations in a gene, designated MODY3, located on chromosome 12 in band q24. |
| 93 | 8866553 | The present study was undertaken to define the interactions between glucose and insulin secretion rate (ISR) in subjects with mutations in MODY3. |
| 94 | 8866553 | Of the 13 MODY3 subjects, six subjects with normal fasting glucose and glycosylated hemoglobin and seven overtly diabetic subjects were studied as were six nondiabetic control subjects. |
| 95 | 8866553 | Basal glucose levels were higher and insulin levels were lower in MODY3 subjects with diabetes compared with nondiabetic subjects or with normal healthy control subjects. |
| 96 | 8866553 | Administration of glucose by intravenous infusion for 42 h resulted in a significant increase in the amount of insulin secreted over the 5-9 mmol/l glucose concentration range in the control subjects and nondiabetic MODY3 subjects (by 38 and 35%, respectively), but no significant change was observed in the diabetic MODY3 subjects. |
| 97 | 8866553 | In conclusion, in nondiabetic MODY3 subjects insulin secretion demonstrates a diminished ability to respond when blood glucose exceeds 8 mmol/l. |
| 98 | 8866553 | The defect in insulin secretion in the nondiabetic MODY3 subjects differs from that reported previously in nondiabetic MODY1 or mildly diabetic MODY2 subjects. |
| 99 | 8866553 | Altered insulin secretory responses to glucose in diabetic and nondiabetic subjects with mutations in the diabetes susceptibility gene MODY3 on chromosome 12. |
| 100 | 8866553 | One form of maturity-onset diabetes of the young (MODY) results from mutations in a gene, designated MODY3, located on chromosome 12 in band q24. |
| 101 | 8866553 | The present study was undertaken to define the interactions between glucose and insulin secretion rate (ISR) in subjects with mutations in MODY3. |
| 102 | 8866553 | Of the 13 MODY3 subjects, six subjects with normal fasting glucose and glycosylated hemoglobin and seven overtly diabetic subjects were studied as were six nondiabetic control subjects. |
| 103 | 8866553 | Basal glucose levels were higher and insulin levels were lower in MODY3 subjects with diabetes compared with nondiabetic subjects or with normal healthy control subjects. |
| 104 | 8866553 | Administration of glucose by intravenous infusion for 42 h resulted in a significant increase in the amount of insulin secreted over the 5-9 mmol/l glucose concentration range in the control subjects and nondiabetic MODY3 subjects (by 38 and 35%, respectively), but no significant change was observed in the diabetic MODY3 subjects. |
| 105 | 8866553 | In conclusion, in nondiabetic MODY3 subjects insulin secretion demonstrates a diminished ability to respond when blood glucose exceeds 8 mmol/l. |
| 106 | 8866553 | The defect in insulin secretion in the nondiabetic MODY3 subjects differs from that reported previously in nondiabetic MODY1 or mildly diabetic MODY2 subjects. |
| 107 | 8945471 | The disease maturity-onset diabetes of the young (MODY) is a genetically heterogeneous monogenic form of non-insulin-dependent (type 2) diabetes mellitus (NIDDM), characterized by early onset, usually before 25 years of age and often in adolescence or childhood, and by autosomal dominant inheritance. |
| 108 | 8945471 | Clinical studies have shown that prediabetic MODY subjects have normal insulin sensitivity but suffer from a defect in glucose-stimulated insulin secretion, suggesting that pancreatic beta-cell dysfunction rather than insulin resistance is the primary defect in this disorder. |
| 109 | 8945471 | Linkage studies have localized the genes that are mutated in MODY on human chromosomes 20 (MODY1), 7 (MODY2) and 12 (MODY3), with MODY2 and MODY3 being allelic with the genes encoding glucokinase, a key regulator of insulin secretion, and hepatocyte nuclear factor-1alpha (HNF-1alpha), a transcription factor involved in tissue-specific regulation of liver genes but also expressed in pancreatic islets, insulinoma cells and other tissues. |
| 110 | 8945471 | The disease maturity-onset diabetes of the young (MODY) is a genetically heterogeneous monogenic form of non-insulin-dependent (type 2) diabetes mellitus (NIDDM), characterized by early onset, usually before 25 years of age and often in adolescence or childhood, and by autosomal dominant inheritance. |
| 111 | 8945471 | Clinical studies have shown that prediabetic MODY subjects have normal insulin sensitivity but suffer from a defect in glucose-stimulated insulin secretion, suggesting that pancreatic beta-cell dysfunction rather than insulin resistance is the primary defect in this disorder. |
| 112 | 8945471 | Linkage studies have localized the genes that are mutated in MODY on human chromosomes 20 (MODY1), 7 (MODY2) and 12 (MODY3), with MODY2 and MODY3 being allelic with the genes encoding glucokinase, a key regulator of insulin secretion, and hepatocyte nuclear factor-1alpha (HNF-1alpha), a transcription factor involved in tissue-specific regulation of liver genes but also expressed in pancreatic islets, insulinoma cells and other tissues. |
| 113 | 8945471 | The disease maturity-onset diabetes of the young (MODY) is a genetically heterogeneous monogenic form of non-insulin-dependent (type 2) diabetes mellitus (NIDDM), characterized by early onset, usually before 25 years of age and often in adolescence or childhood, and by autosomal dominant inheritance. |
| 114 | 8945471 | Clinical studies have shown that prediabetic MODY subjects have normal insulin sensitivity but suffer from a defect in glucose-stimulated insulin secretion, suggesting that pancreatic beta-cell dysfunction rather than insulin resistance is the primary defect in this disorder. |
| 115 | 8945471 | Linkage studies have localized the genes that are mutated in MODY on human chromosomes 20 (MODY1), 7 (MODY2) and 12 (MODY3), with MODY2 and MODY3 being allelic with the genes encoding glucokinase, a key regulator of insulin secretion, and hepatocyte nuclear factor-1alpha (HNF-1alpha), a transcription factor involved in tissue-specific regulation of liver genes but also expressed in pancreatic islets, insulinoma cells and other tissues. |
| 116 | 8945470 | MODY genes have been localized to chromosomes 7, 12 and 20 (refs 5, 7, 8) and clinical studies indicate that mutations in these genes are associated with abnormal patterns of glucose-stimulated insulin secretion. |
| 117 | 8945470 | HNF-1alpha is a transcription factor that helps in the tissue-specific regulation of the expression of several liver genes and also functions as a weak transactivator of the rat insulin-I gene. |
| 118 | 9029679 | Hepatocyte nuclear factor-4 alpha gene mutations in Japanese non-insulin dependent diabetes mellitus (NIDDM) patients. |
| 119 | 9032114 | We have also identified the mutation in the HNF-1alpha gene in the Jutland pedigree, one of the original MODY pedigrees reported in the literature, as being a T-->G substitution in codon 241, resulting in the replacement of a conserved Cys by Gly (C241G). |
| 120 | 9075818 | MODY families for mutations in the coding region of the HNF-1alpha gene. |
| 121 | 9075818 | We have demonstrated that mutations in the HNF-1alpha gene are a common cause of MODY in U.K. families and result in early onset NIDDM with a progressive clinical course. |
| 122 | 9075818 | MODY families for mutations in the coding region of the HNF-1alpha gene. |
| 123 | 9075818 | We have demonstrated that mutations in the HNF-1alpha gene are a common cause of MODY in U.K. families and result in early onset NIDDM with a progressive clinical course. |
| 124 | 9075819 | The primary objective of the present study was to search for genetic variation in the HNF-1alpha gene in nine nonrelated Danish Caucasian subjects with MODY. |
| 125 | 9075819 | Direct sequencing of the coding region and intron-exon boundaries of the HNF-1alpha gene revealed 2 novel and 1 previously reported missense mutations and 2 novel frameshift mutations in five of nine MODY subjects. |
| 126 | 9075819 | In conclusion, 1) mutations in the HNF-1alpha gene are common in Danish Caucasian MODY patients, and 2) early stages in the pathogenesis of MODY3 caused by the P447L mutation may be characterized by a hyperexcitability of beta-cells to intravenous secretagogues. |
| 127 | 9075819 | The primary objective of the present study was to search for genetic variation in the HNF-1alpha gene in nine nonrelated Danish Caucasian subjects with MODY. |
| 128 | 9075819 | Direct sequencing of the coding region and intron-exon boundaries of the HNF-1alpha gene revealed 2 novel and 1 previously reported missense mutations and 2 novel frameshift mutations in five of nine MODY subjects. |
| 129 | 9075819 | In conclusion, 1) mutations in the HNF-1alpha gene are common in Danish Caucasian MODY patients, and 2) early stages in the pathogenesis of MODY3 caused by the P447L mutation may be characterized by a hyperexcitability of beta-cells to intravenous secretagogues. |
| 130 | 9075819 | The primary objective of the present study was to search for genetic variation in the HNF-1alpha gene in nine nonrelated Danish Caucasian subjects with MODY. |
| 131 | 9075819 | Direct sequencing of the coding region and intron-exon boundaries of the HNF-1alpha gene revealed 2 novel and 1 previously reported missense mutations and 2 novel frameshift mutations in five of nine MODY subjects. |
| 132 | 9075819 | In conclusion, 1) mutations in the HNF-1alpha gene are common in Danish Caucasian MODY patients, and 2) early stages in the pathogenesis of MODY3 caused by the P447L mutation may be characterized by a hyperexcitability of beta-cells to intravenous secretagogues. |
| 133 | 9097962 | Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous subtype of non-insulin-dependent diabetes mellitus (NIDDM) characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. |
| 134 | 9097962 | Recent studies have shown that mutations in the two functionally related transcription factors, hepatocyte nuclear factor 4 alpha (HNF-4alpha) and hepatocyte nuclear factor 1 alpha (HNF-1alpha) are associated with the MODY1 and MODY3 forms of diabetes respectively, whereas mutations in the enzyme glucokinase are the cause of the MODY2 form. |
| 135 | 9097962 | We have examined 10 unrelated Caucasian families in which MODY/NIDDM co-segregated with markers for MODY3 for mutations in the HNF-1alpha gene (TCF1). |
| 136 | 9097962 | Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous subtype of non-insulin-dependent diabetes mellitus (NIDDM) characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. |
| 137 | 9097962 | Recent studies have shown that mutations in the two functionally related transcription factors, hepatocyte nuclear factor 4 alpha (HNF-4alpha) and hepatocyte nuclear factor 1 alpha (HNF-1alpha) are associated with the MODY1 and MODY3 forms of diabetes respectively, whereas mutations in the enzyme glucokinase are the cause of the MODY2 form. |
| 138 | 9097962 | We have examined 10 unrelated Caucasian families in which MODY/NIDDM co-segregated with markers for MODY3 for mutations in the HNF-1alpha gene (TCF1). |
| 139 | 9097962 | Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous subtype of non-insulin-dependent diabetes mellitus (NIDDM) characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. |
| 140 | 9097962 | Recent studies have shown that mutations in the two functionally related transcription factors, hepatocyte nuclear factor 4 alpha (HNF-4alpha) and hepatocyte nuclear factor 1 alpha (HNF-1alpha) are associated with the MODY1 and MODY3 forms of diabetes respectively, whereas mutations in the enzyme glucokinase are the cause of the MODY2 form. |
| 141 | 9097962 | We have examined 10 unrelated Caucasian families in which MODY/NIDDM co-segregated with markers for MODY3 for mutations in the HNF-1alpha gene (TCF1). |
| 142 | 9105779 | In particular, monozygotic twin studies have indicated a higher rate of concordance in non-insulin-dependent (NIDDM) than in insulin-dependent diabetes mellitus (IDDM). |
| 143 | 9105779 | In IDDM, 8 susceptibility loci have been identified, notably the HLA complex and insulin promotor gene. |
| 144 | 9105779 | Rigorous family studies have identified monogenic subtypes representing 10-15% of all NIDDM: MODY2 related to glucokinase gene mutations, MODY1 and MODY3 secondary to mutation of hepatic nuclear factors, and diabetes resulting from deletion or mutation of mitochondrial DNA. |
| 145 | 9105779 | Finally, susceptibility genes for the increased severity and frequency of vascular complications have been identified, such as angiotensin converting enzyme, aldose reductase and aldehyde dehydrogenase genes. |
| 146 | 9133559 | Evidence for linkage to NIDDM was found with polymorphic loci that map to the long arms of human chromosomes 20 and 12 in regions containing the MODY1 and MODY3 genes. |
| 147 | 9133559 | No evidence for linkage of MODY1 and MODY3 markers to NIDDM in African-American sib pairs was observed. |
| 148 | 9133559 | In addition, no evidence for linkage to MODY2 (glucokinase-associated MODY) was observed with either study population. |
| 149 | 9133559 | The results suggest that genes contributing to NIDDM in the general Caucasian population are located in the regions containing the MODY1 and MODY3 genes. |
| 150 | 9133559 | Evidence for linkage to NIDDM was found with polymorphic loci that map to the long arms of human chromosomes 20 and 12 in regions containing the MODY1 and MODY3 genes. |
| 151 | 9133559 | No evidence for linkage of MODY1 and MODY3 markers to NIDDM in African-American sib pairs was observed. |
| 152 | 9133559 | In addition, no evidence for linkage to MODY2 (glucokinase-associated MODY) was observed with either study population. |
| 153 | 9133559 | The results suggest that genes contributing to NIDDM in the general Caucasian population are located in the regions containing the MODY1 and MODY3 genes. |
| 154 | 9133559 | Evidence for linkage to NIDDM was found with polymorphic loci that map to the long arms of human chromosomes 20 and 12 in regions containing the MODY1 and MODY3 genes. |
| 155 | 9133559 | No evidence for linkage of MODY1 and MODY3 markers to NIDDM in African-American sib pairs was observed. |
| 156 | 9133559 | In addition, no evidence for linkage to MODY2 (glucokinase-associated MODY) was observed with either study population. |
| 157 | 9133559 | The results suggest that genes contributing to NIDDM in the general Caucasian population are located in the regions containing the MODY1 and MODY3 genes. |
| 158 | 9133559 | Evidence for linkage to NIDDM was found with polymorphic loci that map to the long arms of human chromosomes 20 and 12 in regions containing the MODY1 and MODY3 genes. |
| 159 | 9133559 | No evidence for linkage of MODY1 and MODY3 markers to NIDDM in African-American sib pairs was observed. |
| 160 | 9133559 | In addition, no evidence for linkage to MODY2 (glucokinase-associated MODY) was observed with either study population. |
| 161 | 9133559 | The results suggest that genes contributing to NIDDM in the general Caucasian population are located in the regions containing the MODY1 and MODY3 genes. |
| 162 | 9162575 | Maturity-onset diabetes of the young (MODY), MODY genes and non-insulin-dependent diabetes mellitus. |
| 163 | 9162575 | Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of non-insulin-dependent diabetes mellitus (NIDDM) characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. |
| 164 | 9162575 | To date, three MODY genes have been identified on chromosomes 20q [hepatocyte nuclear factor (HNF-4 alpha)/MODY1], 7p (glucokinase/MODY2) and 12q (HNF-1 alpha/MODY3). |
| 165 | 9162575 | In contrast, MODY1 and MODY3 are characterised by severe insulin secretory defects and major hyperglycaemia associated with microvascular complications. |
| 166 | 9162575 | Maturity-onset diabetes of the young (MODY), MODY genes and non-insulin-dependent diabetes mellitus. |
| 167 | 9162575 | Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of non-insulin-dependent diabetes mellitus (NIDDM) characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. |
| 168 | 9162575 | To date, three MODY genes have been identified on chromosomes 20q [hepatocyte nuclear factor (HNF-4 alpha)/MODY1], 7p (glucokinase/MODY2) and 12q (HNF-1 alpha/MODY3). |
| 169 | 9162575 | In contrast, MODY1 and MODY3 are characterised by severe insulin secretory defects and major hyperglycaemia associated with microvascular complications. |
| 170 | 9162575 | Maturity-onset diabetes of the young (MODY), MODY genes and non-insulin-dependent diabetes mellitus. |
| 171 | 9162575 | Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of non-insulin-dependent diabetes mellitus (NIDDM) characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. |
| 172 | 9162575 | To date, three MODY genes have been identified on chromosomes 20q [hepatocyte nuclear factor (HNF-4 alpha)/MODY1], 7p (glucokinase/MODY2) and 12q (HNF-1 alpha/MODY3). |
| 173 | 9162575 | In contrast, MODY1 and MODY3 are characterised by severe insulin secretory defects and major hyperglycaemia associated with microvascular complications. |
| 174 | 9162575 | Maturity-onset diabetes of the young (MODY), MODY genes and non-insulin-dependent diabetes mellitus. |
| 175 | 9162575 | Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of non-insulin-dependent diabetes mellitus (NIDDM) characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. |
| 176 | 9162575 | To date, three MODY genes have been identified on chromosomes 20q [hepatocyte nuclear factor (HNF-4 alpha)/MODY1], 7p (glucokinase/MODY2) and 12q (HNF-1 alpha/MODY3). |
| 177 | 9162575 | In contrast, MODY1 and MODY3 are characterised by severe insulin secretory defects and major hyperglycaemia associated with microvascular complications. |
| 178 | 9231664 | The genes encoding the functionally related hepatocyte nuclear factors HNF-1alpha and HNF-4alpha play a critical role in normal pancreatic beta-cell function. |
| 179 | 9231664 | Mutations in these liver-enriched transcription factors result in two forms of early-onset type 2 diabetes (maturity-onset diabetes of the young [MODY]), MODY3 and MODY1, which are characterized by impaired glucose-stimulated insulin secretion, early disease onset, and autosomal dominant inheritance. |
| 180 | 9231664 | We report the identification and characterization of simple tandem repeat DNA polymorphisms in the genes encoding HNF-3alpha, -3beta, -3gamma, -4gamma, and -6 and the mapping of HNF-6 to chromosome bands 15q21.1-21.2 by fluorescence in situ hybridization. |
| 181 | 9231664 | The genes encoding the functionally related hepatocyte nuclear factors HNF-1alpha and HNF-4alpha play a critical role in normal pancreatic beta-cell function. |
| 182 | 9231664 | Mutations in these liver-enriched transcription factors result in two forms of early-onset type 2 diabetes (maturity-onset diabetes of the young [MODY]), MODY3 and MODY1, which are characterized by impaired glucose-stimulated insulin secretion, early disease onset, and autosomal dominant inheritance. |
| 183 | 9231664 | We report the identification and characterization of simple tandem repeat DNA polymorphisms in the genes encoding HNF-3alpha, -3beta, -3gamma, -4gamma, and -6 and the mapping of HNF-6 to chromosome bands 15q21.1-21.2 by fluorescence in situ hybridization. |
| 184 | 9243109 | Maturity-onset diabetes of the young (MODY) is a monogenic subgroup of non-insulin dependent diabetes mellitus (NIDDM) characterised bylan early age of onset (< 25 years) and an autosomal dominant mode of inheritance. |
| 185 | 9243109 | MODY is genetically heterogeneous with three different genes identified to date; hepatocyte nuclear factor 4 alpha (HNF-4 alpha) [MODY1], glucokinase [MODY2] and hepatocyte nuclear factor 1 alpha (HNF-1 alpha) [MODY3]. |
| 186 | 9243109 | Maturity-onset diabetes of the young (MODY) is a monogenic subgroup of non-insulin dependent diabetes mellitus (NIDDM) characterised bylan early age of onset (< 25 years) and an autosomal dominant mode of inheritance. |
| 187 | 9243109 | MODY is genetically heterogeneous with three different genes identified to date; hepatocyte nuclear factor 4 alpha (HNF-4 alpha) [MODY1], glucokinase [MODY2] and hepatocyte nuclear factor 1 alpha (HNF-1 alpha) [MODY3]. |
| 188 | 9267996 | To address the question of whether genetic variability of HNF-4alpha is associated with late onset non-insulin-dependent diabetes mellitus (NIDDM) we have sequenced the coding region and intron/exon boundaries of the gene in 36 randomly recruited Danish NIDDM patients. |
| 189 | 9294105 | Mutations in the hepatocyte nuclear factor(HNF)-4alpha/MODY1, glucokinase/MODY2, and HNF-1alpha/MODY3 genes can cause this form of diabetes. |
| 190 | 9294105 | In contrast to the glucokinase and HNF-1alpha genes, mutations in the HNF-4alpha gene are a relatively uncommon cause of MODY, and our understanding of the MODY1 form of diabetes is based on studies of only a single family, the R-W pedigree. |
| 191 | 9294105 | Mutations in the hepatocyte nuclear factor(HNF)-4alpha/MODY1, glucokinase/MODY2, and HNF-1alpha/MODY3 genes can cause this form of diabetes. |
| 192 | 9294105 | In contrast to the glucokinase and HNF-1alpha genes, mutations in the HNF-4alpha gene are a relatively uncommon cause of MODY, and our understanding of the MODY1 form of diabetes is based on studies of only a single family, the R-W pedigree. |
| 193 | 9313765 | The results suggest that mutations in the HNF-4 alpha gene may cause early-onset NIDDM/MODY in Japanese but they are less common than mutations in the HNF-1 alpha/MODY3 gene. |
| 194 | 9356021 | Diminished insulin and glucagon secretory responses to arginine in nondiabetic subjects with a mutation in the hepatocyte nuclear factor-4alpha/MODY1 gene. |
| 195 | 9356021 | Nondiabetic subjects with the Q268X mutation in the hepatocyte nuclear factor (HNF)-4alpha/MODY1 gene have impaired glucose-induced insulin secretion. |
| 196 | 9356021 | The decreased ISR to arginine in the ND[+] group compared with the ND[-] group, magnified by glucose potentiation, indicated that HNF-4alpha affects the signaling pathway for arginine-induced insulin secretion. |
| 197 | 9356021 | Diminished insulin and glucagon secretory responses to arginine in nondiabetic subjects with a mutation in the hepatocyte nuclear factor-4alpha/MODY1 gene. |
| 198 | 9356021 | Nondiabetic subjects with the Q268X mutation in the hepatocyte nuclear factor (HNF)-4alpha/MODY1 gene have impaired glucose-induced insulin secretion. |
| 199 | 9356021 | The decreased ISR to arginine in the ND[+] group compared with the ND[-] group, magnified by glucose potentiation, indicated that HNF-4alpha affects the signaling pathway for arginine-induced insulin secretion. |
| 200 | 9356021 | Diminished insulin and glucagon secretory responses to arginine in nondiabetic subjects with a mutation in the hepatocyte nuclear factor-4alpha/MODY1 gene. |
| 201 | 9356021 | Nondiabetic subjects with the Q268X mutation in the hepatocyte nuclear factor (HNF)-4alpha/MODY1 gene have impaired glucose-induced insulin secretion. |
| 202 | 9356021 | The decreased ISR to arginine in the ND[+] group compared with the ND[-] group, magnified by glucose potentiation, indicated that HNF-4alpha affects the signaling pathway for arginine-induced insulin secretion. |
| 203 | 9364344 | The pathophysiology of the MODY subtypes is variable with both increased and decreased insulin levels being seen. |
| 204 | 9371825 | A nonsense mutation (Q268X) in exon 7 of the HNF4alpha gene is responsible for an autosomal dominant, early-onset form of non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young; gene named MODY1). |
| 205 | 9371825 | By exploiting this system we have identified several genes encoding components of the glucose-dependent insulin secretion pathway whose expression is dependent upon HNF4alpha. |
| 206 | 9371825 | These include glucose transporter 2, and the glycolytic enzymes aldolase B and glyceraldehyde-3-phosphate dehydrogenase, and liver pyruvate kinase. |
| 207 | 9371825 | A nonsense mutation (Q268X) in exon 7 of the HNF4alpha gene is responsible for an autosomal dominant, early-onset form of non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young; gene named MODY1). |
| 208 | 9371825 | By exploiting this system we have identified several genes encoding components of the glucose-dependent insulin secretion pathway whose expression is dependent upon HNF4alpha. |
| 209 | 9371825 | These include glucose transporter 2, and the glycolytic enzymes aldolase B and glyceraldehyde-3-phosphate dehydrogenase, and liver pyruvate kinase. |
| 210 | 9375718 | Analysis of the glucokinase gene in Mexican families displaying early-onset non-insulin-dependent diabetes mellitus including MODY families. |
| 211 | 9375718 | In Caucasian population, mutations in the glucokinase gene, the TCF1, and TCF14 genes, have been identified in a subgroup of early-onset NIDDM patients denominated MODY (maturity-onset diabetes of the young), which show an autosomal dominant pattern of inheritance. |
| 212 | 9375718 | As a first step in the molecular characterization of Mexican families displaying early-onset NIDDM we searched for mutations in the glucokinase gene through SSCP analysis and/or direct sequencing in 26 individuals from 22 independent families, where at least four can be classified as MODY. |
| 213 | 9375718 | The phenotype and clinical profile of some of the studied patients is compatible with that of patients carrying mutations in the TCF1 or TCF14 genes, while others may carry mutations in different loci. |
| 214 | 9375718 | Analysis of the glucokinase gene in Mexican families displaying early-onset non-insulin-dependent diabetes mellitus including MODY families. |
| 215 | 9375718 | In Caucasian population, mutations in the glucokinase gene, the TCF1, and TCF14 genes, have been identified in a subgroup of early-onset NIDDM patients denominated MODY (maturity-onset diabetes of the young), which show an autosomal dominant pattern of inheritance. |
| 216 | 9375718 | As a first step in the molecular characterization of Mexican families displaying early-onset NIDDM we searched for mutations in the glucokinase gene through SSCP analysis and/or direct sequencing in 26 individuals from 22 independent families, where at least four can be classified as MODY. |
| 217 | 9375718 | The phenotype and clinical profile of some of the studied patients is compatible with that of patients carrying mutations in the TCF1 or TCF14 genes, while others may carry mutations in different loci. |
| 218 | 9375718 | Analysis of the glucokinase gene in Mexican families displaying early-onset non-insulin-dependent diabetes mellitus including MODY families. |
| 219 | 9375718 | In Caucasian population, mutations in the glucokinase gene, the TCF1, and TCF14 genes, have been identified in a subgroup of early-onset NIDDM patients denominated MODY (maturity-onset diabetes of the young), which show an autosomal dominant pattern of inheritance. |
| 220 | 9375718 | As a first step in the molecular characterization of Mexican families displaying early-onset NIDDM we searched for mutations in the glucokinase gene through SSCP analysis and/or direct sequencing in 26 individuals from 22 independent families, where at least four can be classified as MODY. |
| 221 | 9375718 | The phenotype and clinical profile of some of the studied patients is compatible with that of patients carrying mutations in the TCF1 or TCF14 genes, while others may carry mutations in different loci. |
| 222 | 9375718 | Analysis of the glucokinase gene in Mexican families displaying early-onset non-insulin-dependent diabetes mellitus including MODY families. |
| 223 | 9375718 | In Caucasian population, mutations in the glucokinase gene, the TCF1, and TCF14 genes, have been identified in a subgroup of early-onset NIDDM patients denominated MODY (maturity-onset diabetes of the young), which show an autosomal dominant pattern of inheritance. |
| 224 | 9375718 | As a first step in the molecular characterization of Mexican families displaying early-onset NIDDM we searched for mutations in the glucokinase gene through SSCP analysis and/or direct sequencing in 26 individuals from 22 independent families, where at least four can be classified as MODY. |
| 225 | 9375718 | The phenotype and clinical profile of some of the studied patients is compatible with that of patients carrying mutations in the TCF1 or TCF14 genes, while others may carry mutations in different loci. |
| 226 | 9449683 | A missense mutation in hepatocyte nuclear factor-4 alpha, resulting in a reduced transactivation activity, in human late-onset non-insulin-dependent diabetes mellitus. |
| 227 | 9449683 | Recent studies have found mutations in the hepatocyte nuclear factor-4 alpha gene (HNF-4alpha) in families with maturity-onset diabetes of the young (MODY), an autosomal dominant form of diabetes characterized by early age at onset and a defect in glucose-stimulated insulin secretion. |
| 228 | 9449683 | A missense mutation in hepatocyte nuclear factor-4 alpha, resulting in a reduced transactivation activity, in human late-onset non-insulin-dependent diabetes mellitus. |
| 229 | 9449683 | Recent studies have found mutations in the hepatocyte nuclear factor-4 alpha gene (HNF-4alpha) in families with maturity-onset diabetes of the young (MODY), an autosomal dominant form of diabetes characterized by early age at onset and a defect in glucose-stimulated insulin secretion. |
| 230 | 9460079 | Notably, three MODY genes encode transcription factors implicated in the regulation of insulin gene transcription: hepatocyte nuclear factors 1 alpha and 4 alpha, and islet duodenum homeobox-1 (IDX-1, also known as IPF-1). |
| 231 | 9460079 | Recently, mouse knockouts of the transcription factors Pax4, Pax6, beta 2/neuroD, and Isl-1 result in severe anomalies in the development of the endocrine pancreas. |
| 232 | 9472859 | Maturity-onset diabetes of the young (MODY) can be defined by the clinical characteristics of early-onset Type 2 (non-insulin-dependent) diabetes and autosomal dominant inheritance. |
| 233 | 9472859 | Mutations in four genes have been shown to cause MODY: glucokinase, hepatic nuclear factor 1 alpha (HNF1alpha), hepatic nuclear factor 4 alpha (HNF4alpha) and insulin promoter [corrected] factor 1 (IPF1). |
| 234 | 9472859 | Patients with HNF4alpha and IPF1 mutations show a similar clinical picture to HNF1alpha although diabetes may be diagnosed later. |
| 235 | 9472859 | Maturity-onset diabetes of the young (MODY) can be defined by the clinical characteristics of early-onset Type 2 (non-insulin-dependent) diabetes and autosomal dominant inheritance. |
| 236 | 9472859 | Mutations in four genes have been shown to cause MODY: glucokinase, hepatic nuclear factor 1 alpha (HNF1alpha), hepatic nuclear factor 4 alpha (HNF4alpha) and insulin promoter [corrected] factor 1 (IPF1). |
| 237 | 9472859 | Patients with HNF4alpha and IPF1 mutations show a similar clinical picture to HNF1alpha although diabetes may be diagnosed later. |
| 238 | 9472859 | Maturity-onset diabetes of the young (MODY) can be defined by the clinical characteristics of early-onset Type 2 (non-insulin-dependent) diabetes and autosomal dominant inheritance. |
| 239 | 9472859 | Mutations in four genes have been shown to cause MODY: glucokinase, hepatic nuclear factor 1 alpha (HNF1alpha), hepatic nuclear factor 4 alpha (HNF4alpha) and insulin promoter [corrected] factor 1 (IPF1). |
| 240 | 9472859 | Patients with HNF4alpha and IPF1 mutations show a similar clinical picture to HNF1alpha although diabetes may be diagnosed later. |
| 241 | 9522422 | A search for mutations of the glucokinase and HNF-1 alpha genes and for mitochondrial DNA was made, anti-islet and anti-GAD antibodies were determined and HLA class II genotyping was performed. |
| 242 | 9522422 | MODY is a form of diabetes which has an autosomal dominant inheritance for which 3 genes have already been implicated (MODY1, HNF-4 gene; MODY2, glucokinase gene, and MODY3, HNF-1 alpha gene). |
| 243 | 9531829 | Maturity-onset diabetes of the young (MODY) is a clinically and genetically heterogenous disorder characterized by autosomal dominant inheritance with onset usually before 25 years of age, and a primary defect in glucose-stimulated insulin secretion. |
| 244 | 9531829 | These are the genes encoding the glycolytic enzyme glucokinase, three liver-enriched transcription factors, hepatocyte nuclear factor (HNF)-1 alpha, HNF-1 beta and HNF-4 alpha, and the gene encoding the transcription factor, insulin promoter factor-1 (IPF-1). |
| 245 | 9531829 | Maturity-onset diabetes of the young (MODY) is a clinically and genetically heterogenous disorder characterized by autosomal dominant inheritance with onset usually before 25 years of age, and a primary defect in glucose-stimulated insulin secretion. |
| 246 | 9531829 | These are the genes encoding the glycolytic enzyme glucokinase, three liver-enriched transcription factors, hepatocyte nuclear factor (HNF)-1 alpha, HNF-1 beta and HNF-4 alpha, and the gene encoding the transcription factor, insulin promoter factor-1 (IPF-1). |
| 247 | 9539292 | To date, three MODY genes have been identified on chromosomes 20q (MODY1/hepatic nuclear factor (HNF)-4alpha), 7p (MODY2/glucokinase) and 12q (MODY3/HNF-1alpha). |
| 248 | 9539292 | In contrast, MODY1 and MODY3 are characterised by severe insulin secretory defects, and by major hyperglycaemia associated with microvascular complications. |
| 249 | 9539292 | To date, three MODY genes have been identified on chromosomes 20q (MODY1/hepatic nuclear factor (HNF)-4alpha), 7p (MODY2/glucokinase) and 12q (MODY3/HNF-1alpha). |
| 250 | 9539292 | In contrast, MODY1 and MODY3 are characterised by severe insulin secretory defects, and by major hyperglycaemia associated with microvascular complications. |
| 251 | 9562352 | Thirty-four percent of the MODY patients had mild and 13% had severe non-proliferative or proliferative retinopathy; this figure did not differ from the figures in insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) patients matched for duration and glycaemic control but not for age. |
| 252 | 9562352 | Neither did the prevalence of microalbuminuria differ between MODY3 and IDDM or NIDDM patients (19 vs 24 and 23%). |
| 253 | 9562352 | Hypertension was less frequent in MODY3 and IDDM than in NIDDM (24.5 and 19 vs 53.7%; p < 0.001). |
| 254 | 9593777 | Mutations in the gene for the transcription factor hepatocyte nuclear factor (HNF) 1alpha cause maturity-onset diabetes of the young (MODY) 3, a form of diabetes that results from defects in insulin secretion. |
| 255 | 9593777 | Since the nature of these defects has not been defined, we compared insulin secretory function in heterozygous [HNF-1alpha (+/-)] or homozygous [HNF-1alpha (-/-)] mice with null mutations in the HNF-1alpha gene with their wild-type littermates [HNF-1alpha (+/+)]. |
| 256 | 9593777 | Insulin secretory responses to glucose and arginine in the perfused pancreas and perifused islets from HNF-1alpha (-/-) mice were < 15% of the values in the other two groups and were associated with similar reductions in intracellular Ca2+ responses. |
| 257 | 9593777 | These defects were not due to a decrease in glucokinase or insulin gene transcription. beta cell mass adjusted for body weight was not reduced in the (-/-) animals, although pancreatic insulin content adjusted for pancreas weight was slightly lower (0.06+/-0.01 vs. 0.10+/-0.01 microg/mg, P < 0.01) than in the (+/+) animals. |
| 258 | 9626139 | Mutations of the hepatocyte nuclear factor-1 alpha (HNF1 alpha) gene are an important cause of autosomal dominant diabetes with onset before age 25 yr [maturity-onset diabetes of the young (MODY)], and some regions of the HNF1 alpha gene appear to be hot spots for mutations. |
| 259 | 9685261 | Mutations in HNF-1alphaand HNF-4alpha genes impair insulin secretion and cause type 2 diabetes. |
| 260 | 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. |
| 261 | 9685261 | HNF-3beta positively regulated the expression of HNF-4alpha/HNF-1alpha and their downstream targets, implicating a role in diabetes. |
| 262 | 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. |
| 263 | 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. |
| 264 | 9685261 | Mutations in HNF-1alphaand HNF-4alpha genes impair insulin secretion and cause type 2 diabetes. |
| 265 | 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. |
| 266 | 9685261 | HNF-3beta positively regulated the expression of HNF-4alpha/HNF-1alpha and their downstream targets, implicating a role in diabetes. |
| 267 | 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. |
| 268 | 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. |
| 269 | 9685261 | Mutations in HNF-1alphaand HNF-4alpha genes impair insulin secretion and cause type 2 diabetes. |
| 270 | 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. |
| 271 | 9685261 | HNF-3beta positively regulated the expression of HNF-4alpha/HNF-1alpha and their downstream targets, implicating a role in diabetes. |
| 272 | 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. |
| 273 | 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. |
| 274 | 9685261 | Mutations in HNF-1alphaand HNF-4alpha genes impair insulin secretion and cause type 2 diabetes. |
| 275 | 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. |
| 276 | 9685261 | HNF-3beta positively regulated the expression of HNF-4alpha/HNF-1alpha and their downstream targets, implicating a role in diabetes. |
| 277 | 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. |
| 278 | 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. |
| 279 | 9703322 | Because the dimerization domain is intact in many of the mutant forms of HNF-1alpha found in MODY subjects, these mutant proteins may impair pancreatic beta-cell function by forming nonproductive dimers with wild-type protein, thereby inhibiting its activity; that is, they are dominant-negative mutations. |
| 280 | 9715376 | The fact that both insulin resistance and impaired insulin release have been found to precede and predict NIDDM in prospective studies may be in part a reflection of just such relatedness. 4) Direct genetic analysis is effective in rarer forms of glucose intolerance (MODY, mitochondrial mutations, etc.) but encounters serious difficulties with typical late-onset NIDDM. |
| 281 | 9715376 | Incidentally, any defect in insulin secretion, whether in normoglycemic or hyperglycemic persons, could be due to other factors than primary beta-cell dysfunction: amyloid deposits in the pancreas (126), changes in insulin secretagogues (amylin, GLP-1, GIP, galanin) (127-130), early intrauterine malnutrition (131). |
| 282 | 9726235 | Mutations of the hepatocyte nuclear factor (HNF)-1alpha gene cause impaired insulin secretion and hyperglycemia in patients with maturity-onset diabetes of the young (MODY)3. |
| 283 | 9736233 | Maturity-onset diabetes of the young (MODY) is a form of diabetes mellitus characterized by autosomal dominant inheritance, onset usually before 25 y of age and a primary defect in glucose-stimulated insulin secretion. |
| 284 | 9736233 | Mutations in the genes encoding the glycolytic enzyme glucokinase, the liver-enriched transcription factors, hepatocyte nuclear factor-1alpha (HNF-1alpha), HNF-1beta and HNF-4alpha, and the transcription factor, insulin promoter factor-1 (IPF-1) have all been associated with MODY. |
| 285 | 9736233 | The results presented here indicate that the glucokinase form of MODY occurs in Norway. |
| 286 | 9736233 | Maturity-onset diabetes of the young (MODY) is a form of diabetes mellitus characterized by autosomal dominant inheritance, onset usually before 25 y of age and a primary defect in glucose-stimulated insulin secretion. |
| 287 | 9736233 | Mutations in the genes encoding the glycolytic enzyme glucokinase, the liver-enriched transcription factors, hepatocyte nuclear factor-1alpha (HNF-1alpha), HNF-1beta and HNF-4alpha, and the transcription factor, insulin promoter factor-1 (IPF-1) have all been associated with MODY. |
| 288 | 9736233 | The results presented here indicate that the glucokinase form of MODY occurs in Norway. |
| 289 | 9736233 | Maturity-onset diabetes of the young (MODY) is a form of diabetes mellitus characterized by autosomal dominant inheritance, onset usually before 25 y of age and a primary defect in glucose-stimulated insulin secretion. |
| 290 | 9736233 | Mutations in the genes encoding the glycolytic enzyme glucokinase, the liver-enriched transcription factors, hepatocyte nuclear factor-1alpha (HNF-1alpha), HNF-1beta and HNF-4alpha, and the transcription factor, insulin promoter factor-1 (IPF-1) have all been associated with MODY. |
| 291 | 9736233 | The results presented here indicate that the glucokinase form of MODY occurs in Norway. |
| 292 | 9754819 | Maturity-onset diabetes of the young (MODY) is a heterogeneous subtype of non-insulin-dependent diabetes mellitus characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. |
| 293 | 9754819 | To date five MODY genes have been identified: hepatocyte nuclear factor-4 alpha (HNF-4alpha/MODY1/TCF14) on chromosome 20q, glucokinase (GCK/MODY2) on chromosome 7p, hepatocyte nuclear factor-1 alpha (HNF-1alpha/MODY3/TCF1) on chromosome 12q, insulin promoter factor-1 (IPF1/MODY4) on chromosome 13q and hepatocyte nuclear factor-1 beta (HNF-1beta/MODY5/TCF2) on chromosome 17cen-q. |
| 294 | 9754819 | We have screened the HNF-4alpha, HNF-1alpha and HNF-1beta genes in members of 18 MODY kindreds who tested negative for glucokinase mutations. |
| 295 | 9754819 | Five missense (G31D, R159W, A161T, R200W, R271W), one substitution at the splice donor site of intron 5 (IVS5nt + 2T-->A) and one deletion mutation (P379fsdelT) were found in the HNF-1alpha gene, but no MODY-associated mutations were found in the HNF-4alpha and HNF-1beta genes. |
| 296 | 9754819 | Of 67 French MODY families that we have now studied, 42 (63%) have mutations in the glucokinase gene, 14 (21%) have mutations in the HNF-1alpha gene, and 11 (16%) have no mutations in the HNF-4alpha, IPF1 and HNF-1beta genes. |
| 297 | 9754819 | Maturity-onset diabetes of the young (MODY) is a heterogeneous subtype of non-insulin-dependent diabetes mellitus characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. |
| 298 | 9754819 | To date five MODY genes have been identified: hepatocyte nuclear factor-4 alpha (HNF-4alpha/MODY1/TCF14) on chromosome 20q, glucokinase (GCK/MODY2) on chromosome 7p, hepatocyte nuclear factor-1 alpha (HNF-1alpha/MODY3/TCF1) on chromosome 12q, insulin promoter factor-1 (IPF1/MODY4) on chromosome 13q and hepatocyte nuclear factor-1 beta (HNF-1beta/MODY5/TCF2) on chromosome 17cen-q. |
| 299 | 9754819 | We have screened the HNF-4alpha, HNF-1alpha and HNF-1beta genes in members of 18 MODY kindreds who tested negative for glucokinase mutations. |
| 300 | 9754819 | Five missense (G31D, R159W, A161T, R200W, R271W), one substitution at the splice donor site of intron 5 (IVS5nt + 2T-->A) and one deletion mutation (P379fsdelT) were found in the HNF-1alpha gene, but no MODY-associated mutations were found in the HNF-4alpha and HNF-1beta genes. |
| 301 | 9754819 | Of 67 French MODY families that we have now studied, 42 (63%) have mutations in the glucokinase gene, 14 (21%) have mutations in the HNF-1alpha gene, and 11 (16%) have no mutations in the HNF-4alpha, IPF1 and HNF-1beta genes. |
| 302 | 9754819 | Maturity-onset diabetes of the young (MODY) is a heterogeneous subtype of non-insulin-dependent diabetes mellitus characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. |
| 303 | 9754819 | To date five MODY genes have been identified: hepatocyte nuclear factor-4 alpha (HNF-4alpha/MODY1/TCF14) on chromosome 20q, glucokinase (GCK/MODY2) on chromosome 7p, hepatocyte nuclear factor-1 alpha (HNF-1alpha/MODY3/TCF1) on chromosome 12q, insulin promoter factor-1 (IPF1/MODY4) on chromosome 13q and hepatocyte nuclear factor-1 beta (HNF-1beta/MODY5/TCF2) on chromosome 17cen-q. |
| 304 | 9754819 | We have screened the HNF-4alpha, HNF-1alpha and HNF-1beta genes in members of 18 MODY kindreds who tested negative for glucokinase mutations. |
| 305 | 9754819 | Five missense (G31D, R159W, A161T, R200W, R271W), one substitution at the splice donor site of intron 5 (IVS5nt + 2T-->A) and one deletion mutation (P379fsdelT) were found in the HNF-1alpha gene, but no MODY-associated mutations were found in the HNF-4alpha and HNF-1beta genes. |
| 306 | 9754819 | Of 67 French MODY families that we have now studied, 42 (63%) have mutations in the glucokinase gene, 14 (21%) have mutations in the HNF-1alpha gene, and 11 (16%) have no mutations in the HNF-4alpha, IPF1 and HNF-1beta genes. |
| 307 | 9754819 | Maturity-onset diabetes of the young (MODY) is a heterogeneous subtype of non-insulin-dependent diabetes mellitus characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. |
| 308 | 9754819 | To date five MODY genes have been identified: hepatocyte nuclear factor-4 alpha (HNF-4alpha/MODY1/TCF14) on chromosome 20q, glucokinase (GCK/MODY2) on chromosome 7p, hepatocyte nuclear factor-1 alpha (HNF-1alpha/MODY3/TCF1) on chromosome 12q, insulin promoter factor-1 (IPF1/MODY4) on chromosome 13q and hepatocyte nuclear factor-1 beta (HNF-1beta/MODY5/TCF2) on chromosome 17cen-q. |
| 309 | 9754819 | We have screened the HNF-4alpha, HNF-1alpha and HNF-1beta genes in members of 18 MODY kindreds who tested negative for glucokinase mutations. |
| 310 | 9754819 | Five missense (G31D, R159W, A161T, R200W, R271W), one substitution at the splice donor site of intron 5 (IVS5nt + 2T-->A) and one deletion mutation (P379fsdelT) were found in the HNF-1alpha gene, but no MODY-associated mutations were found in the HNF-4alpha and HNF-1beta genes. |
| 311 | 9754819 | Of 67 French MODY families that we have now studied, 42 (63%) have mutations in the glucokinase gene, 14 (21%) have mutations in the HNF-1alpha gene, and 11 (16%) have no mutations in the HNF-4alpha, IPF1 and HNF-1beta genes. |
| 312 | 9754819 | Maturity-onset diabetes of the young (MODY) is a heterogeneous subtype of non-insulin-dependent diabetes mellitus characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. |
| 313 | 9754819 | To date five MODY genes have been identified: hepatocyte nuclear factor-4 alpha (HNF-4alpha/MODY1/TCF14) on chromosome 20q, glucokinase (GCK/MODY2) on chromosome 7p, hepatocyte nuclear factor-1 alpha (HNF-1alpha/MODY3/TCF1) on chromosome 12q, insulin promoter factor-1 (IPF1/MODY4) on chromosome 13q and hepatocyte nuclear factor-1 beta (HNF-1beta/MODY5/TCF2) on chromosome 17cen-q. |
| 314 | 9754819 | We have screened the HNF-4alpha, HNF-1alpha and HNF-1beta genes in members of 18 MODY kindreds who tested negative for glucokinase mutations. |
| 315 | 9754819 | Five missense (G31D, R159W, A161T, R200W, R271W), one substitution at the splice donor site of intron 5 (IVS5nt + 2T-->A) and one deletion mutation (P379fsdelT) were found in the HNF-1alpha gene, but no MODY-associated mutations were found in the HNF-4alpha and HNF-1beta genes. |
| 316 | 9754819 | Of 67 French MODY families that we have now studied, 42 (63%) have mutations in the glucokinase gene, 14 (21%) have mutations in the HNF-1alpha gene, and 11 (16%) have no mutations in the HNF-4alpha, IPF1 and HNF-1beta genes. |
| 317 | 9780731 | Maturity-onset diabetes of the young (MODY) is a monogenic form of non-insulin-dependent diabetes mellitus (NIDDM) characterized by an early age of onset, often in childhood or adolescence and usually < 25 years of age, and autosomal dominant inheritance. |
| 318 | 9780731 | Clinical characterization of patients with MODY indicates that impaired insulin secretion is the primary defect responsible for the hyperglycemia in these patients. |
| 319 | 9780731 | Genetic studies have thus far identified five MODY susceptibility genes, four of which encode transcription factors; HNF (hepatocyte nuclear factor)-1 alpha, HNF-1 beta, HNF-4 alpha, and IPF1. |
| 320 | 9780731 | Maturity-onset diabetes of the young (MODY) is a monogenic form of non-insulin-dependent diabetes mellitus (NIDDM) characterized by an early age of onset, often in childhood or adolescence and usually < 25 years of age, and autosomal dominant inheritance. |
| 321 | 9780731 | Clinical characterization of patients with MODY indicates that impaired insulin secretion is the primary defect responsible for the hyperglycemia in these patients. |
| 322 | 9780731 | Genetic studies have thus far identified five MODY susceptibility genes, four of which encode transcription factors; HNF (hepatocyte nuclear factor)-1 alpha, HNF-1 beta, HNF-4 alpha, and IPF1. |
| 323 | 9780731 | Maturity-onset diabetes of the young (MODY) is a monogenic form of non-insulin-dependent diabetes mellitus (NIDDM) characterized by an early age of onset, often in childhood or adolescence and usually < 25 years of age, and autosomal dominant inheritance. |
| 324 | 9780731 | Clinical characterization of patients with MODY indicates that impaired insulin secretion is the primary defect responsible for the hyperglycemia in these patients. |
| 325 | 9780731 | Genetic studies have thus far identified five MODY susceptibility genes, four of which encode transcription factors; HNF (hepatocyte nuclear factor)-1 alpha, HNF-1 beta, HNF-4 alpha, and IPF1. |
| 326 | 9792550 | Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous monogenic form of NIDDM characterized by an early age of onset and autosomal dominant inheritance, and linkage studies have identified genes that are mutated in different MODY pedigrees on chromosome 20 (MODY1 locus, hepatocyte nuclear factor-4alpha [HNF-4alpha] gene), chromosome 7 (MODY2 locus, glucokinase gene), and chromosome 12 (MODY3 locus, HNF-1alpha gene). |
| 327 | 9792714 | Critical structural elements and multitarget protein interactions of the transcriptional activator AF-1 of hepatocyte nuclear factor 4. |
| 328 | 9792714 | Recently, we showed that the 24 N-terminal residues of HNF-4 function as an acidic transcriptional activator, termed AF-1 (Hadzopoulou-Cladaras, M., Kistanova, E., Evagelopoulou, C., Zeng, S. , Cladaras C., and Ladias, J. |
| 329 | 9792714 | We showed that the aromatic and bulky hydrophobic residues Tyr6, Tyr14, Phe19, Lys10, and Lys17 are essential for AF-1 function. |
| 330 | 9792714 | Positional changes of Tyr6 and Tyr14 reduced AF-1 activity, underscoring the importance of primary structure for this activator. |
| 331 | 9792714 | Our analysis also indicated that AF-1 is bipartite, consisting of two modules that synergize to activate transcription. |
| 332 | 9792714 | More important, AF-1 shares common structural motifs and molecular targets with the activators of the tumor suppressor protein p53 and NF-kappaB-p65, suggesting similar mechanisms of action. |
| 333 | 9792714 | Remarkably, AF-1 interacted specifically with multiple transcriptional targets, including the TATA-binding protein; the TATA-binding protein-associated factors TAFII31 and TAFII80; transcription factor IIB; transcription factor IIH-p62; and the coactivators cAMP-responsive element-binding protein-binding protein, ADA2, and PC4. |
| 334 | 9792714 | The interaction of AF-1 with proteins that regulate distinct steps of transcription may provide a mechanism for synergistic activation of gene expression by AF-1. |
| 335 | 9792714 | Critical structural elements and multitarget protein interactions of the transcriptional activator AF-1 of hepatocyte nuclear factor 4. |
| 336 | 9792714 | Recently, we showed that the 24 N-terminal residues of HNF-4 function as an acidic transcriptional activator, termed AF-1 (Hadzopoulou-Cladaras, M., Kistanova, E., Evagelopoulou, C., Zeng, S. , Cladaras C., and Ladias, J. |
| 337 | 9792714 | We showed that the aromatic and bulky hydrophobic residues Tyr6, Tyr14, Phe19, Lys10, and Lys17 are essential for AF-1 function. |
| 338 | 9792714 | Positional changes of Tyr6 and Tyr14 reduced AF-1 activity, underscoring the importance of primary structure for this activator. |
| 339 | 9792714 | Our analysis also indicated that AF-1 is bipartite, consisting of two modules that synergize to activate transcription. |
| 340 | 9792714 | More important, AF-1 shares common structural motifs and molecular targets with the activators of the tumor suppressor protein p53 and NF-kappaB-p65, suggesting similar mechanisms of action. |
| 341 | 9792714 | Remarkably, AF-1 interacted specifically with multiple transcriptional targets, including the TATA-binding protein; the TATA-binding protein-associated factors TAFII31 and TAFII80; transcription factor IIB; transcription factor IIH-p62; and the coactivators cAMP-responsive element-binding protein-binding protein, ADA2, and PC4. |
| 342 | 9792714 | The interaction of AF-1 with proteins that regulate distinct steps of transcription may provide a mechanism for synergistic activation of gene expression by AF-1. |
| 343 | 9812974 | SRC-1 and GRIP1 coactivate transcription with hepatocyte nuclear factor 4. |
| 344 | 9812974 | In this study, we show that SRC-1 and GRIP1, which act as coactivators for various nuclear receptors, associate with HNF4 in vivo and enhance its transactivation potential. |
| 345 | 9812974 | The AF-2 domain of HNF4 is required for this interaction and for the potentiation of transcriptional activity by these coactivators. p300 can also serve as a coactivator with HNF4, and it synergizes with SRC-1 to further augment the activity of HNF4. |
| 346 | 9812974 | HNF4 is also a key regulator of the expression of hepatocyte nuclear factor-1 (HNF1). |
| 347 | 9812974 | The overexpression of SRC-1 or GRIP1 enhances expression from a HNF1 gene promoter-reporter in HepG2 hepatoma cells, and this requires an intact HNF4-binding site in the HNF1 gene promoter. |
| 348 | 9812974 | Type 1 maturity onset diabetes of young (MODY), which is characterized by abnormal glucose-mediated insulin secretion, is caused by mutations of the HNF4 gene. |
| 349 | 9812974 | A mutation of the HNF4-binding site in the HNF1 gene promoter has also been associated with MODY. |
| 350 | 9812974 | Thus, HNF4 is involved in the regulation of glucose homeostasis at several levels and along with the SRC-1, GRIP1, and p300 may play an important role in the pathophysiology of non-insulin-dependent diabetes mellitus. |
| 351 | 9812974 | SRC-1 and GRIP1 coactivate transcription with hepatocyte nuclear factor 4. |
| 352 | 9812974 | In this study, we show that SRC-1 and GRIP1, which act as coactivators for various nuclear receptors, associate with HNF4 in vivo and enhance its transactivation potential. |
| 353 | 9812974 | The AF-2 domain of HNF4 is required for this interaction and for the potentiation of transcriptional activity by these coactivators. p300 can also serve as a coactivator with HNF4, and it synergizes with SRC-1 to further augment the activity of HNF4. |
| 354 | 9812974 | HNF4 is also a key regulator of the expression of hepatocyte nuclear factor-1 (HNF1). |
| 355 | 9812974 | The overexpression of SRC-1 or GRIP1 enhances expression from a HNF1 gene promoter-reporter in HepG2 hepatoma cells, and this requires an intact HNF4-binding site in the HNF1 gene promoter. |
| 356 | 9812974 | Type 1 maturity onset diabetes of young (MODY), which is characterized by abnormal glucose-mediated insulin secretion, is caused by mutations of the HNF4 gene. |
| 357 | 9812974 | A mutation of the HNF4-binding site in the HNF1 gene promoter has also been associated with MODY. |
| 358 | 9812974 | Thus, HNF4 is involved in the regulation of glucose homeostasis at several levels and along with the SRC-1, GRIP1, and p300 may play an important role in the pathophysiology of non-insulin-dependent diabetes mellitus. |
| 359 | 9812974 | SRC-1 and GRIP1 coactivate transcription with hepatocyte nuclear factor 4. |
| 360 | 9812974 | In this study, we show that SRC-1 and GRIP1, which act as coactivators for various nuclear receptors, associate with HNF4 in vivo and enhance its transactivation potential. |
| 361 | 9812974 | The AF-2 domain of HNF4 is required for this interaction and for the potentiation of transcriptional activity by these coactivators. p300 can also serve as a coactivator with HNF4, and it synergizes with SRC-1 to further augment the activity of HNF4. |
| 362 | 9812974 | HNF4 is also a key regulator of the expression of hepatocyte nuclear factor-1 (HNF1). |
| 363 | 9812974 | The overexpression of SRC-1 or GRIP1 enhances expression from a HNF1 gene promoter-reporter in HepG2 hepatoma cells, and this requires an intact HNF4-binding site in the HNF1 gene promoter. |
| 364 | 9812974 | Type 1 maturity onset diabetes of young (MODY), which is characterized by abnormal glucose-mediated insulin secretion, is caused by mutations of the HNF4 gene. |
| 365 | 9812974 | A mutation of the HNF4-binding site in the HNF1 gene promoter has also been associated with MODY. |
| 366 | 9812974 | Thus, HNF4 is involved in the regulation of glucose homeostasis at several levels and along with the SRC-1, GRIP1, and p300 may play an important role in the pathophysiology of non-insulin-dependent diabetes mellitus. |
| 367 | 9812974 | SRC-1 and GRIP1 coactivate transcription with hepatocyte nuclear factor 4. |
| 368 | 9812974 | In this study, we show that SRC-1 and GRIP1, which act as coactivators for various nuclear receptors, associate with HNF4 in vivo and enhance its transactivation potential. |
| 369 | 9812974 | The AF-2 domain of HNF4 is required for this interaction and for the potentiation of transcriptional activity by these coactivators. p300 can also serve as a coactivator with HNF4, and it synergizes with SRC-1 to further augment the activity of HNF4. |
| 370 | 9812974 | HNF4 is also a key regulator of the expression of hepatocyte nuclear factor-1 (HNF1). |
| 371 | 9812974 | The overexpression of SRC-1 or GRIP1 enhances expression from a HNF1 gene promoter-reporter in HepG2 hepatoma cells, and this requires an intact HNF4-binding site in the HNF1 gene promoter. |
| 372 | 9812974 | Type 1 maturity onset diabetes of young (MODY), which is characterized by abnormal glucose-mediated insulin secretion, is caused by mutations of the HNF4 gene. |
| 373 | 9812974 | A mutation of the HNF4-binding site in the HNF1 gene promoter has also been associated with MODY. |
| 374 | 9812974 | Thus, HNF4 is involved in the regulation of glucose homeostasis at several levels and along with the SRC-1, GRIP1, and p300 may play an important role in the pathophysiology of non-insulin-dependent diabetes mellitus. |
| 375 | 9812974 | SRC-1 and GRIP1 coactivate transcription with hepatocyte nuclear factor 4. |
| 376 | 9812974 | In this study, we show that SRC-1 and GRIP1, which act as coactivators for various nuclear receptors, associate with HNF4 in vivo and enhance its transactivation potential. |
| 377 | 9812974 | The AF-2 domain of HNF4 is required for this interaction and for the potentiation of transcriptional activity by these coactivators. p300 can also serve as a coactivator with HNF4, and it synergizes with SRC-1 to further augment the activity of HNF4. |
| 378 | 9812974 | HNF4 is also a key regulator of the expression of hepatocyte nuclear factor-1 (HNF1). |
| 379 | 9812974 | The overexpression of SRC-1 or GRIP1 enhances expression from a HNF1 gene promoter-reporter in HepG2 hepatoma cells, and this requires an intact HNF4-binding site in the HNF1 gene promoter. |
| 380 | 9812974 | Type 1 maturity onset diabetes of young (MODY), which is characterized by abnormal glucose-mediated insulin secretion, is caused by mutations of the HNF4 gene. |
| 381 | 9812974 | A mutation of the HNF4-binding site in the HNF1 gene promoter has also been associated with MODY. |
| 382 | 9812974 | Thus, HNF4 is involved in the regulation of glucose homeostasis at several levels and along with the SRC-1, GRIP1, and p300 may play an important role in the pathophysiology of non-insulin-dependent diabetes mellitus. |
| 383 | 9812974 | SRC-1 and GRIP1 coactivate transcription with hepatocyte nuclear factor 4. |
| 384 | 9812974 | In this study, we show that SRC-1 and GRIP1, which act as coactivators for various nuclear receptors, associate with HNF4 in vivo and enhance its transactivation potential. |
| 385 | 9812974 | The AF-2 domain of HNF4 is required for this interaction and for the potentiation of transcriptional activity by these coactivators. p300 can also serve as a coactivator with HNF4, and it synergizes with SRC-1 to further augment the activity of HNF4. |
| 386 | 9812974 | HNF4 is also a key regulator of the expression of hepatocyte nuclear factor-1 (HNF1). |
| 387 | 9812974 | The overexpression of SRC-1 or GRIP1 enhances expression from a HNF1 gene promoter-reporter in HepG2 hepatoma cells, and this requires an intact HNF4-binding site in the HNF1 gene promoter. |
| 388 | 9812974 | Type 1 maturity onset diabetes of young (MODY), which is characterized by abnormal glucose-mediated insulin secretion, is caused by mutations of the HNF4 gene. |
| 389 | 9812974 | A mutation of the HNF4-binding site in the HNF1 gene promoter has also been associated with MODY. |
| 390 | 9812974 | Thus, HNF4 is involved in the regulation of glucose homeostasis at several levels and along with the SRC-1, GRIP1, and p300 may play an important role in the pathophysiology of non-insulin-dependent diabetes mellitus. |
| 391 | 9812974 | SRC-1 and GRIP1 coactivate transcription with hepatocyte nuclear factor 4. |
| 392 | 9812974 | In this study, we show that SRC-1 and GRIP1, which act as coactivators for various nuclear receptors, associate with HNF4 in vivo and enhance its transactivation potential. |
| 393 | 9812974 | The AF-2 domain of HNF4 is required for this interaction and for the potentiation of transcriptional activity by these coactivators. p300 can also serve as a coactivator with HNF4, and it synergizes with SRC-1 to further augment the activity of HNF4. |
| 394 | 9812974 | HNF4 is also a key regulator of the expression of hepatocyte nuclear factor-1 (HNF1). |
| 395 | 9812974 | The overexpression of SRC-1 or GRIP1 enhances expression from a HNF1 gene promoter-reporter in HepG2 hepatoma cells, and this requires an intact HNF4-binding site in the HNF1 gene promoter. |
| 396 | 9812974 | Type 1 maturity onset diabetes of young (MODY), which is characterized by abnormal glucose-mediated insulin secretion, is caused by mutations of the HNF4 gene. |
| 397 | 9812974 | A mutation of the HNF4-binding site in the HNF1 gene promoter has also been associated with MODY. |
| 398 | 9812974 | Thus, HNF4 is involved in the regulation of glucose homeostasis at several levels and along with the SRC-1, GRIP1, and p300 may play an important role in the pathophysiology of non-insulin-dependent diabetes mellitus. |
| 399 | 9812974 | SRC-1 and GRIP1 coactivate transcription with hepatocyte nuclear factor 4. |
| 400 | 9812974 | In this study, we show that SRC-1 and GRIP1, which act as coactivators for various nuclear receptors, associate with HNF4 in vivo and enhance its transactivation potential. |
| 401 | 9812974 | The AF-2 domain of HNF4 is required for this interaction and for the potentiation of transcriptional activity by these coactivators. p300 can also serve as a coactivator with HNF4, and it synergizes with SRC-1 to further augment the activity of HNF4. |
| 402 | 9812974 | HNF4 is also a key regulator of the expression of hepatocyte nuclear factor-1 (HNF1). |
| 403 | 9812974 | The overexpression of SRC-1 or GRIP1 enhances expression from a HNF1 gene promoter-reporter in HepG2 hepatoma cells, and this requires an intact HNF4-binding site in the HNF1 gene promoter. |
| 404 | 9812974 | Type 1 maturity onset diabetes of young (MODY), which is characterized by abnormal glucose-mediated insulin secretion, is caused by mutations of the HNF4 gene. |
| 405 | 9812974 | A mutation of the HNF4-binding site in the HNF1 gene promoter has also been associated with MODY. |
| 406 | 9812974 | Thus, HNF4 is involved in the regulation of glucose homeostasis at several levels and along with the SRC-1, GRIP1, and p300 may play an important role in the pathophysiology of non-insulin-dependent diabetes mellitus. |
| 407 | 9855864 | The insulin receptor gene on chromosome 19p13 and at least five glucose transporter genes contribute to Type 2 diabetes susceptibility, and further associations may emerge from study of the glycogen synthase gene, the glucokinase gene, the MODY genes, and the leptin gene. |
| 408 | 9867222 | Mutations in the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene are the cause of maturity-onset diabetes of the young type 3 (MODY3), which is characterised by a severe impairment of insulin secretion and an early onset of the disease. |
| 409 | 9867222 | Also at onset of diabetes some MODY patients show similar clinical symptoms and signs as patients with Type I (insulin-dependent) diabetes mellitus. |
| 410 | 9867222 | DR3 or DR4 or both were examined by single-strand conformational polymorphism scanning and direct sequencing of the coding region and the minimal promoter of the HNF-1alpha gene. |
| 411 | 9887471 | Recent studies have shown that mutations in four transcription factors, hepatocyte nuclear factor-4 alpha (HNF-4 alpha), hepatocyte nuclear factor-1 alpha (HNF-1 alpha), hepatocyte nuclear factor-1 beta (HNF-1 beta), and insulin promoter factor-1 (IPF-1), are responsible for maturity onset diabetes of the young (MODY) which is characterised by an early age of onset and autosomal dominant inheritance. |
| 412 | 9887471 | Some mutations in HNF-1 alpha were identified in subjects with atypical forms of insulin-dependent diabetes, and a mutation in HNF-4 alpha and several mutations in IPF-1 were found in type 2 diabetic families with typical late-onset NIDDM. |
| 413 | 9887471 | Recent studies have shown that mutations in four transcription factors, hepatocyte nuclear factor-4 alpha (HNF-4 alpha), hepatocyte nuclear factor-1 alpha (HNF-1 alpha), hepatocyte nuclear factor-1 beta (HNF-1 beta), and insulin promoter factor-1 (IPF-1), are responsible for maturity onset diabetes of the young (MODY) which is characterised by an early age of onset and autosomal dominant inheritance. |
| 414 | 9887471 | Some mutations in HNF-1 alpha were identified in subjects with atypical forms of insulin-dependent diabetes, and a mutation in HNF-4 alpha and several mutations in IPF-1 were found in type 2 diabetic families with typical late-onset NIDDM. |
| 415 | 10199131 | Until now five genes (HNF-4 alpha, glucokinase, HNF-1 alpha, IPF-1 and HNF-1 beta), whose mutation can result in MODY, insulin and insulin receptor genes, and mitochondria DNA have been reported to be responsible for diabetes. |
| 416 | 10322408 | Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of Type 2 diabetes characterized by early onset, autosomal dominant inheritance and primary defects in insulin secretion. |
| 417 | 10322408 | To date, five proteins have been identified whose genetic absence or impairment causes MODY, the enzyme glucokinase (GCK/MODY2) and four transcription factors: hepatocyte nuclear factor 4alpha (HNF-4alpha/MODY1), HNF-1alpha/MODY3, insulin promoter factor 1 (IPF-1/MODY4) and HNF-1beta/MODY5. |
| 418 | 10322408 | Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of Type 2 diabetes characterized by early onset, autosomal dominant inheritance and primary defects in insulin secretion. |
| 419 | 10322408 | To date, five proteins have been identified whose genetic absence or impairment causes MODY, the enzyme glucokinase (GCK/MODY2) and four transcription factors: hepatocyte nuclear factor 4alpha (HNF-4alpha/MODY1), HNF-1alpha/MODY3, insulin promoter factor 1 (IPF-1/MODY4) and HNF-1beta/MODY5. |
| 420 | 10331424 | Using the mutated human HNF-4alpha2, we have found that, in the absence of chicken ovalbumin upstream promoter transcription factor II (COUP TFII), the E276Q substitution does not significantly affect the dimerization and transactivating activities of HNF-4alpha, at least on the promoters studied herein. |
| 421 | 10331424 | The impaired synergy between COUP TFII and HNF-4 on the HNF-1 promoter results from an alteration of their interaction. |
| 422 | 10331424 | Using the mutated human HNF-4alpha2, we have found that, in the absence of chicken ovalbumin upstream promoter transcription factor II (COUP TFII), the E276Q substitution does not significantly affect the dimerization and transactivating activities of HNF-4alpha, at least on the promoters studied herein. |
| 423 | 10331424 | The impaired synergy between COUP TFII and HNF-4 on the HNF-1 promoter results from an alteration of their interaction. |
| 424 | 10334325 | Mutation in the HNF-4alpha gene affects insulin secretion and triglyceride metabolism. |
| 425 | 10389854 | The functional properties of mutant HNF-4alpha proteins and the molecular mechanisms by which they impair insulin secretion are largely unknown. |
| 426 | 10417964 | To date, mutations in genes of five proteins have been shown to cause MODY: glucokinase (MODY2), hepatic nuclear factor-1 alpha (HNF-1 alpha) (MODY3), hepatic nuclear factor-4 alpha (HNF-4 alpha) (MODY1), insulin promoter factor 1 (IPF-1) (MODY4) and hepatic nuclear factor-1 beta (HNF-1 beta) (MODY5), but other MODY genes still await elucidation. |
| 427 | 10482964 | The most common cause of maturity-onset diabetes of the young (MODY) is a mutation in the hepatic nuclear factor 1alpha (HNF1alpha) gene (MODY3). |
| 428 | 10484768 | Mutations in the homeodomain-containing transcription factor hepatocyte nuclear factor (HNF)-1beta are the cause of one form of maturity-onset diabetes of the young (MODY), type 5 (MODY5). |
| 429 | 10484768 | These studies strongly suggest that heterozygous mutations in the HNF-1beta gene are associated with a syndrome characterized by MODY and severe, non-diabetic renal disease. |
| 430 | 10484768 | Mutations in the homeodomain-containing transcription factor hepatocyte nuclear factor (HNF)-1beta are the cause of one form of maturity-onset diabetes of the young (MODY), type 5 (MODY5). |
| 431 | 10484768 | These studies strongly suggest that heterozygous mutations in the HNF-1beta gene are associated with a syndrome characterized by MODY and severe, non-diabetic renal disease. |
| 432 | 10491332 | Human insulin gene is a target gene of hepatocyte nuclear factor-1alpha (HNF-1alpha) and HNF-1beta. |
| 433 | 10491332 | Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes characterized by autosomal dominant inheritance, early-onset, and impaired insulin secretion. |
| 434 | 10491332 | The type 3 and type 5 forms of MODY result from mutations in the genes encoding the transcription factor, hepatocyte nuclear factor (HNF)-1alpha and HNF-1beta, respectively. |
| 435 | 10491332 | We studied the effects of wild-type and four mutant (L12H, R263C, P379fsdelCT, and L584S585fsinsTC) HNF-1alpha, which were identified in Japanese subjects with MODY3 on human insulin gene transcription. |
| 436 | 10491332 | Both wild-type (WT) HNF-1alpha and HNF-1beta bound to the oligonucleotide containing the A3 element sequence in the human insulin promoter and transactivated the insulin-luciferase reporter gene by 30- and 31-fold, respectively. |
| 437 | 10491332 | These data suggest that the insulin gene is a candidate target gene of HNF-1alpha/HNF-1beta and the impairment of insulin gene transcription by mutations in the HNF-1 gene might be involved in the pathogenesis of MODY. |
| 438 | 10491332 | Human insulin gene is a target gene of hepatocyte nuclear factor-1alpha (HNF-1alpha) and HNF-1beta. |
| 439 | 10491332 | Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes characterized by autosomal dominant inheritance, early-onset, and impaired insulin secretion. |
| 440 | 10491332 | The type 3 and type 5 forms of MODY result from mutations in the genes encoding the transcription factor, hepatocyte nuclear factor (HNF)-1alpha and HNF-1beta, respectively. |
| 441 | 10491332 | We studied the effects of wild-type and four mutant (L12H, R263C, P379fsdelCT, and L584S585fsinsTC) HNF-1alpha, which were identified in Japanese subjects with MODY3 on human insulin gene transcription. |
| 442 | 10491332 | Both wild-type (WT) HNF-1alpha and HNF-1beta bound to the oligonucleotide containing the A3 element sequence in the human insulin promoter and transactivated the insulin-luciferase reporter gene by 30- and 31-fold, respectively. |
| 443 | 10491332 | These data suggest that the insulin gene is a candidate target gene of HNF-1alpha/HNF-1beta and the impairment of insulin gene transcription by mutations in the HNF-1 gene might be involved in the pathogenesis of MODY. |
| 444 | 10491332 | Human insulin gene is a target gene of hepatocyte nuclear factor-1alpha (HNF-1alpha) and HNF-1beta. |
| 445 | 10491332 | Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes characterized by autosomal dominant inheritance, early-onset, and impaired insulin secretion. |
| 446 | 10491332 | The type 3 and type 5 forms of MODY result from mutations in the genes encoding the transcription factor, hepatocyte nuclear factor (HNF)-1alpha and HNF-1beta, respectively. |
| 447 | 10491332 | We studied the effects of wild-type and four mutant (L12H, R263C, P379fsdelCT, and L584S585fsinsTC) HNF-1alpha, which were identified in Japanese subjects with MODY3 on human insulin gene transcription. |
| 448 | 10491332 | Both wild-type (WT) HNF-1alpha and HNF-1beta bound to the oligonucleotide containing the A3 element sequence in the human insulin promoter and transactivated the insulin-luciferase reporter gene by 30- and 31-fold, respectively. |
| 449 | 10491332 | These data suggest that the insulin gene is a candidate target gene of HNF-1alpha/HNF-1beta and the impairment of insulin gene transcription by mutations in the HNF-1 gene might be involved in the pathogenesis of MODY. |
| 450 | 10588527 | Molecular genetics of diabetes mellitus in Chinese subjects: identification of mutations in glucokinase and hepatocyte nuclear factor-1alpha genes in patients with early-onset type 2 diabetes mellitus/MODY. |
| 451 | 10606640 | A MODY3-associated mutation in the HNF1alpha gene, a well-known target gene of HNF4alpha, results in a dramatic loss of the HNF4 binding site in the promoter, indicating that mutations in the HNF4alpha gene might cause MODY through impaired HNF1alpha gene function. |
| 452 | 10609119 | These genes encode hepatocyte nuclear factor-4 alpha (HNF-4 alpha, MODY1), glucokinase (MODY2), hepatocyte nuclear factor-1 alpha (HNF-1 alpha, MODY3), insulin promoter factor-1 (IPF-1, MODY4), and hepatocyte nuclear factor-1 beta (HNF-1 beta, MODY5). |
| 453 | 10634407 | Mutations in the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene are the cause of maturity-onset diabetes of the young type 3 (MODY 3), which is characterized by a severe impairment of insulin secretion and early onset of the disease. |
| 454 | 10634407 | From a large population-based sample of unrelated Japanese patients with type 1 diabetes, 28 patients who lacked autoantibodies to glutamic acid decarboxylase, islet cell antigen 512/insulinoma-associated antigen-2, phogrin (phosphate homolog of granules of insulinoma)/insulinoma-associated antigen-2beta, and insulin at the onset of type 1 diabetes were examined by PCR-based direct sequencing of the 10 exons, flanking introns, and the promoter region of the HNF-1alpha gene. |
| 455 | 10690901 | Several studies have identified evidence for linkage between type 2 diabetes and the regions on chromosomes 12 and 20 containing the maturity-onset diabetes of the young (MODY) genes, hepatocyte nuclear factor-1alpha (HNF-1alpha) and HNF-4alpha. |
| 456 | 10690901 | Loci contributing sibling recurrence risks, relative to the general population risk, of 1.75 and 1.25 could be excluded for the HNF-1alpha and HNF-4alpha regions, respectively. |
| 457 | 10690901 | Several studies have identified evidence for linkage between type 2 diabetes and the regions on chromosomes 12 and 20 containing the maturity-onset diabetes of the young (MODY) genes, hepatocyte nuclear factor-1alpha (HNF-1alpha) and HNF-4alpha. |
| 458 | 10690901 | Loci contributing sibling recurrence risks, relative to the general population risk, of 1.75 and 1.25 could be excluded for the HNF-1alpha and HNF-4alpha regions, respectively. |
| 459 | 10694920 | Three novel missense mutations in the glucokinase gene (G80S; E221K; G227C) in Italian subjects with maturity-onset diabetes of the young (MODY). |
| 460 | 10694920 | The maturity-onset diabetes of the young (MODY), an autosomal dominant form of non-insulin dependent diabetes mellitus (NIDDM), is caused by mutations in the glucokinase (GK, MODY 2) and in the hepatocyte nuclear factor 1a (MODY 3) and 4a (MODY 1) genes. |
| 461 | 10694920 | We have screened the glucokinase gene by the polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) in fifteen subjects with clinical characteristics of MODY and one parent with NIDDM, impaired glucose tolerance or gestational diabetes. |
| 462 | 10694920 | Three novel missense mutations in the glucokinase gene (G80S; E221K; G227C) in Italian subjects with maturity-onset diabetes of the young (MODY). |
| 463 | 10694920 | The maturity-onset diabetes of the young (MODY), an autosomal dominant form of non-insulin dependent diabetes mellitus (NIDDM), is caused by mutations in the glucokinase (GK, MODY 2) and in the hepatocyte nuclear factor 1a (MODY 3) and 4a (MODY 1) genes. |
| 464 | 10694920 | We have screened the glucokinase gene by the polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) in fifteen subjects with clinical characteristics of MODY and one parent with NIDDM, impaired glucose tolerance or gestational diabetes. |
| 465 | 10694920 | Three novel missense mutations in the glucokinase gene (G80S; E221K; G227C) in Italian subjects with maturity-onset diabetes of the young (MODY). |
| 466 | 10694920 | The maturity-onset diabetes of the young (MODY), an autosomal dominant form of non-insulin dependent diabetes mellitus (NIDDM), is caused by mutations in the glucokinase (GK, MODY 2) and in the hepatocyte nuclear factor 1a (MODY 3) and 4a (MODY 1) genes. |
| 467 | 10694920 | We have screened the glucokinase gene by the polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) in fifteen subjects with clinical characteristics of MODY and one parent with NIDDM, impaired glucose tolerance or gestational diabetes. |
| 468 | 10720084 | Maturity-onset diabetes of the young (MODY) now exists in five subtypes (MODY1-5), four of which are caused by mutations in transcription factors hepatocyte nuclear factor-4alpha (HNF-4alpha), HNF-1alpha, insulin promoter factor-1 (IPF-1), and HNF-1beta (MODY1, -3, -4, and -5). |
| 469 | 10720084 | Thus, highlighting the potential role of this transcription factor in the genetic basis of Danish and Italian MODY as well as in Danish patients with late-onset type 2 diabetes mellitus, we have examined the human IPF-1 gene for mutations by single strand conformation polymorphism and heteroduplex analysis in 200 Danish patients with late-onset type 2 diabetes and in 44 Danish and Italian MODY patients. |
| 470 | 10720084 | We conclude that variants in IPF-1 are not a common cause of MODY or late-onset type 2 diabetes in the Caucasian population, and that in terms of insulin transcription both the N76 and the T140 mutations are likely to represent functionally normal IPF-1 variants with no direct role in the pathogenesis of MODY or late-onset type 2 diabetes mellitus. |
| 471 | 10720084 | Maturity-onset diabetes of the young (MODY) now exists in five subtypes (MODY1-5), four of which are caused by mutations in transcription factors hepatocyte nuclear factor-4alpha (HNF-4alpha), HNF-1alpha, insulin promoter factor-1 (IPF-1), and HNF-1beta (MODY1, -3, -4, and -5). |
| 472 | 10720084 | Thus, highlighting the potential role of this transcription factor in the genetic basis of Danish and Italian MODY as well as in Danish patients with late-onset type 2 diabetes mellitus, we have examined the human IPF-1 gene for mutations by single strand conformation polymorphism and heteroduplex analysis in 200 Danish patients with late-onset type 2 diabetes and in 44 Danish and Italian MODY patients. |
| 473 | 10720084 | We conclude that variants in IPF-1 are not a common cause of MODY or late-onset type 2 diabetes in the Caucasian population, and that in terms of insulin transcription both the N76 and the T140 mutations are likely to represent functionally normal IPF-1 variants with no direct role in the pathogenesis of MODY or late-onset type 2 diabetes mellitus. |
| 474 | 10720084 | Maturity-onset diabetes of the young (MODY) now exists in five subtypes (MODY1-5), four of which are caused by mutations in transcription factors hepatocyte nuclear factor-4alpha (HNF-4alpha), HNF-1alpha, insulin promoter factor-1 (IPF-1), and HNF-1beta (MODY1, -3, -4, and -5). |
| 475 | 10720084 | Thus, highlighting the potential role of this transcription factor in the genetic basis of Danish and Italian MODY as well as in Danish patients with late-onset type 2 diabetes mellitus, we have examined the human IPF-1 gene for mutations by single strand conformation polymorphism and heteroduplex analysis in 200 Danish patients with late-onset type 2 diabetes and in 44 Danish and Italian MODY patients. |
| 476 | 10720084 | We conclude that variants in IPF-1 are not a common cause of MODY or late-onset type 2 diabetes in the Caucasian population, and that in terms of insulin transcription both the N76 and the T140 mutations are likely to represent functionally normal IPF-1 variants with no direct role in the pathogenesis of MODY or late-onset type 2 diabetes mellitus. |
| 477 | 10768087 | This has been shown to be the primary cause of the disease in the various forms of maturity-onset diabetes of the young (MODY) and has also been implicated in adult-onset Type II (non-insulin-dependent) diabetes mellitus. |
| 478 | 10793405 | Only a minority of cases of type 2 diabetes are caused by a single-gene defect, such as maturity-onset diabetes of youth (mutated MODY gene), syndrome of insulin resistance (insulin receptor defect), and maternally inherited diabetes and deafness (mitochondrial gene defect). |
| 479 | 10866048 | Reduced pancreatic polypeptide response to hypoglycemia and amylin response to arginine in subjects with a mutation in the HNF-4alpha/MODY1 gene. |
| 480 | 10866048 | Subjects with the Q268X mutation in the hepatocyte nuclear factor (HNF)-4alpha gene (RW pedigree/maturity-onset diabetes of the young [MODY]-1) have diminished insulin and glucagon secretory responses to arginine. |
| 481 | 10866048 | To determine if pancreatic polypeptide (PP) secretion is likewise involved, we studied PP responses to insulin-induced hypoglycemia in 17 RW pedigree members: 6 nondiabetic mutation-negative [ND(-)], 4 nondiabetic mutation-positive [ND(+)], and 7 diabetic mutation-positive [D(+)]. |
| 482 | 10866048 | These results suggest that the HNF-4alpha mutation in the RW/MODY1 pedigree confers a generalized defect in islet cell function involving PP cells in addition to beta- and alpha-cells, and beta-cell impairment involving proportional deficits in insulin and amylin secretion. |
| 483 | 10866048 | Reduced pancreatic polypeptide response to hypoglycemia and amylin response to arginine in subjects with a mutation in the HNF-4alpha/MODY1 gene. |
| 484 | 10866048 | Subjects with the Q268X mutation in the hepatocyte nuclear factor (HNF)-4alpha gene (RW pedigree/maturity-onset diabetes of the young [MODY]-1) have diminished insulin and glucagon secretory responses to arginine. |
| 485 | 10866048 | To determine if pancreatic polypeptide (PP) secretion is likewise involved, we studied PP responses to insulin-induced hypoglycemia in 17 RW pedigree members: 6 nondiabetic mutation-negative [ND(-)], 4 nondiabetic mutation-positive [ND(+)], and 7 diabetic mutation-positive [D(+)]. |
| 486 | 10866048 | These results suggest that the HNF-4alpha mutation in the RW/MODY1 pedigree confers a generalized defect in islet cell function involving PP cells in addition to beta- and alpha-cells, and beta-cell impairment involving proportional deficits in insulin and amylin secretion. |
| 487 | 10866048 | Reduced pancreatic polypeptide response to hypoglycemia and amylin response to arginine in subjects with a mutation in the HNF-4alpha/MODY1 gene. |
| 488 | 10866048 | Subjects with the Q268X mutation in the hepatocyte nuclear factor (HNF)-4alpha gene (RW pedigree/maturity-onset diabetes of the young [MODY]-1) have diminished insulin and glucagon secretory responses to arginine. |
| 489 | 10866048 | To determine if pancreatic polypeptide (PP) secretion is likewise involved, we studied PP responses to insulin-induced hypoglycemia in 17 RW pedigree members: 6 nondiabetic mutation-negative [ND(-)], 4 nondiabetic mutation-positive [ND(+)], and 7 diabetic mutation-positive [D(+)]. |
| 490 | 10866048 | These results suggest that the HNF-4alpha mutation in the RW/MODY1 pedigree confers a generalized defect in islet cell function involving PP cells in addition to beta- and alpha-cells, and beta-cell impairment involving proportional deficits in insulin and amylin secretion. |
| 491 | 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). |
| 492 | 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. |
| 493 | 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). |
| 494 | 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. |
| 495 | 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. |
| 496 | 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. |
| 497 | 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. |
| 498 | 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. |
| 499 | 10899756 | Gene expression studies have shown that HNF3 proteins are critical regulators of the early-onset type 2 diabetes genes HNF-1 alpha, HNF-4 alpha and IPF-1/PDX-1 (MODY3, 1 and 4, respectively) and of glucagon transcription and pancreatic alpha-cell function. |
| 500 | 10905494 | Genotype/phenotype relationships in HNF-4alpha/MODY1: haploinsufficiency is associated with reduced apolipoprotein (AII), apolipoprotein (CIII), lipoprotein(a), and triglyceride levels. |
| 501 | 10905494 | Heterozygous mutations in the HNF-4alpha gene are responsible for maturity-onset diabetes of the young 1 (MODY1), which is characterized by pancreatic beta-cell-deficient insulin secretion. |
| 502 | 10905494 | In this study, we have identified HNF-4alpha target genes that are mainly expressed in the liver, including alpha1-antitrypsin, alpha1-antichymotrypsin, alpha-fetal protein, ceruloplasmin, IGF binding protein 1, transferrin, apolipoprotein(AI) [apo(AI)], apo(AII), apo(B), and apo(CIII). |
| 503 | 10905494 | Genotype/phenotype relationships in HNF-4alpha/MODY1: haploinsufficiency is associated with reduced apolipoprotein (AII), apolipoprotein (CIII), lipoprotein(a), and triglyceride levels. |
| 504 | 10905494 | Heterozygous mutations in the HNF-4alpha gene are responsible for maturity-onset diabetes of the young 1 (MODY1), which is characterized by pancreatic beta-cell-deficient insulin secretion. |
| 505 | 10905494 | In this study, we have identified HNF-4alpha target genes that are mainly expressed in the liver, including alpha1-antitrypsin, alpha1-antichymotrypsin, alpha-fetal protein, ceruloplasmin, IGF binding protein 1, transferrin, apolipoprotein(AI) [apo(AI)], apo(AII), apo(B), and apo(CIII). |
| 506 | 10905494 | Genotype/phenotype relationships in HNF-4alpha/MODY1: haploinsufficiency is associated with reduced apolipoprotein (AII), apolipoprotein (CIII), lipoprotein(a), and triglyceride levels. |
| 507 | 10905494 | Heterozygous mutations in the HNF-4alpha gene are responsible for maturity-onset diabetes of the young 1 (MODY1), which is characterized by pancreatic beta-cell-deficient insulin secretion. |
| 508 | 10905494 | In this study, we have identified HNF-4alpha target genes that are mainly expressed in the liver, including alpha1-antitrypsin, alpha1-antichymotrypsin, alpha-fetal protein, ceruloplasmin, IGF binding protein 1, transferrin, apolipoprotein(AI) [apo(AI)], apo(AII), apo(B), and apo(CIII). |
| 509 | 10922486 | In the liver of streptozotocin-induced diabetic rat, mRNA and protein levels for HNF-4alpha were elevated, and were normalized by insulin treatment. |
| 510 | 10940385 | Since pancreatic beta-cell dysfunction is a feature of MODY1 patients, we compared the functional properties of the R154X mutant in insulin-secreting pancreatic beta-cells and non-beta-cells. |
| 511 | 10943822 | Mutations in hepatocyte nuclear factor-4alpha, hepatocyte nuclear factor-1alpha, insulin promoter factor-1 and hepatocyte nuclear factor-1beta, respectively, cause MODY1, MODY3, MODY4, and MODY5. |
| 512 | 10946909 | Variability of the insulin receptor substrate-1, hepatocyte nuclear factor-1alpha (HNF-1alpha), HNF-4alpha, and HNF-6 genes and size at birth in a population-based sample of young Danish subjects. |
| 513 | 10946909 | The Gly/Arg972 of insulin receptor substrate-1 (IRS-1), the Thr/Ile130 of the hepatocyte nuclear factor-4alpha (HNF-4alpha), the Pro/Ala75 of HNF-6, and the Ile/Leu27, Ala/Val93, and Ser/Asn4s7 polymorphisms of the HNF-lalpha gene were examined for association with birth weight and length and the ponderal index. |
| 514 | 10946909 | In conclusion, common variability in the genes encoding the IRS-1, HNF-lalpha, HNF-4alpha, and HNF-6 proteins can be excluded as major factors influencing size at birth among Danish Caucasian subjects. |
| 515 | 10946909 | Variability of the insulin receptor substrate-1, hepatocyte nuclear factor-1alpha (HNF-1alpha), HNF-4alpha, and HNF-6 genes and size at birth in a population-based sample of young Danish subjects. |
| 516 | 10946909 | The Gly/Arg972 of insulin receptor substrate-1 (IRS-1), the Thr/Ile130 of the hepatocyte nuclear factor-4alpha (HNF-4alpha), the Pro/Ala75 of HNF-6, and the Ile/Leu27, Ala/Val93, and Ser/Asn4s7 polymorphisms of the HNF-lalpha gene were examined for association with birth weight and length and the ponderal index. |
| 517 | 10946909 | In conclusion, common variability in the genes encoding the IRS-1, HNF-lalpha, HNF-4alpha, and HNF-6 proteins can be excluded as major factors influencing size at birth among Danish Caucasian subjects. |
| 518 | 10946909 | Variability of the insulin receptor substrate-1, hepatocyte nuclear factor-1alpha (HNF-1alpha), HNF-4alpha, and HNF-6 genes and size at birth in a population-based sample of young Danish subjects. |
| 519 | 10946909 | The Gly/Arg972 of insulin receptor substrate-1 (IRS-1), the Thr/Ile130 of the hepatocyte nuclear factor-4alpha (HNF-4alpha), the Pro/Ala75 of HNF-6, and the Ile/Leu27, Ala/Val93, and Ser/Asn4s7 polymorphisms of the HNF-lalpha gene were examined for association with birth weight and length and the ponderal index. |
| 520 | 10946909 | In conclusion, common variability in the genes encoding the IRS-1, HNF-lalpha, HNF-4alpha, and HNF-6 proteins can be excluded as major factors influencing size at birth among Danish Caucasian subjects. |
| 521 | 10953613 | Mutations in the glucokinase gene and the genes for the transcription factors HNF-1 alpha, HNF-4 alpha, IPF-1, HNF-1 beta y HNF-3 beta have been demonstrated to cause MODY, a subtype of NIDDM characterized by autosomal dominate pattern of inheritance and an early-onset. |
| 522 | 10953613 | Mutations in any of the genes associated to MODY may contribute to the insulin secretion deficiency frequently observed in early-onset type 2 diabetic patients. |
| 523 | 10953613 | Mutations in the glucokinase gene and the genes for the transcription factors HNF-1 alpha, HNF-4 alpha, IPF-1, HNF-1 beta y HNF-3 beta have been demonstrated to cause MODY, a subtype of NIDDM characterized by autosomal dominate pattern of inheritance and an early-onset. |
| 524 | 10953613 | Mutations in any of the genes associated to MODY may contribute to the insulin secretion deficiency frequently observed in early-onset type 2 diabetic patients. |
| 525 | 10967107 | During pancreatic development, the paired homeodomain transcription factor PAX4 is required for the differentiation of the insulin-producing beta cells and somatostatin-producing delta cells. |
| 526 | 10967107 | Serial deletions through this region reveal the presence of positive elements that bind several pancreatic transcription factors as follows: the POU homeodomain factor HNF1alpha, the orphan nuclear receptor HNF4alpha, the homeodomain factor PDX1, and a heterodimer composed of two basic helix-loop-helix factors. |
| 527 | 10967120 | Mutations in the HNF4alpha gene are associated with the subtype 1 of maturity-onset diabetes of the young (MODY1), which is characterized by impaired insulin secretory response to glucose in pancreatic beta-cells. |
| 528 | 10967120 | The tetracycline-inducible system was employed to achieve tightly controlled expression of both wild type (WT) and dominant-negative mutant (DN) of HNF4alpha in INS-1 cells. |
| 529 | 10967120 | Quantitative evaluation of HNF4alpha-regulated pancreatic beta-cell gene expression revealed altered mRNA levels of insulin, glucose transporter-2, L-pyruvate kinase, aldolase B, 2-oxoglutarate dehydrogenase E1 subunit, and mitochondrial uncoupling protein-2. |
| 530 | 10967120 | Indeed, HNF4alpha changed the HNF1alpha mRNA levels and HNF1alpha promoter luciferase activity through altered HNF4alpha binding. |
| 531 | 10967120 | Mutations in the HNF4alpha gene are associated with the subtype 1 of maturity-onset diabetes of the young (MODY1), which is characterized by impaired insulin secretory response to glucose in pancreatic beta-cells. |
| 532 | 10967120 | The tetracycline-inducible system was employed to achieve tightly controlled expression of both wild type (WT) and dominant-negative mutant (DN) of HNF4alpha in INS-1 cells. |
| 533 | 10967120 | Quantitative evaluation of HNF4alpha-regulated pancreatic beta-cell gene expression revealed altered mRNA levels of insulin, glucose transporter-2, L-pyruvate kinase, aldolase B, 2-oxoglutarate dehydrogenase E1 subunit, and mitochondrial uncoupling protein-2. |
| 534 | 10967120 | Indeed, HNF4alpha changed the HNF1alpha mRNA levels and HNF1alpha promoter luciferase activity through altered HNF4alpha binding. |
| 535 | 10967120 | Mutations in the HNF4alpha gene are associated with the subtype 1 of maturity-onset diabetes of the young (MODY1), which is characterized by impaired insulin secretory response to glucose in pancreatic beta-cells. |
| 536 | 10967120 | The tetracycline-inducible system was employed to achieve tightly controlled expression of both wild type (WT) and dominant-negative mutant (DN) of HNF4alpha in INS-1 cells. |
| 537 | 10967120 | Quantitative evaluation of HNF4alpha-regulated pancreatic beta-cell gene expression revealed altered mRNA levels of insulin, glucose transporter-2, L-pyruvate kinase, aldolase B, 2-oxoglutarate dehydrogenase E1 subunit, and mitochondrial uncoupling protein-2. |
| 538 | 10967120 | Indeed, HNF4alpha changed the HNF1alpha mRNA levels and HNF1alpha promoter luciferase activity through altered HNF4alpha binding. |
| 539 | 10980542 | Proposed mechanism for a novel insertion/deletion frameshift mutation (I414G415ATCG-->CCA) in the hepatocyte nuclear factor 1 alpha (HNF-1 alpha) gene which causes maturity-onset diabetes of the young (MODY). |
| 540 | 10980542 | Maturity-onset diabetes of the young (MODY) is a monogenic subgroup of non-insulin dependent diabetes (NIDDM) characterized by an early age of diagnosis (usually < 25 years) and an autosomal dominant mode of inheritance. |
| 541 | 10980542 | Mutations in the hepatocyte nuclear factor 1 alpha (HNF-1alpha) [MODY3] gene represent the most common cause of MODY in the UK and a common cause of MODY in many other populations. |
| 542 | 10980542 | Proposed mechanism for a novel insertion/deletion frameshift mutation (I414G415ATCG-->CCA) in the hepatocyte nuclear factor 1 alpha (HNF-1 alpha) gene which causes maturity-onset diabetes of the young (MODY). |
| 543 | 10980542 | Maturity-onset diabetes of the young (MODY) is a monogenic subgroup of non-insulin dependent diabetes (NIDDM) characterized by an early age of diagnosis (usually < 25 years) and an autosomal dominant mode of inheritance. |
| 544 | 10980542 | Mutations in the hepatocyte nuclear factor 1 alpha (HNF-1alpha) [MODY3] gene represent the most common cause of MODY in the UK and a common cause of MODY in many other populations. |
| 545 | 10980542 | Proposed mechanism for a novel insertion/deletion frameshift mutation (I414G415ATCG-->CCA) in the hepatocyte nuclear factor 1 alpha (HNF-1 alpha) gene which causes maturity-onset diabetes of the young (MODY). |
| 546 | 10980542 | Maturity-onset diabetes of the young (MODY) is a monogenic subgroup of non-insulin dependent diabetes (NIDDM) characterized by an early age of diagnosis (usually < 25 years) and an autosomal dominant mode of inheritance. |
| 547 | 10980542 | Mutations in the hepatocyte nuclear factor 1 alpha (HNF-1alpha) [MODY3] gene represent the most common cause of MODY in the UK and a common cause of MODY in many other populations. |
| 548 | 10983627 | To investigate the possibility that the HNF-4alpha gene contributes to the onset of non-insulin-dependent diabetes mellitus (NIDDM) in Japanese patients, we screened all exons and flanking introns of this gene for mutations in 100 patients with NIDDM diagnosed after 25 years of age. |
| 549 | 10990086 | No diabetes-associated mutations in the coding region of the hepatocyte nuclear factor-4gamma gene (HNF4G) in Japanese patients with MODY. |
| 550 | 10993727 | Hepatocyte nuclear factor 4alpha (HNF4alpha) (NR2A1), an orphan member of the nuclear receptor superfamily, binds DNA exclusively as a homodimer even though it is very similar in amino acid sequence to retinoid X receptor alpha (RXRalpha), which heterodimerizes readily with other receptors. |
| 551 | 10993727 | When K300 (in helix 9) and E327 (in helix 10) of HNF4alpha1 were converted to the analogous residues in RXRalpha (E390 and K417, respectively) the resulting construct did not heterodimerize with the wild-type HNF4alpha, although it was still able to form homodimers and bind DNA. |
| 552 | 10993727 | Furthermore, the double mutant did not heterodimerize with RXR or RAR but was still able to dimerize in solution with an HNF4alpha construct truncated at amino acid residue 268. |
| 553 | 10993727 | Hepatocyte nuclear factor 4alpha (HNF4alpha) (NR2A1), an orphan member of the nuclear receptor superfamily, binds DNA exclusively as a homodimer even though it is very similar in amino acid sequence to retinoid X receptor alpha (RXRalpha), which heterodimerizes readily with other receptors. |
| 554 | 10993727 | When K300 (in helix 9) and E327 (in helix 10) of HNF4alpha1 were converted to the analogous residues in RXRalpha (E390 and K417, respectively) the resulting construct did not heterodimerize with the wild-type HNF4alpha, although it was still able to form homodimers and bind DNA. |
| 555 | 10993727 | Furthermore, the double mutant did not heterodimerize with RXR or RAR but was still able to dimerize in solution with an HNF4alpha construct truncated at amino acid residue 268. |
| 556 | 10993727 | Hepatocyte nuclear factor 4alpha (HNF4alpha) (NR2A1), an orphan member of the nuclear receptor superfamily, binds DNA exclusively as a homodimer even though it is very similar in amino acid sequence to retinoid X receptor alpha (RXRalpha), which heterodimerizes readily with other receptors. |
| 557 | 10993727 | When K300 (in helix 9) and E327 (in helix 10) of HNF4alpha1 were converted to the analogous residues in RXRalpha (E390 and K417, respectively) the resulting construct did not heterodimerize with the wild-type HNF4alpha, although it was still able to form homodimers and bind DNA. |
| 558 | 10993727 | Furthermore, the double mutant did not heterodimerize with RXR or RAR but was still able to dimerize in solution with an HNF4alpha construct truncated at amino acid residue 268. |
| 559 | 11058894 | MODY is genetically heterogeneous with five different genes identified to date: hepatocyte nuclear factor-4 alpha (HNF-4 alpha) [MODY1]; glucokinase [MODY2]; hepatocyte nuclear factor-1 alpha (HNF-1 alpha) [MODY3]; insulin promoter factor-1 (IPF-1) [MODY4]; and hepatocyte nuclear factor-1 beta (HNF-1 beta) [MODY5]. |
| 560 | 11058894 | Mutations in the HNF-1 alpha gene represent a common cause of MODY in the majority of populations studied. |
| 561 | 11058894 | The identification of an HNF-1 alpha gene mutation in a patient with type 2 diabetes confirms the diagnosis of MODY and has important implications for clinical management. |
| 562 | 11058894 | MODY is genetically heterogeneous with five different genes identified to date: hepatocyte nuclear factor-4 alpha (HNF-4 alpha) [MODY1]; glucokinase [MODY2]; hepatocyte nuclear factor-1 alpha (HNF-1 alpha) [MODY3]; insulin promoter factor-1 (IPF-1) [MODY4]; and hepatocyte nuclear factor-1 beta (HNF-1 beta) [MODY5]. |
| 563 | 11058894 | Mutations in the HNF-1 alpha gene represent a common cause of MODY in the majority of populations studied. |
| 564 | 11058894 | The identification of an HNF-1 alpha gene mutation in a patient with type 2 diabetes confirms the diagnosis of MODY and has important implications for clinical management. |
| 565 | 11058894 | MODY is genetically heterogeneous with five different genes identified to date: hepatocyte nuclear factor-4 alpha (HNF-4 alpha) [MODY1]; glucokinase [MODY2]; hepatocyte nuclear factor-1 alpha (HNF-1 alpha) [MODY3]; insulin promoter factor-1 (IPF-1) [MODY4]; and hepatocyte nuclear factor-1 beta (HNF-1 beta) [MODY5]. |
| 566 | 11058894 | Mutations in the HNF-1 alpha gene represent a common cause of MODY in the majority of populations studied. |
| 567 | 11058894 | The identification of an HNF-1 alpha gene mutation in a patient with type 2 diabetes confirms the diagnosis of MODY and has important implications for clinical management. |
| 568 | 11078465 | beta-cell transcription factors and diabetes: no evidence for diabetes-associated mutations in the gene encoding the basic helix-loop-helix transcription factor neurogenic differentiation 4 (NEUROD4) in Japanese patients with MODY. |
| 569 | 11078465 | We have screened 57 unrelated Japanese subjects with a clinical diagnosis of MODY for mutations in the NeuroD4/Math-3/ATH-3 gene (NEUROD4). |
| 570 | 11136233 | The ability of the orphan nuclear receptor small heterodimer partner (SHP, NR0B2) to modulate the transcriptional activity of MODY1 protein, the nuclear receptor HNF-4alpha, suggested SHP as a candidate MODY gene. |
| 571 | 11162430 | During a screening of Norwegian patients with suspected MODY we identified two novel HNF-1alpha mutations, P112L and Q466X. |
| 572 | 11202217 | The subgroups that result in non-insulin-dependent DM in children are as follows: the 'honeymoon' phase of type 1 DM, type 2 DM, genetic syndromes accompanied by DM, and maturity-onset diabetes of the young (MODY). |
| 573 | 11202217 | It should be emphasized that MODY comprises two discrete clinical syndromes: glucokinase diabetes and transcription factor diabetes, the latter of which results from mutations in the genes encoding hepatocyte nuclear factor (HNF)-1alpha, HNF-1beta, HNF-4alpha and insulin promoter factor-1. |
| 574 | 11202217 | The subgroups that result in non-insulin-dependent DM in children are as follows: the 'honeymoon' phase of type 1 DM, type 2 DM, genetic syndromes accompanied by DM, and maturity-onset diabetes of the young (MODY). |
| 575 | 11202217 | It should be emphasized that MODY comprises two discrete clinical syndromes: glucokinase diabetes and transcription factor diabetes, the latter of which results from mutations in the genes encoding hepatocyte nuclear factor (HNF)-1alpha, HNF-1beta, HNF-4alpha and insulin promoter factor-1. |
| 576 | 11215856 | After excluding 14 subjects with pancreatic calcification, Wolfram's syndrome, MODY or mitochondrial gene mutation, 45 (57.0%) were found to be insulin-deficient and 34 (43.0%) were insulin-sufficient based on post-glucagon C-peptide levels. |
| 577 | 11232004 | Among this group we found two individuals carrying missense mutations in exon 4 of the hepatocyte nuclear factor-1alpha (HNF-4alpha) gene (Asp(126)-->His/Tyr and Arg(154)-->Gln, respectively) and one carrying a nonsense mutation in exon 7 of the HNF-1alpha gene (Gln(486)-->stop codon); 7.5% had positive titers for glutamic acid decarboxylase antibodies. |
| 578 | 11232004 | Mutations in either the HNF-1alpha or the HNF-4alpha genes are present among the individuals who develop early-onset diabetes in our population. |
| 579 | 11232004 | Among this group we found two individuals carrying missense mutations in exon 4 of the hepatocyte nuclear factor-1alpha (HNF-4alpha) gene (Asp(126)-->His/Tyr and Arg(154)-->Gln, respectively) and one carrying a nonsense mutation in exon 7 of the HNF-1alpha gene (Gln(486)-->stop codon); 7.5% had positive titers for glutamic acid decarboxylase antibodies. |
| 580 | 11232004 | Mutations in either the HNF-1alpha or the HNF-4alpha genes are present among the individuals who develop early-onset diabetes in our population. |
| 581 | 11272165 | Mutations in the beta-cell genes encoding the glycolytic enzyme glucokinase (GCK) and the transcription factor hepatocyte nuclear factor (HNF)-1alpha are the most common causes of maturity-onset diabetes of the young (MODY). |
| 582 | 11272165 | We studied 178 U.K. and French MODY family members, including 45 GCK mutation carriers and 40 HNF-1alpha mutation carriers. |
| 583 | 11272165 | Homeostasis model assessment of fasting insulin and glucose showed reduced beta-cell function in both GCK (48% controls, P<0.0001) and HNF-1alpha (42% controls, P<0.0001). |
| 584 | 11272165 | Insulin sensitivity was similar to that of control subjects in the GCK subjects (93% controls, P = 0.78) but increased in the HNF-1alpha subjects (134.5% controls, P = 0.005). |
| 585 | 11272165 | Proinsulin-to-insulin ratios are increased in HNF-1alpha subjects (29.5%) but not in GCK (18.5%) subjects. |
| 586 | 11272165 | The defect in GCK is a stable defect of glucose sensing, whereas the HNF-1alpha mutation causes a progressive defect that alters beta-cell insulin secretion directly rather than the sensing of glucose. |
| 587 | 11272165 | Mutations in the beta-cell genes encoding the glycolytic enzyme glucokinase (GCK) and the transcription factor hepatocyte nuclear factor (HNF)-1alpha are the most common causes of maturity-onset diabetes of the young (MODY). |
| 588 | 11272165 | We studied 178 U.K. and French MODY family members, including 45 GCK mutation carriers and 40 HNF-1alpha mutation carriers. |
| 589 | 11272165 | Homeostasis model assessment of fasting insulin and glucose showed reduced beta-cell function in both GCK (48% controls, P<0.0001) and HNF-1alpha (42% controls, P<0.0001). |
| 590 | 11272165 | Insulin sensitivity was similar to that of control subjects in the GCK subjects (93% controls, P = 0.78) but increased in the HNF-1alpha subjects (134.5% controls, P = 0.005). |
| 591 | 11272165 | Proinsulin-to-insulin ratios are increased in HNF-1alpha subjects (29.5%) but not in GCK (18.5%) subjects. |
| 592 | 11272165 | The defect in GCK is a stable defect of glucose sensing, whereas the HNF-1alpha mutation causes a progressive defect that alters beta-cell insulin secretion directly rather than the sensing of glucose. |
| 593 | 11272211 | beta-Cell transcription factor genes are important in the pathophysiology of the beta-cell, with mutations in hepatocyte nuclear factor (HNF)-1alpha, HNF-4alpha, insulin promoter factor (IPF)-1, HNF-1beta, and NeuroD1/BETA2, all resulting in early-onset type 2 diabetes. |
| 594 | 11272211 | The relative distribution of the 90 families fitting maturity-onset diabetes of the young (MODY) criteria was 63% HNF-1alpha, 2% HNF-4alpha, 0% IPF-1, 1% HNF-1beta, 0% NeuroD1/ BETA2, and 20% glucokinase. |
| 595 | 11272211 | IPF-1 mutations are associated with a higher age at diagnosis (42.7 years) than HNF-1alpha (20.4 years), HNF-1beta (24.2 years), or HNF-4alpha (26.3 years) gene mutations. |
| 596 | 11272211 | beta-Cell transcription factor genes are important in the pathophysiology of the beta-cell, with mutations in hepatocyte nuclear factor (HNF)-1alpha, HNF-4alpha, insulin promoter factor (IPF)-1, HNF-1beta, and NeuroD1/BETA2, all resulting in early-onset type 2 diabetes. |
| 597 | 11272211 | The relative distribution of the 90 families fitting maturity-onset diabetes of the young (MODY) criteria was 63% HNF-1alpha, 2% HNF-4alpha, 0% IPF-1, 1% HNF-1beta, 0% NeuroD1/ BETA2, and 20% glucokinase. |
| 598 | 11272211 | IPF-1 mutations are associated with a higher age at diagnosis (42.7 years) than HNF-1alpha (20.4 years), HNF-1beta (24.2 years), or HNF-4alpha (26.3 years) gene mutations. |
| 599 | 11272211 | beta-Cell transcription factor genes are important in the pathophysiology of the beta-cell, with mutations in hepatocyte nuclear factor (HNF)-1alpha, HNF-4alpha, insulin promoter factor (IPF)-1, HNF-1beta, and NeuroD1/BETA2, all resulting in early-onset type 2 diabetes. |
| 600 | 11272211 | The relative distribution of the 90 families fitting maturity-onset diabetes of the young (MODY) criteria was 63% HNF-1alpha, 2% HNF-4alpha, 0% IPF-1, 1% HNF-1beta, 0% NeuroD1/ BETA2, and 20% glucokinase. |
| 601 | 11272211 | IPF-1 mutations are associated with a higher age at diagnosis (42.7 years) than HNF-1alpha (20.4 years), HNF-1beta (24.2 years), or HNF-4alpha (26.3 years) gene mutations. |
| 602 | 11293229 | These are hepatocyte nuclear factor (HNF)-4 alpha, HNF-1 alpha, insulin promoter factor (IPF)-1 and HNF-1 beta, which are associated with MODY1, 3, 4, 5 respectively. |
| 603 | 11293229 | HNF-1 beta (MODY5 locus on chromosome 17q) is a protein which forms heterodimers with HNF-1 alpha. |
| 604 | 11293229 | This rare form of diabetes has a clinical picture similar to MODY1 and MODY3. |
| 605 | 11293229 | BETA 2/Neurod1 has been recently associated with MODY by Dr Krolewski's group from Joslin Diabetes Center, Boston, MA, USA. |
| 606 | 11293229 | These are hepatocyte nuclear factor (HNF)-4 alpha, HNF-1 alpha, insulin promoter factor (IPF)-1 and HNF-1 beta, which are associated with MODY1, 3, 4, 5 respectively. |
| 607 | 11293229 | HNF-1 beta (MODY5 locus on chromosome 17q) is a protein which forms heterodimers with HNF-1 alpha. |
| 608 | 11293229 | This rare form of diabetes has a clinical picture similar to MODY1 and MODY3. |
| 609 | 11293229 | BETA 2/Neurod1 has been recently associated with MODY by Dr Krolewski's group from Joslin Diabetes Center, Boston, MA, USA. |
| 610 | 11293229 | These are hepatocyte nuclear factor (HNF)-4 alpha, HNF-1 alpha, insulin promoter factor (IPF)-1 and HNF-1 beta, which are associated with MODY1, 3, 4, 5 respectively. |
| 611 | 11293229 | HNF-1 beta (MODY5 locus on chromosome 17q) is a protein which forms heterodimers with HNF-1 alpha. |
| 612 | 11293229 | This rare form of diabetes has a clinical picture similar to MODY1 and MODY3. |
| 613 | 11293229 | BETA 2/Neurod1 has been recently associated with MODY by Dr Krolewski's group from Joslin Diabetes Center, Boston, MA, USA. |
| 614 | 11296231 | Transcription factor-dependent regulation of CBP and P/CAF histone acetyltransferase activity. |
| 615 | 11296231 | CREB-binding protein (CBP) and CBP-associated factor (P/CAF) are coactivators possessing an intrinsic histone acetyltransferase (HAT) activity. |
| 616 | 11296231 | Here we show that two dominant-negative mutants of hepatocyte nuclear factor-1alpha (HNF-1alpha), P447L and P519L, occurring in maturity onset diabetes of the young (MODY3) patients, exhibit paradoxically stronger interactions than the wild-type protein with either CBP or P/CAF. |
| 617 | 11296231 | However, CBP and P/CAF recruited by these mutants lack HAT activity. |
| 618 | 11296231 | In contrast, wild-type HNF-1alpha and other transcription factors, such as Sp1 or HNF-4, stimulated the HAT activity of CBP. |
| 619 | 11307309 | This form of diabetes can result from mutations in at least seven different genes: hepatocyte nuclear factor(HNF)-4 alpha/MODY1, glucokinase/MODY2, HNF-1 alpha/MODY3, insulin promoter factor(IPF-1)/MODY4, HNF-1 beta/MODY5, NeuroD1/MODY6 and Islet(Isl)-1/MODY7. |
| 620 | 11307309 | Mutations in HNF-1 alpha/MODY3 are the most common cause of MODY in Japanese identified to date accounting for about 15% of cases of MODY. |
| 621 | 11307309 | Mutations in the HNF-4 alpha/MODY1, glucokinase/MODY2, HNF-1 beta/MODY5 and Isl-1/MODY7 genes have also been found in Japanese; however, they are rare causes of MODY. |
| 622 | 11307309 | Patients who have mutations in the HNF-1 beta/MODY5 gene have non-diabetic kidney dysfunction including renal cysts. |
| 623 | 11307309 | Genetic approach for type 2 diabetes had done by using non-parameteric linkage analysis such as sibpair analysis which worked well and NIDDM1 and NIDDM2 have been identified to date. |
| 624 | 11307309 | The responsible gene for NIDDM1 was recently identified to be Calpain 10, and SNP43 in this gene could explain all of the evidence for linkage in Mexican American type 2 diabetes. |
| 625 | 11307309 | This form of diabetes can result from mutations in at least seven different genes: hepatocyte nuclear factor(HNF)-4 alpha/MODY1, glucokinase/MODY2, HNF-1 alpha/MODY3, insulin promoter factor(IPF-1)/MODY4, HNF-1 beta/MODY5, NeuroD1/MODY6 and Islet(Isl)-1/MODY7. |
| 626 | 11307309 | Mutations in HNF-1 alpha/MODY3 are the most common cause of MODY in Japanese identified to date accounting for about 15% of cases of MODY. |
| 627 | 11307309 | Mutations in the HNF-4 alpha/MODY1, glucokinase/MODY2, HNF-1 beta/MODY5 and Isl-1/MODY7 genes have also been found in Japanese; however, they are rare causes of MODY. |
| 628 | 11307309 | Patients who have mutations in the HNF-1 beta/MODY5 gene have non-diabetic kidney dysfunction including renal cysts. |
| 629 | 11307309 | Genetic approach for type 2 diabetes had done by using non-parameteric linkage analysis such as sibpair analysis which worked well and NIDDM1 and NIDDM2 have been identified to date. |
| 630 | 11307309 | The responsible gene for NIDDM1 was recently identified to be Calpain 10, and SNP43 in this gene could explain all of the evidence for linkage in Mexican American type 2 diabetes. |
| 631 | 11307309 | This form of diabetes can result from mutations in at least seven different genes: hepatocyte nuclear factor(HNF)-4 alpha/MODY1, glucokinase/MODY2, HNF-1 alpha/MODY3, insulin promoter factor(IPF-1)/MODY4, HNF-1 beta/MODY5, NeuroD1/MODY6 and Islet(Isl)-1/MODY7. |
| 632 | 11307309 | Mutations in HNF-1 alpha/MODY3 are the most common cause of MODY in Japanese identified to date accounting for about 15% of cases of MODY. |
| 633 | 11307309 | Mutations in the HNF-4 alpha/MODY1, glucokinase/MODY2, HNF-1 beta/MODY5 and Isl-1/MODY7 genes have also been found in Japanese; however, they are rare causes of MODY. |
| 634 | 11307309 | Patients who have mutations in the HNF-1 beta/MODY5 gene have non-diabetic kidney dysfunction including renal cysts. |
| 635 | 11307309 | Genetic approach for type 2 diabetes had done by using non-parameteric linkage analysis such as sibpair analysis which worked well and NIDDM1 and NIDDM2 have been identified to date. |
| 636 | 11307309 | The responsible gene for NIDDM1 was recently identified to be Calpain 10, and SNP43 in this gene could explain all of the evidence for linkage in Mexican American type 2 diabetes. |
| 637 | 11323086 | Heterozygous mutations in the genes encoding transcription factors (HNF-1alpha, HNF-1beta and HNF-4alpha) in the hepatocyte nuclear factor (HNF) network are associated with maturity-onset diabetes of the young (MODY). |
| 638 | 11323086 | We screened HNF-6 gene for mutations in 34 Japanese subjects with MODY/early-onset diabetes mellitus and 56 subjects with late-onset diabetes mellitus. |
| 639 | 11323086 | Heterozygous mutations in the genes encoding transcription factors (HNF-1alpha, HNF-1beta and HNF-4alpha) in the hepatocyte nuclear factor (HNF) network are associated with maturity-onset diabetes of the young (MODY). |
| 640 | 11323086 | We screened HNF-6 gene for mutations in 34 Japanese subjects with MODY/early-onset diabetes mellitus and 56 subjects with late-onset diabetes mellitus. |
| 641 | 11355750 | Searching for a novel MODY gene in this population, we investigated a candidate for encoding the forkhead transcription factor HNF-3alpha, which also belongs to the HNF-transcription cascade. |
| 642 | 11355750 | However, their frequencies were not significantly different between MODY and control subjects, indicating that mutations in the HNF-3alpha gene are not a major cause of MODY in Japanese patients. |
| 643 | 11355750 | Searching for a novel MODY gene in this population, we investigated a candidate for encoding the forkhead transcription factor HNF-3alpha, which also belongs to the HNF-transcription cascade. |
| 644 | 11355750 | However, their frequencies were not significantly different between MODY and control subjects, indicating that mutations in the HNF-3alpha gene are not a major cause of MODY in Japanese patients. |
| 645 | 11423471 | Mutations in the HNF4alpha gene are responsible for type 1 maturity-onset diabetes of the young (MODY1), which is characterized by a defect in insulin secretion. |
| 646 | 11423471 | Recent evidence has implicated AMP-activated protein kinase (AMPK) in the modulation of both insulin secretion by pancreatic beta-cells and the control of glucose-dependent gene expression in both hepatocytes and beta-cells. |
| 647 | 11423471 | Therefore, the question could be raised as to whether AMPK plays a role in these processes by modulating HNF-4alpha function. |
| 648 | 11423471 | In this study, we show that activation of AMPK by 5-amino-4-imidazolecarboxamide riboside (AICAR) in hepatocytes greatly diminished HNF-4alpha protein levels and consequently downregulates the expression of HNF-4alpha target genes. |
| 649 | 11423471 | Quantitative evaluation of HNF-4alpha target gene expression revealed diminished mRNA levels for HNF-1alpha, GLUT2, L-type pyruvate kinase, aldolase B, apolipoprotein (apo)-B, and apoCIII. |
| 650 | 11423471 | Our data clearly demonstrate that the MODY1/HNF-4alpha transcription factor is a novel target of AMPK in hepatocytes. |
| 651 | 11423471 | Accordingly, it can be suggested that in pancreatic beta-cells, AMPK also acts by decreasing HNF-4alpha protein level, and therefore insulin secretion. |
| 652 | 11423471 | Mutations in the HNF4alpha gene are responsible for type 1 maturity-onset diabetes of the young (MODY1), which is characterized by a defect in insulin secretion. |
| 653 | 11423471 | Recent evidence has implicated AMP-activated protein kinase (AMPK) in the modulation of both insulin secretion by pancreatic beta-cells and the control of glucose-dependent gene expression in both hepatocytes and beta-cells. |
| 654 | 11423471 | Therefore, the question could be raised as to whether AMPK plays a role in these processes by modulating HNF-4alpha function. |
| 655 | 11423471 | In this study, we show that activation of AMPK by 5-amino-4-imidazolecarboxamide riboside (AICAR) in hepatocytes greatly diminished HNF-4alpha protein levels and consequently downregulates the expression of HNF-4alpha target genes. |
| 656 | 11423471 | Quantitative evaluation of HNF-4alpha target gene expression revealed diminished mRNA levels for HNF-1alpha, GLUT2, L-type pyruvate kinase, aldolase B, apolipoprotein (apo)-B, and apoCIII. |
| 657 | 11423471 | Our data clearly demonstrate that the MODY1/HNF-4alpha transcription factor is a novel target of AMPK in hepatocytes. |
| 658 | 11423471 | Accordingly, it can be suggested that in pancreatic beta-cells, AMPK also acts by decreasing HNF-4alpha protein level, and therefore insulin secretion. |
| 659 | 11423471 | Mutations in the HNF4alpha gene are responsible for type 1 maturity-onset diabetes of the young (MODY1), which is characterized by a defect in insulin secretion. |
| 660 | 11423471 | Recent evidence has implicated AMP-activated protein kinase (AMPK) in the modulation of both insulin secretion by pancreatic beta-cells and the control of glucose-dependent gene expression in both hepatocytes and beta-cells. |
| 661 | 11423471 | Therefore, the question could be raised as to whether AMPK plays a role in these processes by modulating HNF-4alpha function. |
| 662 | 11423471 | In this study, we show that activation of AMPK by 5-amino-4-imidazolecarboxamide riboside (AICAR) in hepatocytes greatly diminished HNF-4alpha protein levels and consequently downregulates the expression of HNF-4alpha target genes. |
| 663 | 11423471 | Quantitative evaluation of HNF-4alpha target gene expression revealed diminished mRNA levels for HNF-1alpha, GLUT2, L-type pyruvate kinase, aldolase B, apolipoprotein (apo)-B, and apoCIII. |
| 664 | 11423471 | Our data clearly demonstrate that the MODY1/HNF-4alpha transcription factor is a novel target of AMPK in hepatocytes. |
| 665 | 11423471 | Accordingly, it can be suggested that in pancreatic beta-cells, AMPK also acts by decreasing HNF-4alpha protein level, and therefore insulin secretion. |
| 666 | 11423471 | Mutations in the HNF4alpha gene are responsible for type 1 maturity-onset diabetes of the young (MODY1), which is characterized by a defect in insulin secretion. |
| 667 | 11423471 | Recent evidence has implicated AMP-activated protein kinase (AMPK) in the modulation of both insulin secretion by pancreatic beta-cells and the control of glucose-dependent gene expression in both hepatocytes and beta-cells. |
| 668 | 11423471 | Therefore, the question could be raised as to whether AMPK plays a role in these processes by modulating HNF-4alpha function. |
| 669 | 11423471 | In this study, we show that activation of AMPK by 5-amino-4-imidazolecarboxamide riboside (AICAR) in hepatocytes greatly diminished HNF-4alpha protein levels and consequently downregulates the expression of HNF-4alpha target genes. |
| 670 | 11423471 | Quantitative evaluation of HNF-4alpha target gene expression revealed diminished mRNA levels for HNF-1alpha, GLUT2, L-type pyruvate kinase, aldolase B, apolipoprotein (apo)-B, and apoCIII. |
| 671 | 11423471 | Our data clearly demonstrate that the MODY1/HNF-4alpha transcription factor is a novel target of AMPK in hepatocytes. |
| 672 | 11423471 | Accordingly, it can be suggested that in pancreatic beta-cells, AMPK also acts by decreasing HNF-4alpha protein level, and therefore insulin secretion. |
| 673 | 11423471 | Mutations in the HNF4alpha gene are responsible for type 1 maturity-onset diabetes of the young (MODY1), which is characterized by a defect in insulin secretion. |
| 674 | 11423471 | Recent evidence has implicated AMP-activated protein kinase (AMPK) in the modulation of both insulin secretion by pancreatic beta-cells and the control of glucose-dependent gene expression in both hepatocytes and beta-cells. |
| 675 | 11423471 | Therefore, the question could be raised as to whether AMPK plays a role in these processes by modulating HNF-4alpha function. |
| 676 | 11423471 | In this study, we show that activation of AMPK by 5-amino-4-imidazolecarboxamide riboside (AICAR) in hepatocytes greatly diminished HNF-4alpha protein levels and consequently downregulates the expression of HNF-4alpha target genes. |
| 677 | 11423471 | Quantitative evaluation of HNF-4alpha target gene expression revealed diminished mRNA levels for HNF-1alpha, GLUT2, L-type pyruvate kinase, aldolase B, apolipoprotein (apo)-B, and apoCIII. |
| 678 | 11423471 | Our data clearly demonstrate that the MODY1/HNF-4alpha transcription factor is a novel target of AMPK in hepatocytes. |
| 679 | 11423471 | Accordingly, it can be suggested that in pancreatic beta-cells, AMPK also acts by decreasing HNF-4alpha protein level, and therefore insulin secretion. |
| 680 | 11423471 | Mutations in the HNF4alpha gene are responsible for type 1 maturity-onset diabetes of the young (MODY1), which is characterized by a defect in insulin secretion. |
| 681 | 11423471 | Recent evidence has implicated AMP-activated protein kinase (AMPK) in the modulation of both insulin secretion by pancreatic beta-cells and the control of glucose-dependent gene expression in both hepatocytes and beta-cells. |
| 682 | 11423471 | Therefore, the question could be raised as to whether AMPK plays a role in these processes by modulating HNF-4alpha function. |
| 683 | 11423471 | In this study, we show that activation of AMPK by 5-amino-4-imidazolecarboxamide riboside (AICAR) in hepatocytes greatly diminished HNF-4alpha protein levels and consequently downregulates the expression of HNF-4alpha target genes. |
| 684 | 11423471 | Quantitative evaluation of HNF-4alpha target gene expression revealed diminished mRNA levels for HNF-1alpha, GLUT2, L-type pyruvate kinase, aldolase B, apolipoprotein (apo)-B, and apoCIII. |
| 685 | 11423471 | Our data clearly demonstrate that the MODY1/HNF-4alpha transcription factor is a novel target of AMPK in hepatocytes. |
| 686 | 11423471 | Accordingly, it can be suggested that in pancreatic beta-cells, AMPK also acts by decreasing HNF-4alpha protein level, and therefore insulin secretion. |
| 687 | 11435618 | We show here that loss of HNF4alpha function by both mutations is increased through impaired physical interaction and functional cooperation between HNF4alpha and p300. |
| 688 | 11440371 | Routine mutation screening of HNF-1alpha and GCK genes in MODY diagnosis: how effective are the techniques of DHPLC and direct sequencing used in combination? |
| 689 | 11463573 | Mutations in the human genes encoding the tissue-specific transcription factors hepatocyte nuclear factor (HNF)1alpha, HNF1beta and HNF4alpha are responsible for maturity onset diabetes of the young (MODY), a monogenic dominant inherited form of diabetes mellitus characterized by defective insulin secretion of the pancreatic beta-cells. |
| 690 | 11485019 | Furthermore, in the human beta cell GLUT1 mRNA is predominant when compared to GLUT2 and glucose influx appears to be largely mediated by this low-Km transporter. |
| 691 | 11485019 | Thus, we looked for the presence of sequence variants by polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) within the GLUT1 gene in 90 Italian pedigrees negative at the search for mutations in glucokinase (MODY2) and hepatocyte nuclear factor-1alpha (MODY3), the two genes responsible for about 60% of MODY cases in Italian children. |
| 692 | 11485019 | In conclusion, it appears from these results that the glucose transporter gene GLUT1 is unlikely to play a major role in the etiology of MODY diabetes. |
| 693 | 11485019 | Furthermore, in the human beta cell GLUT1 mRNA is predominant when compared to GLUT2 and glucose influx appears to be largely mediated by this low-Km transporter. |
| 694 | 11485019 | Thus, we looked for the presence of sequence variants by polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) within the GLUT1 gene in 90 Italian pedigrees negative at the search for mutations in glucokinase (MODY2) and hepatocyte nuclear factor-1alpha (MODY3), the two genes responsible for about 60% of MODY cases in Italian children. |
| 695 | 11485019 | In conclusion, it appears from these results that the glucose transporter gene GLUT1 is unlikely to play a major role in the etiology of MODY diabetes. |
| 696 | 11554773 | Diabetes is caused either by mutations in the glucokinase gene (glucokinase MODY) or by mutations in transcription factors (transcription factor MODY). |
| 697 | 11554773 | Transcription factor maturity-onset diabetes of the young, caused by mutations in the hepatocyte nuclear factor genes HNF-1alpha, HNF-4alpha and HNF-1beta, and in insulin promoter factor-1 results in a progressive beta-cell defect with increasing treatment requirements and diabetic complications. |
| 698 | 11554773 | Diabetes is caused either by mutations in the glucokinase gene (glucokinase MODY) or by mutations in transcription factors (transcription factor MODY). |
| 699 | 11554773 | Transcription factor maturity-onset diabetes of the young, caused by mutations in the hepatocyte nuclear factor genes HNF-1alpha, HNF-4alpha and HNF-1beta, and in insulin promoter factor-1 results in a progressive beta-cell defect with increasing treatment requirements and diabetic complications. |
| 700 | 11557972 | Here we show that the transcriptional coactivator PGC-1 is strongly induced in liver in fasting mice and in three mouse models of insulin action deficiency: streptozotocin-induced diabetes, ob/ob genotype and liver insulin-receptor knockout. |
| 701 | 11557972 | Adenoviral-mediated expression of PGC-1 in hepatocytes in culture or in vivo strongly activates an entire programme of key gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, leading to increased glucose output. |
| 702 | 11557972 | Full transcriptional activation of the PEPCK promoter requires coactivation of the glucocorticoid receptor and the liver-enriched transcription factor HNF-4alpha (hepatic nuclear factor-4alpha) by PGC-1. |
| 703 | 11557972 | These results implicate PGC-1 as a key modulator of hepatic gluconeogenesis and as a central target of the insulin-cAMP axis in liver. |
| 704 | 11590126 | Maturity-onset diabetes of the young (MODY) is a monogenic, autosomal dominant subtype of early-onset diabetes mellitus due to defective insulin secretion by the pancreatic beta-cell in humans. |
| 705 | 11590126 | HNF-4alpha (MODY1), HNF-1alpha (MODY3), IPF-1 (also known as PDX-1, MODY4) and HNF-1beta (MODY5). |
| 706 | 11590126 | Transfection assays with various deletions and mutants of the P2 promoter reveal functional binding sites for HNF-1alpha, HNF-1beta and IPF-1, the other transcription factors known to encode MODY genes. |
| 707 | 11590126 | We demonstrate the significance of this alternative promoter in a large MODY family where a mutated IPF-1 binding site in the P2 promoter of the HNF-4alpha gene co-segregates with diabetes (LOD score 3.25). |
| 708 | 11590126 | Maturity-onset diabetes of the young (MODY) is a monogenic, autosomal dominant subtype of early-onset diabetes mellitus due to defective insulin secretion by the pancreatic beta-cell in humans. |
| 709 | 11590126 | HNF-4alpha (MODY1), HNF-1alpha (MODY3), IPF-1 (also known as PDX-1, MODY4) and HNF-1beta (MODY5). |
| 710 | 11590126 | Transfection assays with various deletions and mutants of the P2 promoter reveal functional binding sites for HNF-1alpha, HNF-1beta and IPF-1, the other transcription factors known to encode MODY genes. |
| 711 | 11590126 | We demonstrate the significance of this alternative promoter in a large MODY family where a mutated IPF-1 binding site in the P2 promoter of the HNF-4alpha gene co-segregates with diabetes (LOD score 3.25). |
| 712 | 11590126 | Maturity-onset diabetes of the young (MODY) is a monogenic, autosomal dominant subtype of early-onset diabetes mellitus due to defective insulin secretion by the pancreatic beta-cell in humans. |
| 713 | 11590126 | HNF-4alpha (MODY1), HNF-1alpha (MODY3), IPF-1 (also known as PDX-1, MODY4) and HNF-1beta (MODY5). |
| 714 | 11590126 | Transfection assays with various deletions and mutants of the P2 promoter reveal functional binding sites for HNF-1alpha, HNF-1beta and IPF-1, the other transcription factors known to encode MODY genes. |
| 715 | 11590126 | We demonstrate the significance of this alternative promoter in a large MODY family where a mutated IPF-1 binding site in the P2 promoter of the HNF-4alpha gene co-segregates with diabetes (LOD score 3.25). |
| 716 | 11590126 | Maturity-onset diabetes of the young (MODY) is a monogenic, autosomal dominant subtype of early-onset diabetes mellitus due to defective insulin secretion by the pancreatic beta-cell in humans. |
| 717 | 11590126 | HNF-4alpha (MODY1), HNF-1alpha (MODY3), IPF-1 (also known as PDX-1, MODY4) and HNF-1beta (MODY5). |
| 718 | 11590126 | Transfection assays with various deletions and mutants of the P2 promoter reveal functional binding sites for HNF-1alpha, HNF-1beta and IPF-1, the other transcription factors known to encode MODY genes. |
| 719 | 11590126 | We demonstrate the significance of this alternative promoter in a large MODY family where a mutated IPF-1 binding site in the P2 promoter of the HNF-4alpha gene co-segregates with diabetes (LOD score 3.25). |
| 720 | 11668623 | Studies of the variability of the hepatocyte nuclear factor-1beta (HNF-1beta / TCF2) and the dimerization cofactor of HNF-1 (DcoH / PCBD) genes in relation to type 2 diabetes mellitus and beta-cell function. |
| 721 | 11668623 | To investigate whether mutations in HNF-1 are implicated in the pathogenesis of MODY or late-onset diabetes with and without nephropathy in Danish Caucasians we examined the HNF-1beta (TCF2) and the dimerization cofactor of HNF-1 (DCoH, PCBD) genes for mutations in 11 MODY probands, 28 type 2 diabetic patients with nephropathy, and 46 type 2 diabetic patients with an impaired beta-cell function by combined single-strand conformation polymorphism (SSCP) and heteroduplex analysis. |
| 722 | 11668623 | In conclusion, mutations in HNF-1beta and DCoH are not a major cause of MODY or late onset type 2 diabetes in Danish Caucasian subjects. |
| 723 | 11668623 | Studies of the variability of the hepatocyte nuclear factor-1beta (HNF-1beta / TCF2) and the dimerization cofactor of HNF-1 (DcoH / PCBD) genes in relation to type 2 diabetes mellitus and beta-cell function. |
| 724 | 11668623 | To investigate whether mutations in HNF-1 are implicated in the pathogenesis of MODY or late-onset diabetes with and without nephropathy in Danish Caucasians we examined the HNF-1beta (TCF2) and the dimerization cofactor of HNF-1 (DCoH, PCBD) genes for mutations in 11 MODY probands, 28 type 2 diabetic patients with nephropathy, and 46 type 2 diabetic patients with an impaired beta-cell function by combined single-strand conformation polymorphism (SSCP) and heteroduplex analysis. |
| 725 | 11668623 | In conclusion, mutations in HNF-1beta and DCoH are not a major cause of MODY or late onset type 2 diabetes in Danish Caucasian subjects. |
| 726 | 11679424 | We found decreased steady-state mRNA levels of genes encoding glucose transporter 2 (Glut2), neutral and basic amino acid transporter, liver pyruvate kinase (L-Pk), and insulin in Hnf-1alpha(-/-) mice. |
| 727 | 11679424 | In addition, we determined that the expression of several islet-enriched transcription factors, including Pdx-1, Hnf-4alpha, and Neuro-D1/Beta-2, was reduced in Hnf-1alpha(-/-) mice. |
| 728 | 11679424 | This expression profile was pancreatic islet-specific and distinct from hepatocytes, where we found normal expression of Glut2, L-Pk, and Hnf-4alpha in the liver of Hnf-1alpha(-/-) mice. |
| 729 | 11679424 | The expression of small heterodimer partner (Shp-1), an orphan receptor that can heterodimerize with Hnf-4alpha and inhibit its transcriptional activity, was also reduced in Hnf-1alpha(-/-) islets. |
| 730 | 11679424 | We characterized a 0.58-kb Shp-1 promoter and determined that the decreased expression of Shp-1 may be indirectly mediated by a downregulation of Hnf-4alpha. |
| 731 | 11679424 | We further showed that Shp-1 can repress its own transcriptional activation by inhibiting Hnf-4alpha function, thereby establishing a feedback autoregulatory loop. |
| 732 | 11679424 | We found decreased steady-state mRNA levels of genes encoding glucose transporter 2 (Glut2), neutral and basic amino acid transporter, liver pyruvate kinase (L-Pk), and insulin in Hnf-1alpha(-/-) mice. |
| 733 | 11679424 | In addition, we determined that the expression of several islet-enriched transcription factors, including Pdx-1, Hnf-4alpha, and Neuro-D1/Beta-2, was reduced in Hnf-1alpha(-/-) mice. |
| 734 | 11679424 | This expression profile was pancreatic islet-specific and distinct from hepatocytes, where we found normal expression of Glut2, L-Pk, and Hnf-4alpha in the liver of Hnf-1alpha(-/-) mice. |
| 735 | 11679424 | The expression of small heterodimer partner (Shp-1), an orphan receptor that can heterodimerize with Hnf-4alpha and inhibit its transcriptional activity, was also reduced in Hnf-1alpha(-/-) islets. |
| 736 | 11679424 | We characterized a 0.58-kb Shp-1 promoter and determined that the decreased expression of Shp-1 may be indirectly mediated by a downregulation of Hnf-4alpha. |
| 737 | 11679424 | We further showed that Shp-1 can repress its own transcriptional activation by inhibiting Hnf-4alpha function, thereby establishing a feedback autoregulatory loop. |
| 738 | 11679424 | We found decreased steady-state mRNA levels of genes encoding glucose transporter 2 (Glut2), neutral and basic amino acid transporter, liver pyruvate kinase (L-Pk), and insulin in Hnf-1alpha(-/-) mice. |
| 739 | 11679424 | In addition, we determined that the expression of several islet-enriched transcription factors, including Pdx-1, Hnf-4alpha, and Neuro-D1/Beta-2, was reduced in Hnf-1alpha(-/-) mice. |
| 740 | 11679424 | This expression profile was pancreatic islet-specific and distinct from hepatocytes, where we found normal expression of Glut2, L-Pk, and Hnf-4alpha in the liver of Hnf-1alpha(-/-) mice. |
| 741 | 11679424 | The expression of small heterodimer partner (Shp-1), an orphan receptor that can heterodimerize with Hnf-4alpha and inhibit its transcriptional activity, was also reduced in Hnf-1alpha(-/-) islets. |
| 742 | 11679424 | We characterized a 0.58-kb Shp-1 promoter and determined that the decreased expression of Shp-1 may be indirectly mediated by a downregulation of Hnf-4alpha. |
| 743 | 11679424 | We further showed that Shp-1 can repress its own transcriptional activation by inhibiting Hnf-4alpha function, thereby establishing a feedback autoregulatory loop. |
| 744 | 11679424 | We found decreased steady-state mRNA levels of genes encoding glucose transporter 2 (Glut2), neutral and basic amino acid transporter, liver pyruvate kinase (L-Pk), and insulin in Hnf-1alpha(-/-) mice. |
| 745 | 11679424 | In addition, we determined that the expression of several islet-enriched transcription factors, including Pdx-1, Hnf-4alpha, and Neuro-D1/Beta-2, was reduced in Hnf-1alpha(-/-) mice. |
| 746 | 11679424 | This expression profile was pancreatic islet-specific and distinct from hepatocytes, where we found normal expression of Glut2, L-Pk, and Hnf-4alpha in the liver of Hnf-1alpha(-/-) mice. |
| 747 | 11679424 | The expression of small heterodimer partner (Shp-1), an orphan receptor that can heterodimerize with Hnf-4alpha and inhibit its transcriptional activity, was also reduced in Hnf-1alpha(-/-) islets. |
| 748 | 11679424 | We characterized a 0.58-kb Shp-1 promoter and determined that the decreased expression of Shp-1 may be indirectly mediated by a downregulation of Hnf-4alpha. |
| 749 | 11679424 | We further showed that Shp-1 can repress its own transcriptional activation by inhibiting Hnf-4alpha function, thereby establishing a feedback autoregulatory loop. |
| 750 | 11679424 | We found decreased steady-state mRNA levels of genes encoding glucose transporter 2 (Glut2), neutral and basic amino acid transporter, liver pyruvate kinase (L-Pk), and insulin in Hnf-1alpha(-/-) mice. |
| 751 | 11679424 | In addition, we determined that the expression of several islet-enriched transcription factors, including Pdx-1, Hnf-4alpha, and Neuro-D1/Beta-2, was reduced in Hnf-1alpha(-/-) mice. |
| 752 | 11679424 | This expression profile was pancreatic islet-specific and distinct from hepatocytes, where we found normal expression of Glut2, L-Pk, and Hnf-4alpha in the liver of Hnf-1alpha(-/-) mice. |
| 753 | 11679424 | The expression of small heterodimer partner (Shp-1), an orphan receptor that can heterodimerize with Hnf-4alpha and inhibit its transcriptional activity, was also reduced in Hnf-1alpha(-/-) islets. |
| 754 | 11679424 | We characterized a 0.58-kb Shp-1 promoter and determined that the decreased expression of Shp-1 may be indirectly mediated by a downregulation of Hnf-4alpha. |
| 755 | 11679424 | We further showed that Shp-1 can repress its own transcriptional activation by inhibiting Hnf-4alpha function, thereby establishing a feedback autoregulatory loop. |
| 756 | 11716293 | Mutations in the hepatocyte nuclear factor-1beta (HNF-1beta) gene have been shown to be a cause of maturity-onset diabetes of the young (MODY). |
| 757 | 11717395 | Mutations in the human genes encoding hepatocyte nuclear factors (HNF) 1alpha, 1beta, 4alpha, and IPF1(PDX1/IDX1/STF1) result in pancreatic beta cell dysfunction and diabetes mellitus. |
| 758 | 11717395 | Hnf1alpha also exerts direct control of pancreatic-specific expression of hnf4gamma and hnf3gamma. |
| 759 | 11717395 | Hnf1alpha dependence of hnf4alpha, hnf4gamma, hnf3gamma, and two previously characterized distal targets (glut2 and pklr) is established only after differentiated cells arise during pancreatic embryonic development. |
| 760 | 11806470 | The aim of our study was to determine the contribution of the HNF-1alpha gene to the development of MODY in a Polish population. |
| 761 | 11806470 | In conclusion, we have identified a new HNF-1alpha variant that represents the first MODY mutation described in a Polish population. |
| 762 | 11806470 | MODY3 mutations, including those in the exon 4 "hot spot", do not appear to be a very common cause of MODY in the Polish population. |
| 763 | 11806470 | The aim of our study was to determine the contribution of the HNF-1alpha gene to the development of MODY in a Polish population. |
| 764 | 11806470 | In conclusion, we have identified a new HNF-1alpha variant that represents the first MODY mutation described in a Polish population. |
| 765 | 11806470 | MODY3 mutations, including those in the exon 4 "hot spot", do not appear to be a very common cause of MODY in the Polish population. |
| 766 | 11806470 | The aim of our study was to determine the contribution of the HNF-1alpha gene to the development of MODY in a Polish population. |
| 767 | 11806470 | In conclusion, we have identified a new HNF-1alpha variant that represents the first MODY mutation described in a Polish population. |
| 768 | 11806470 | MODY3 mutations, including those in the exon 4 "hot spot", do not appear to be a very common cause of MODY in the Polish population. |
| 769 | 11827432 | To determine the prevalence of MODY and early-onset type 2 diabetes with the mutation of HNF-1alpha gene in Korea, we analyzed this gene in 69 Korean early-onset type 2 diabetics and in 35 healthy persons using the single-strand conformation polymorphism (SSCP) technique and direct sequencing. |
| 770 | 11827432 | We concluded that this genetic mutation in HNF-1alpha gene may not be a common contributor to MODY and early-onset type 2 diabetes susceptibility in Korea. |
| 771 | 11827432 | To determine the prevalence of MODY and early-onset type 2 diabetes with the mutation of HNF-1alpha gene in Korea, we analyzed this gene in 69 Korean early-onset type 2 diabetics and in 35 healthy persons using the single-strand conformation polymorphism (SSCP) technique and direct sequencing. |
| 772 | 11827432 | We concluded that this genetic mutation in HNF-1alpha gene may not be a common contributor to MODY and early-onset type 2 diabetes susceptibility in Korea. |
| 773 | 11890664 | Nuclear translocation of SHP and visualization of interaction with HNF-4alpha in living cells. |
| 774 | 11890664 | Mutations in small heterodimer partner (SHP) and hepatocyte nuclear factor 4alpha (HNF4alpha) are associated with mild obesity and diabetes mellitus, respectively. |
| 775 | 11890664 | Expressed SHP resided only in the cytoplasm in COS-7 cells which lacks HNF4alpha, but predominantly in the nucleus in insulinoma cells (MIN6). |
| 776 | 11890664 | We found fluorescence resonance energy transfer between GFP-tagged SHP and HNF4alpha, indicating a specific close association between them in the nucleus. |
| 777 | 11890664 | The results strongly suggest that SHP exists primarily in the cytoplasm and is translocated into the nucleus on interacting with its nuclear receptor partner HNF4alpha. |
| 778 | 11890664 | Nuclear translocation of SHP and visualization of interaction with HNF-4alpha in living cells. |
| 779 | 11890664 | Mutations in small heterodimer partner (SHP) and hepatocyte nuclear factor 4alpha (HNF4alpha) are associated with mild obesity and diabetes mellitus, respectively. |
| 780 | 11890664 | Expressed SHP resided only in the cytoplasm in COS-7 cells which lacks HNF4alpha, but predominantly in the nucleus in insulinoma cells (MIN6). |
| 781 | 11890664 | We found fluorescence resonance energy transfer between GFP-tagged SHP and HNF4alpha, indicating a specific close association between them in the nucleus. |
| 782 | 11890664 | The results strongly suggest that SHP exists primarily in the cytoplasm and is translocated into the nucleus on interacting with its nuclear receptor partner HNF4alpha. |
| 783 | 11890664 | Nuclear translocation of SHP and visualization of interaction with HNF-4alpha in living cells. |
| 784 | 11890664 | Mutations in small heterodimer partner (SHP) and hepatocyte nuclear factor 4alpha (HNF4alpha) are associated with mild obesity and diabetes mellitus, respectively. |
| 785 | 11890664 | Expressed SHP resided only in the cytoplasm in COS-7 cells which lacks HNF4alpha, but predominantly in the nucleus in insulinoma cells (MIN6). |
| 786 | 11890664 | We found fluorescence resonance energy transfer between GFP-tagged SHP and HNF4alpha, indicating a specific close association between them in the nucleus. |
| 787 | 11890664 | The results strongly suggest that SHP exists primarily in the cytoplasm and is translocated into the nucleus on interacting with its nuclear receptor partner HNF4alpha. |
| 788 | 11890664 | Nuclear translocation of SHP and visualization of interaction with HNF-4alpha in living cells. |
| 789 | 11890664 | Mutations in small heterodimer partner (SHP) and hepatocyte nuclear factor 4alpha (HNF4alpha) are associated with mild obesity and diabetes mellitus, respectively. |
| 790 | 11890664 | Expressed SHP resided only in the cytoplasm in COS-7 cells which lacks HNF4alpha, but predominantly in the nucleus in insulinoma cells (MIN6). |
| 791 | 11890664 | We found fluorescence resonance energy transfer between GFP-tagged SHP and HNF4alpha, indicating a specific close association between them in the nucleus. |
| 792 | 11890664 | The results strongly suggest that SHP exists primarily in the cytoplasm and is translocated into the nucleus on interacting with its nuclear receptor partner HNF4alpha. |
| 793 | 11890664 | Nuclear translocation of SHP and visualization of interaction with HNF-4alpha in living cells. |
| 794 | 11890664 | Mutations in small heterodimer partner (SHP) and hepatocyte nuclear factor 4alpha (HNF4alpha) are associated with mild obesity and diabetes mellitus, respectively. |
| 795 | 11890664 | Expressed SHP resided only in the cytoplasm in COS-7 cells which lacks HNF4alpha, but predominantly in the nucleus in insulinoma cells (MIN6). |
| 796 | 11890664 | We found fluorescence resonance energy transfer between GFP-tagged SHP and HNF4alpha, indicating a specific close association between them in the nucleus. |
| 797 | 11890664 | The results strongly suggest that SHP exists primarily in the cytoplasm and is translocated into the nucleus on interacting with its nuclear receptor partner HNF4alpha. |
| 798 | 11904435 | Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. |
| 799 | 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. |
| 800 | 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(+/-). |
| 801 | 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(+/-)). |
| 802 | 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. |
| 803 | 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. |
| 804 | 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. |
| 805 | 11904435 | Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. |
| 806 | 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. |
| 807 | 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(+/-). |
| 808 | 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(+/-)). |
| 809 | 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. |
| 810 | 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. |
| 811 | 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. |
| 812 | 11916906 | Mutations of the hepatocyte nuclear factor-4alpha (HNF-4alpha) gene are associated with a subtype of maturity-onset diabetes of the young (MODY1) that is characterized by impaired insulin secretion in response to a glucose load. |
| 813 | 11916906 | In the present study, we showed, using a yeast two-hybrid screening assay, that thyroid hormone receptor interacting protein 3 (Trip3) interacted with HNF-4alpha, and their interaction was confirmed by the glutathione S-transferase pull-down assay. |
| 814 | 11916906 | Cotransfection experiments indicated that Trip3 could enhance (two- to threefold) the transcription activity of HNF-4alpha in COS-7 cells and MIN6 cells. |
| 815 | 11916906 | These results suggest that Trip3 is a coactivator of HNF-4alpha. |
| 816 | 11916906 | Mutation screening revealed that variation of the Trip3 gene is not a common cause of MODY/early-onset type 2 diabetes in Japanese individuals. |
| 817 | 11916906 | Trip3 may play an important role in glucose metabolism by regulating the transcription activity of HNF-4alpha. |
| 818 | 11916906 | Mutations of the hepatocyte nuclear factor-4alpha (HNF-4alpha) gene are associated with a subtype of maturity-onset diabetes of the young (MODY1) that is characterized by impaired insulin secretion in response to a glucose load. |
| 819 | 11916906 | In the present study, we showed, using a yeast two-hybrid screening assay, that thyroid hormone receptor interacting protein 3 (Trip3) interacted with HNF-4alpha, and their interaction was confirmed by the glutathione S-transferase pull-down assay. |
| 820 | 11916906 | Cotransfection experiments indicated that Trip3 could enhance (two- to threefold) the transcription activity of HNF-4alpha in COS-7 cells and MIN6 cells. |
| 821 | 11916906 | These results suggest that Trip3 is a coactivator of HNF-4alpha. |
| 822 | 11916906 | Mutation screening revealed that variation of the Trip3 gene is not a common cause of MODY/early-onset type 2 diabetes in Japanese individuals. |
| 823 | 11916906 | Trip3 may play an important role in glucose metabolism by regulating the transcription activity of HNF-4alpha. |
| 824 | 11916906 | Mutations of the hepatocyte nuclear factor-4alpha (HNF-4alpha) gene are associated with a subtype of maturity-onset diabetes of the young (MODY1) that is characterized by impaired insulin secretion in response to a glucose load. |
| 825 | 11916906 | In the present study, we showed, using a yeast two-hybrid screening assay, that thyroid hormone receptor interacting protein 3 (Trip3) interacted with HNF-4alpha, and their interaction was confirmed by the glutathione S-transferase pull-down assay. |
| 826 | 11916906 | Cotransfection experiments indicated that Trip3 could enhance (two- to threefold) the transcription activity of HNF-4alpha in COS-7 cells and MIN6 cells. |
| 827 | 11916906 | These results suggest that Trip3 is a coactivator of HNF-4alpha. |
| 828 | 11916906 | Mutation screening revealed that variation of the Trip3 gene is not a common cause of MODY/early-onset type 2 diabetes in Japanese individuals. |
| 829 | 11916906 | Trip3 may play an important role in glucose metabolism by regulating the transcription activity of HNF-4alpha. |
| 830 | 11916906 | Mutations of the hepatocyte nuclear factor-4alpha (HNF-4alpha) gene are associated with a subtype of maturity-onset diabetes of the young (MODY1) that is characterized by impaired insulin secretion in response to a glucose load. |
| 831 | 11916906 | In the present study, we showed, using a yeast two-hybrid screening assay, that thyroid hormone receptor interacting protein 3 (Trip3) interacted with HNF-4alpha, and their interaction was confirmed by the glutathione S-transferase pull-down assay. |
| 832 | 11916906 | Cotransfection experiments indicated that Trip3 could enhance (two- to threefold) the transcription activity of HNF-4alpha in COS-7 cells and MIN6 cells. |
| 833 | 11916906 | These results suggest that Trip3 is a coactivator of HNF-4alpha. |
| 834 | 11916906 | Mutation screening revealed that variation of the Trip3 gene is not a common cause of MODY/early-onset type 2 diabetes in Japanese individuals. |
| 835 | 11916906 | Trip3 may play an important role in glucose metabolism by regulating the transcription activity of HNF-4alpha. |
| 836 | 11916906 | Mutations of the hepatocyte nuclear factor-4alpha (HNF-4alpha) gene are associated with a subtype of maturity-onset diabetes of the young (MODY1) that is characterized by impaired insulin secretion in response to a glucose load. |
| 837 | 11916906 | In the present study, we showed, using a yeast two-hybrid screening assay, that thyroid hormone receptor interacting protein 3 (Trip3) interacted with HNF-4alpha, and their interaction was confirmed by the glutathione S-transferase pull-down assay. |
| 838 | 11916906 | Cotransfection experiments indicated that Trip3 could enhance (two- to threefold) the transcription activity of HNF-4alpha in COS-7 cells and MIN6 cells. |
| 839 | 11916906 | These results suggest that Trip3 is a coactivator of HNF-4alpha. |
| 840 | 11916906 | Mutation screening revealed that variation of the Trip3 gene is not a common cause of MODY/early-onset type 2 diabetes in Japanese individuals. |
| 841 | 11916906 | Trip3 may play an important role in glucose metabolism by regulating the transcription activity of HNF-4alpha. |
| 842 | 11916906 | Mutations of the hepatocyte nuclear factor-4alpha (HNF-4alpha) gene are associated with a subtype of maturity-onset diabetes of the young (MODY1) that is characterized by impaired insulin secretion in response to a glucose load. |
| 843 | 11916906 | In the present study, we showed, using a yeast two-hybrid screening assay, that thyroid hormone receptor interacting protein 3 (Trip3) interacted with HNF-4alpha, and their interaction was confirmed by the glutathione S-transferase pull-down assay. |
| 844 | 11916906 | Cotransfection experiments indicated that Trip3 could enhance (two- to threefold) the transcription activity of HNF-4alpha in COS-7 cells and MIN6 cells. |
| 845 | 11916906 | These results suggest that Trip3 is a coactivator of HNF-4alpha. |
| 846 | 11916906 | Mutation screening revealed that variation of the Trip3 gene is not a common cause of MODY/early-onset type 2 diabetes in Japanese individuals. |
| 847 | 11916906 | Trip3 may play an important role in glucose metabolism by regulating the transcription activity of HNF-4alpha. |
| 848 | 11924926 | In humans, mutations in leptin, leptin receptor, proopiomelanocortin (POMC), melanocortin-4 receptor (MC4R) and prohormone convertase 1 (PC1) have been described in patients with severe obesity. |
| 849 | 11924926 | Most of these obesity disorders, with the exception of the MC4R mutations, exhibit recessive inheritance and a distinct phenotype with varying degrees of hypothalamic dysfunction, and they unravel the critical role of the central leptin and melanocortin pathways in human appetite control and energy homeostasis. |
| 850 | 11924926 | To date, six MODY genes have been identified, the glucokinase gene and five beta cell-specific transcription factor genes, hepatocyte nuclear factor-1alpha (HNF-1alpha), HNF-1beta, HNF-4alpha, insulin promoter factor-1 (IPF-1) and NeuroD1/BETA2. |
| 851 | 11924926 | At the other end of the spectrum are the inherited syndromes of insulin resistance that are caused by mutations in the insulin receptor gene and in the adipocyte-specific transcription factor PPARgamma. |
| 852 | 11978637 | Hepatocyte nuclear factor-1alpha recruits the transcriptional co-activator p300 on the GLUT2 gene promoter. |
| 853 | 11978637 | Mutations in the hepatocyte nuclear factor (HNF)-1alpha gene have been linked to subtype 3 of maturity-onset diabetes of the young (MODY), a disease characterized by a primary defect in insulin secretion. |
| 854 | 11978637 | Here we show that the human GLUT2 gene is closely regulated by HNF-1alpha via sequences downstream of the transcriptional start site by interaction with transcriptional co-activator p300. |
| 855 | 11978637 | These findings demonstrated that HNF-1alpha binds to the 5'-untranslated region of GLUT2 and that p300 acts as a transcriptional co-activator for HNF-1alpha. |
| 856 | 11978663 | After exclusion of three families with MODY1, MODY3, and mitochondrial mutations, the highest NPL scores were observed on chromosomes 1p (D1S438; NPL 2.6; P < 0.01), 3p (D3S1620; NPL 2.2; P < 0.03), 5q (D5S1465; NPL 2.1; P < 0.03), 7q (D7S820; NPL 2.0; P < 0.03), 18q (D18S535; NPL 1.9; P < 0.04), 20q (D20S195; NPL 2.5; P < 0.02), and 21q (D21S1446; NPL 2.2; P < 0.03). |
| 857 | 11978663 | We conclude that considerable heterogeneity exists in Scandinavian subjects with EOD; 24% had MODY or maternally inherited diabetes and deafness, and approximately 60% were GAD antibody positive or had type 1 diabetes-associated HLA genotypes. |
| 858 | 11978663 | After exclusion of three families with MODY1, MODY3, and mitochondrial mutations, the highest NPL scores were observed on chromosomes 1p (D1S438; NPL 2.6; P < 0.01), 3p (D3S1620; NPL 2.2; P < 0.03), 5q (D5S1465; NPL 2.1; P < 0.03), 7q (D7S820; NPL 2.0; P < 0.03), 18q (D18S535; NPL 1.9; P < 0.04), 20q (D20S195; NPL 2.5; P < 0.02), and 21q (D21S1446; NPL 2.2; P < 0.03). |
| 859 | 11978663 | We conclude that considerable heterogeneity exists in Scandinavian subjects with EOD; 24% had MODY or maternally inherited diabetes and deafness, and approximately 60% were GAD antibody positive or had type 1 diabetes-associated HLA genotypes. |
| 860 | 11979019 | Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of familial diabetes mellitus characterized by early onset, autosomal dominant inheritance and primary defects of insulin secretion. |
| 861 | 11979019 | These genes encode the enzyme glucokinase and the transcription factors hepatocyte nuclear factor 4alpha, hepatocyte nuclear factor 1alpha, insulin promoter factor-1, hepatocyte nuclear factor 1beta and neuroD1. |
| 862 | 11984998 | Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of type 2 diabetes characterised by an early onset, an autosomal dominant inheritance, and a primary defect in insulin secretion. |
| 863 | 11984998 | So far, six MODY genes have been identified (MODY1-6): hepatocyte nuclear factor (HNF-4 alpha), glucokinase, HNF-1 alpha, HNF-1 beta, insulin promoter factor 1(IPF-1), and neurogenic differentiation factor 1 (NEUROD1). |
| 864 | 11984998 | MODY2 and MODY3 are the most common forms of MODY. |
| 865 | 11984998 | In contrast, MODY3 and some of the other MODY forms are characterised by major insulin secretory defects and severe hyperglycaemia associated with microvascular complications. |
| 866 | 11984998 | Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of type 2 diabetes characterised by an early onset, an autosomal dominant inheritance, and a primary defect in insulin secretion. |
| 867 | 11984998 | So far, six MODY genes have been identified (MODY1-6): hepatocyte nuclear factor (HNF-4 alpha), glucokinase, HNF-1 alpha, HNF-1 beta, insulin promoter factor 1(IPF-1), and neurogenic differentiation factor 1 (NEUROD1). |
| 868 | 11984998 | MODY2 and MODY3 are the most common forms of MODY. |
| 869 | 11984998 | In contrast, MODY3 and some of the other MODY forms are characterised by major insulin secretory defects and severe hyperglycaemia associated with microvascular complications. |
| 870 | 11984998 | Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of type 2 diabetes characterised by an early onset, an autosomal dominant inheritance, and a primary defect in insulin secretion. |
| 871 | 11984998 | So far, six MODY genes have been identified (MODY1-6): hepatocyte nuclear factor (HNF-4 alpha), glucokinase, HNF-1 alpha, HNF-1 beta, insulin promoter factor 1(IPF-1), and neurogenic differentiation factor 1 (NEUROD1). |
| 872 | 11984998 | MODY2 and MODY3 are the most common forms of MODY. |
| 873 | 11984998 | In contrast, MODY3 and some of the other MODY forms are characterised by major insulin secretory defects and severe hyperglycaemia associated with microvascular complications. |
| 874 | 11984998 | Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of type 2 diabetes characterised by an early onset, an autosomal dominant inheritance, and a primary defect in insulin secretion. |
| 875 | 11984998 | So far, six MODY genes have been identified (MODY1-6): hepatocyte nuclear factor (HNF-4 alpha), glucokinase, HNF-1 alpha, HNF-1 beta, insulin promoter factor 1(IPF-1), and neurogenic differentiation factor 1 (NEUROD1). |
| 876 | 11984998 | MODY2 and MODY3 are the most common forms of MODY. |
| 877 | 11984998 | In contrast, MODY3 and some of the other MODY forms are characterised by major insulin secretory defects and severe hyperglycaemia associated with microvascular complications. |
| 878 | 11994285 | Activation of the insulin gene promoter through a direct effect of hepatocyte nuclear factor 4 alpha. |
| 879 | 11994285 | Maturity onset diabetes of the young, subtype 1 (MODY1), is associated with defective glucose-dependent insulin secretion from pancreatic beta cells. |
| 880 | 11994285 | To understand better the MODY1 phenotype, we tested whether HNF4 alpha was able to modulate directly the insulin gene promoter. |
| 881 | 11994285 | Transfection of cultured 293T cells with an HNF4 alpha expression vector led to 10-fold activation of a cotransfected reporter plasmid containing the rat insulin I gene promoter. |
| 882 | 11994285 | In transfected INS-1 beta cells, mutation of either the HNF1 alpha site or the HNF4 alpha site in the insulin gene promoter led to 50-75% reduction in reporter gene activity; expression of dominant negative HNF4 alpha led to significant reduction in the activity of wild type and both mutated promoters. |
| 883 | 11994285 | Thus, in addition to the previously described indirect action of HNF4 alpha on insulin gene expression mediated through elevated HNF1 alpha levels, HNF4 alpha also activates the insulin gene directly, through a previously unrecognized cis element. |
| 884 | 11994285 | Activation of the insulin gene promoter through a direct effect of hepatocyte nuclear factor 4 alpha. |
| 885 | 11994285 | Maturity onset diabetes of the young, subtype 1 (MODY1), is associated with defective glucose-dependent insulin secretion from pancreatic beta cells. |
| 886 | 11994285 | To understand better the MODY1 phenotype, we tested whether HNF4 alpha was able to modulate directly the insulin gene promoter. |
| 887 | 11994285 | Transfection of cultured 293T cells with an HNF4 alpha expression vector led to 10-fold activation of a cotransfected reporter plasmid containing the rat insulin I gene promoter. |
| 888 | 11994285 | In transfected INS-1 beta cells, mutation of either the HNF1 alpha site or the HNF4 alpha site in the insulin gene promoter led to 50-75% reduction in reporter gene activity; expression of dominant negative HNF4 alpha led to significant reduction in the activity of wild type and both mutated promoters. |
| 889 | 11994285 | Thus, in addition to the previously described indirect action of HNF4 alpha on insulin gene expression mediated through elevated HNF1 alpha levels, HNF4 alpha also activates the insulin gene directly, through a previously unrecognized cis element. |
| 890 | 11994285 | Activation of the insulin gene promoter through a direct effect of hepatocyte nuclear factor 4 alpha. |
| 891 | 11994285 | Maturity onset diabetes of the young, subtype 1 (MODY1), is associated with defective glucose-dependent insulin secretion from pancreatic beta cells. |
| 892 | 11994285 | To understand better the MODY1 phenotype, we tested whether HNF4 alpha was able to modulate directly the insulin gene promoter. |
| 893 | 11994285 | Transfection of cultured 293T cells with an HNF4 alpha expression vector led to 10-fold activation of a cotransfected reporter plasmid containing the rat insulin I gene promoter. |
| 894 | 11994285 | In transfected INS-1 beta cells, mutation of either the HNF1 alpha site or the HNF4 alpha site in the insulin gene promoter led to 50-75% reduction in reporter gene activity; expression of dominant negative HNF4 alpha led to significant reduction in the activity of wild type and both mutated promoters. |
| 895 | 11994285 | Thus, in addition to the previously described indirect action of HNF4 alpha on insulin gene expression mediated through elevated HNF1 alpha levels, HNF4 alpha also activates the insulin gene directly, through a previously unrecognized cis element. |
| 896 | 11994285 | Activation of the insulin gene promoter through a direct effect of hepatocyte nuclear factor 4 alpha. |
| 897 | 11994285 | Maturity onset diabetes of the young, subtype 1 (MODY1), is associated with defective glucose-dependent insulin secretion from pancreatic beta cells. |
| 898 | 11994285 | To understand better the MODY1 phenotype, we tested whether HNF4 alpha was able to modulate directly the insulin gene promoter. |
| 899 | 11994285 | Transfection of cultured 293T cells with an HNF4 alpha expression vector led to 10-fold activation of a cotransfected reporter plasmid containing the rat insulin I gene promoter. |
| 900 | 11994285 | In transfected INS-1 beta cells, mutation of either the HNF1 alpha site or the HNF4 alpha site in the insulin gene promoter led to 50-75% reduction in reporter gene activity; expression of dominant negative HNF4 alpha led to significant reduction in the activity of wild type and both mutated promoters. |
| 901 | 11994285 | Thus, in addition to the previously described indirect action of HNF4 alpha on insulin gene expression mediated through elevated HNF1 alpha levels, HNF4 alpha also activates the insulin gene directly, through a previously unrecognized cis element. |
| 902 | 11994285 | Activation of the insulin gene promoter through a direct effect of hepatocyte nuclear factor 4 alpha. |
| 903 | 11994285 | Maturity onset diabetes of the young, subtype 1 (MODY1), is associated with defective glucose-dependent insulin secretion from pancreatic beta cells. |
| 904 | 11994285 | To understand better the MODY1 phenotype, we tested whether HNF4 alpha was able to modulate directly the insulin gene promoter. |
| 905 | 11994285 | Transfection of cultured 293T cells with an HNF4 alpha expression vector led to 10-fold activation of a cotransfected reporter plasmid containing the rat insulin I gene promoter. |
| 906 | 11994285 | In transfected INS-1 beta cells, mutation of either the HNF1 alpha site or the HNF4 alpha site in the insulin gene promoter led to 50-75% reduction in reporter gene activity; expression of dominant negative HNF4 alpha led to significant reduction in the activity of wild type and both mutated promoters. |
| 907 | 11994285 | Thus, in addition to the previously described indirect action of HNF4 alpha on insulin gene expression mediated through elevated HNF1 alpha levels, HNF4 alpha also activates the insulin gene directly, through a previously unrecognized cis element. |
| 908 | 11994285 | Activation of the insulin gene promoter through a direct effect of hepatocyte nuclear factor 4 alpha. |
| 909 | 11994285 | Maturity onset diabetes of the young, subtype 1 (MODY1), is associated with defective glucose-dependent insulin secretion from pancreatic beta cells. |
| 910 | 11994285 | To understand better the MODY1 phenotype, we tested whether HNF4 alpha was able to modulate directly the insulin gene promoter. |
| 911 | 11994285 | Transfection of cultured 293T cells with an HNF4 alpha expression vector led to 10-fold activation of a cotransfected reporter plasmid containing the rat insulin I gene promoter. |
| 912 | 11994285 | In transfected INS-1 beta cells, mutation of either the HNF1 alpha site or the HNF4 alpha site in the insulin gene promoter led to 50-75% reduction in reporter gene activity; expression of dominant negative HNF4 alpha led to significant reduction in the activity of wild type and both mutated promoters. |
| 913 | 11994285 | Thus, in addition to the previously described indirect action of HNF4 alpha on insulin gene expression mediated through elevated HNF1 alpha levels, HNF4 alpha also activates the insulin gene directly, through a previously unrecognized cis element. |
| 914 | 11994408 | Pdx1 restores beta cell function in Irs2 knockout mice. |
| 915 | 11994408 | Mutations in Pdx1 or upstream hepatocyte nuclear factors cause autosomal forms of early-onset diabetes (maturity-onset diabetes of the young [MODY]). |
| 916 | 11994408 | In mice, the Irs2 branch of the insulin/Igf signaling system mediates peripheral insulin action and pancreatic beta cell growth and function. |
| 917 | 11994408 | To investigate whether beta cell failure in Irs2(-/-) mice might be related to dysfunction of MODY-related transcription factors, we measured the expression of Pdx1 in islets from young Irs2(-/-) mice. |
| 918 | 11994408 | Before the onset of diabetes, Pdx1 was reduced in islets from Irs2(-/-) mice, whereas it was expressed normally in islets from wild-type or Irs1(-/-) mice, which do not develop diabetes. |
| 919 | 11994408 | Whereas male Irs2(-/-)Pdx1(+/+) mice developed diabetes between 8 and 10 weeks of age, haploinsufficiency for Pdx1 caused diabetes in newborn Irs2(-/-) mice. |
| 920 | 11994408 | By contrast, transgenic expression of Pdx1 restored beta cell mass and function in Irs2(-/-) mice and promoted glucose tolerance throughout life, as these mice survived for at least 20 months without diabetes. |
| 921 | 11994408 | Our results suggest that dysregulation of Pdx1 might represent a common link between ordinary type 2 diabetes and MODY. |
| 922 | 11994408 | Pdx1 restores beta cell function in Irs2 knockout mice. |
| 923 | 11994408 | Mutations in Pdx1 or upstream hepatocyte nuclear factors cause autosomal forms of early-onset diabetes (maturity-onset diabetes of the young [MODY]). |
| 924 | 11994408 | In mice, the Irs2 branch of the insulin/Igf signaling system mediates peripheral insulin action and pancreatic beta cell growth and function. |
| 925 | 11994408 | To investigate whether beta cell failure in Irs2(-/-) mice might be related to dysfunction of MODY-related transcription factors, we measured the expression of Pdx1 in islets from young Irs2(-/-) mice. |
| 926 | 11994408 | Before the onset of diabetes, Pdx1 was reduced in islets from Irs2(-/-) mice, whereas it was expressed normally in islets from wild-type or Irs1(-/-) mice, which do not develop diabetes. |
| 927 | 11994408 | Whereas male Irs2(-/-)Pdx1(+/+) mice developed diabetes between 8 and 10 weeks of age, haploinsufficiency for Pdx1 caused diabetes in newborn Irs2(-/-) mice. |
| 928 | 11994408 | By contrast, transgenic expression of Pdx1 restored beta cell mass and function in Irs2(-/-) mice and promoted glucose tolerance throughout life, as these mice survived for at least 20 months without diabetes. |
| 929 | 11994408 | Our results suggest that dysregulation of Pdx1 might represent a common link between ordinary type 2 diabetes and MODY. |
| 930 | 11994408 | Pdx1 restores beta cell function in Irs2 knockout mice. |
| 931 | 11994408 | Mutations in Pdx1 or upstream hepatocyte nuclear factors cause autosomal forms of early-onset diabetes (maturity-onset diabetes of the young [MODY]). |
| 932 | 11994408 | In mice, the Irs2 branch of the insulin/Igf signaling system mediates peripheral insulin action and pancreatic beta cell growth and function. |
| 933 | 11994408 | To investigate whether beta cell failure in Irs2(-/-) mice might be related to dysfunction of MODY-related transcription factors, we measured the expression of Pdx1 in islets from young Irs2(-/-) mice. |
| 934 | 11994408 | Before the onset of diabetes, Pdx1 was reduced in islets from Irs2(-/-) mice, whereas it was expressed normally in islets from wild-type or Irs1(-/-) mice, which do not develop diabetes. |
| 935 | 11994408 | Whereas male Irs2(-/-)Pdx1(+/+) mice developed diabetes between 8 and 10 weeks of age, haploinsufficiency for Pdx1 caused diabetes in newborn Irs2(-/-) mice. |
| 936 | 11994408 | By contrast, transgenic expression of Pdx1 restored beta cell mass and function in Irs2(-/-) mice and promoted glucose tolerance throughout life, as these mice survived for at least 20 months without diabetes. |
| 937 | 11994408 | Our results suggest that dysregulation of Pdx1 might represent a common link between ordinary type 2 diabetes and MODY. |
| 938 | 12050210 | Twenty-two unrelated pediatric MODY patients and 97 relatives were screened for mutations in the coding region of the glucokinase (GCK), hepatic nuclear factor- HNF-1alpha and HNF4alpha genes using PCR-single strand conformation polymorphism and/or direct sequencing. |
| 939 | 12050210 | Mutations in the GCK/MODY2 gene are the most common cause of MODY in our population as recruited from pediatric and adolescent index patients. |
| 940 | 12050210 | Clinical expression of MODY3 and MODY1 mutations, the second and third groups of defects found, was more severe, including the frequent development of chronic complications. |
| 941 | 12050210 | Twenty-two unrelated pediatric MODY patients and 97 relatives were screened for mutations in the coding region of the glucokinase (GCK), hepatic nuclear factor- HNF-1alpha and HNF4alpha genes using PCR-single strand conformation polymorphism and/or direct sequencing. |
| 942 | 12050210 | Mutations in the GCK/MODY2 gene are the most common cause of MODY in our population as recruited from pediatric and adolescent index patients. |
| 943 | 12050210 | Clinical expression of MODY3 and MODY1 mutations, the second and third groups of defects found, was more severe, including the frequent development of chronic complications. |
| 944 | 12050210 | Twenty-two unrelated pediatric MODY patients and 97 relatives were screened for mutations in the coding region of the glucokinase (GCK), hepatic nuclear factor- HNF-1alpha and HNF4alpha genes using PCR-single strand conformation polymorphism and/or direct sequencing. |
| 945 | 12050210 | Mutations in the GCK/MODY2 gene are the most common cause of MODY in our population as recruited from pediatric and adolescent index patients. |
| 946 | 12050210 | Clinical expression of MODY3 and MODY1 mutations, the second and third groups of defects found, was more severe, including the frequent development of chronic complications. |
| 947 | 12083813 | An enhancer element has recently been characterized 6 kb 5' of the HNF4alpha P1 promoter containing binding sites for the transcription factors HNF1, HNF4, HNF3, and C/EBP, which are overlapped by glucocorticoid consensus sites. |
| 948 | 12086970 | Maturity-onset diabetes of the young (MODY) is a monogenic dominantly inherited form of diabetes that is characterized by defective insulin secretion from the pancreatic beta-cells. |
| 949 | 12110948 | Mutations in hepatocyte nuclear factor 4alpha (HNF4alpha) gene associated with diabetes result in greater loss of HNF4alpha function in pancreatic beta-cells than in nonpancreatic beta-cells and in reduced activation of the apolipoprotein CIII promoter in hepatic cells. |
| 950 | 12110948 | The R324H mutation had no effect on HNF4alpha function with either the HNF1alpha and L-type pyruvate kinase (LPK) promoters, but the D126Y and D126H mutations impaired HNF4alpha transcriptional activities in all tested cell lines. |
| 951 | 12110948 | Mutations in hepatocyte nuclear factor 4alpha (HNF4alpha) gene associated with diabetes result in greater loss of HNF4alpha function in pancreatic beta-cells than in nonpancreatic beta-cells and in reduced activation of the apolipoprotein CIII promoter in hepatic cells. |
| 952 | 12110948 | The R324H mutation had no effect on HNF4alpha function with either the HNF1alpha and L-type pyruvate kinase (LPK) promoters, but the D126Y and D126H mutations impaired HNF4alpha transcriptional activities in all tested cell lines. |
| 953 | 12145145 | Haploinsufficiency of HNF-1alpha or HNF-4alpha results in MODY because of defective function of pancreatic islet cells. |
| 954 | 12145145 | The network contains an indispensable core component formed by a positive cross-regulatory feedback circuit between HNF-1alpha and HNF-4alpha. |
| 955 | 12145145 | However, the loss of one HNF-1alpha or HNF-4alpha allele can increase the probability that the feedback circuit is permanently switched off, resulting in decreased expression of all four alleles selectively in beta-cells. |
| 956 | 12145145 | Haploinsufficiency of HNF-1alpha or HNF-4alpha results in MODY because of defective function of pancreatic islet cells. |
| 957 | 12145145 | The network contains an indispensable core component formed by a positive cross-regulatory feedback circuit between HNF-1alpha and HNF-4alpha. |
| 958 | 12145145 | However, the loss of one HNF-1alpha or HNF-4alpha allele can increase the probability that the feedback circuit is permanently switched off, resulting in decreased expression of all four alleles selectively in beta-cells. |
| 959 | 12145145 | Haploinsufficiency of HNF-1alpha or HNF-4alpha results in MODY because of defective function of pancreatic islet cells. |
| 960 | 12145145 | The network contains an indispensable core component formed by a positive cross-regulatory feedback circuit between HNF-1alpha and HNF-4alpha. |
| 961 | 12145145 | However, the loss of one HNF-1alpha or HNF-4alpha allele can increase the probability that the feedback circuit is permanently switched off, resulting in decreased expression of all four alleles selectively in beta-cells. |
| 962 | 12173691 | Maturity-onset diabetes of the young (MODY) is a genetic subgroup of diabetes characterised by an autosomal dominant inheritance and early onset, non-insulin dependent diabetes. |
| 963 | 12173691 | Patients with mutation in genes encoding the transcription factors, hepatocyte nuclear factor (HNF)- 1alpha, HNF-4alpha, HNF-1beta and insulin promoter factor 1 (IPF-1) have a common progressive beta-cell failure resulting in increasing hyperglycaemia and treatment requirements. |
| 964 | 12173691 | Patients with transcription factor mutations have a range of discrete extra-pancreatic phenotypes including a low renal threshold for glucose with HNF-1alpha mutations, altered lipids and lipoproteins with HNF-4alpha mutations and a variety of cystic renal diseases and uterine and genital developmental disorders with HNF-1beta mutations. |
| 965 | 12173691 | Maturity-onset diabetes of the young (MODY) is a genetic subgroup of diabetes characterised by an autosomal dominant inheritance and early onset, non-insulin dependent diabetes. |
| 966 | 12173691 | Patients with mutation in genes encoding the transcription factors, hepatocyte nuclear factor (HNF)- 1alpha, HNF-4alpha, HNF-1beta and insulin promoter factor 1 (IPF-1) have a common progressive beta-cell failure resulting in increasing hyperglycaemia and treatment requirements. |
| 967 | 12173691 | Patients with transcription factor mutations have a range of discrete extra-pancreatic phenotypes including a low renal threshold for glucose with HNF-1alpha mutations, altered lipids and lipoproteins with HNF-4alpha mutations and a variety of cystic renal diseases and uterine and genital developmental disorders with HNF-1beta mutations. |
| 968 | 12173691 | Maturity-onset diabetes of the young (MODY) is a genetic subgroup of diabetes characterised by an autosomal dominant inheritance and early onset, non-insulin dependent diabetes. |
| 969 | 12173691 | Patients with mutation in genes encoding the transcription factors, hepatocyte nuclear factor (HNF)- 1alpha, HNF-4alpha, HNF-1beta and insulin promoter factor 1 (IPF-1) have a common progressive beta-cell failure resulting in increasing hyperglycaemia and treatment requirements. |
| 970 | 12173691 | Patients with transcription factor mutations have a range of discrete extra-pancreatic phenotypes including a low renal threshold for glucose with HNF-1alpha mutations, altered lipids and lipoproteins with HNF-4alpha mutations and a variety of cystic renal diseases and uterine and genital developmental disorders with HNF-1beta mutations. |
| 971 | 12203996 | Several genes are known to induce MODY : HNF4A/MODY1, GCK/MODY2, TCF1/MODY3, IPF1/MODY4, TCF2/MODY5 and NEUROD1/MODY6. |
| 972 | 12235114 | Mutations in the genes encoding hepatocyte nuclear factor 4alpha (HNF-4alpha) and HNF-1alpha impair insulin secretion and cause maturity onset diabetes of the young (MODY). |
| 973 | 12235114 | HNF-4alpha is known to be an essential positive regulator of HNF-1alpha. |
| 974 | 12235114 | More recent data demonstrates that HNF-4alpha expression is dependent on HNF-1alpha in mouse pancreatic islets and exocrine cells. |
| 975 | 12235114 | This effect is mediated by binding of HNF-1alpha to a tissue-specific promoter (P2) located 45.6 kb upstream from the previously characterized Hnf4alpha promoter (P1). |
| 976 | 12235114 | These findings provide genetic evidence that HNF-1alpha serves as an upstream regulator of HNF-4alpha and interacts directly with the P2 promoter in human pancreatic cells. |
| 977 | 12235114 | Mutations in the genes encoding hepatocyte nuclear factor 4alpha (HNF-4alpha) and HNF-1alpha impair insulin secretion and cause maturity onset diabetes of the young (MODY). |
| 978 | 12235114 | HNF-4alpha is known to be an essential positive regulator of HNF-1alpha. |
| 979 | 12235114 | More recent data demonstrates that HNF-4alpha expression is dependent on HNF-1alpha in mouse pancreatic islets and exocrine cells. |
| 980 | 12235114 | This effect is mediated by binding of HNF-1alpha to a tissue-specific promoter (P2) located 45.6 kb upstream from the previously characterized Hnf4alpha promoter (P1). |
| 981 | 12235114 | These findings provide genetic evidence that HNF-1alpha serves as an upstream regulator of HNF-4alpha and interacts directly with the P2 promoter in human pancreatic cells. |
| 982 | 12235114 | Mutations in the genes encoding hepatocyte nuclear factor 4alpha (HNF-4alpha) and HNF-1alpha impair insulin secretion and cause maturity onset diabetes of the young (MODY). |
| 983 | 12235114 | HNF-4alpha is known to be an essential positive regulator of HNF-1alpha. |
| 984 | 12235114 | More recent data demonstrates that HNF-4alpha expression is dependent on HNF-1alpha in mouse pancreatic islets and exocrine cells. |
| 985 | 12235114 | This effect is mediated by binding of HNF-1alpha to a tissue-specific promoter (P2) located 45.6 kb upstream from the previously characterized Hnf4alpha promoter (P1). |
| 986 | 12235114 | These findings provide genetic evidence that HNF-1alpha serves as an upstream regulator of HNF-4alpha and interacts directly with the P2 promoter in human pancreatic cells. |
| 987 | 12235114 | Mutations in the genes encoding hepatocyte nuclear factor 4alpha (HNF-4alpha) and HNF-1alpha impair insulin secretion and cause maturity onset diabetes of the young (MODY). |
| 988 | 12235114 | HNF-4alpha is known to be an essential positive regulator of HNF-1alpha. |
| 989 | 12235114 | More recent data demonstrates that HNF-4alpha expression is dependent on HNF-1alpha in mouse pancreatic islets and exocrine cells. |
| 990 | 12235114 | This effect is mediated by binding of HNF-1alpha to a tissue-specific promoter (P2) located 45.6 kb upstream from the previously characterized Hnf4alpha promoter (P1). |
| 991 | 12235114 | These findings provide genetic evidence that HNF-1alpha serves as an upstream regulator of HNF-4alpha and interacts directly with the P2 promoter in human pancreatic cells. |
| 992 | 12235114 | Mutations in the genes encoding hepatocyte nuclear factor 4alpha (HNF-4alpha) and HNF-1alpha impair insulin secretion and cause maturity onset diabetes of the young (MODY). |
| 993 | 12235114 | HNF-4alpha is known to be an essential positive regulator of HNF-1alpha. |
| 994 | 12235114 | More recent data demonstrates that HNF-4alpha expression is dependent on HNF-1alpha in mouse pancreatic islets and exocrine cells. |
| 995 | 12235114 | This effect is mediated by binding of HNF-1alpha to a tissue-specific promoter (P2) located 45.6 kb upstream from the previously characterized Hnf4alpha promoter (P1). |
| 996 | 12235114 | These findings provide genetic evidence that HNF-1alpha serves as an upstream regulator of HNF-4alpha and interacts directly with the P2 promoter in human pancreatic cells. |
| 997 | 12359128 | The study of maturity-onset diabetes of the young (MODY), an autosomal dominant form of early-onset diabetes mellitus characterised by defective insulin secretion has been extremely successful in two ways. |
| 998 | 12359128 | Five of the six MODY genes, TCF1 (encoding HNF-1alpha), TCF2 (encoding HNF-1beta) HNF4A, insulin promoter factor (IPF)1, and NEUROD1, are transcription factors that operate in a complex network of gene regulation. |
| 999 | 12359128 | This includes the co-regulation of HNF-1alpha and HNF-4alpha by each other. |
| 1000 | 12359128 | The study of maturity-onset diabetes of the young (MODY), an autosomal dominant form of early-onset diabetes mellitus characterised by defective insulin secretion has been extremely successful in two ways. |
| 1001 | 12359128 | Five of the six MODY genes, TCF1 (encoding HNF-1alpha), TCF2 (encoding HNF-1beta) HNF4A, insulin promoter factor (IPF)1, and NEUROD1, are transcription factors that operate in a complex network of gene regulation. |
| 1002 | 12359128 | This includes the co-regulation of HNF-1alpha and HNF-4alpha by each other. |
| 1003 | 12359128 | The study of maturity-onset diabetes of the young (MODY), an autosomal dominant form of early-onset diabetes mellitus characterised by defective insulin secretion has been extremely successful in two ways. |
| 1004 | 12359128 | Five of the six MODY genes, TCF1 (encoding HNF-1alpha), TCF2 (encoding HNF-1beta) HNF4A, insulin promoter factor (IPF)1, and NEUROD1, are transcription factors that operate in a complex network of gene regulation. |
| 1005 | 12359128 | This includes the co-regulation of HNF-1alpha and HNF-4alpha by each other. |
| 1006 | 12475768 | In addition, HNF4a and Mybl2 were screened for mutations and new polymorphisms. |
| 1007 | 12475773 | Diabetes in subjects with hepatocyte nuclear factor (HNF)-1alpha gene mutations (maturity-onset diabetes of the young [MODY]-3) is characterized by impaired insulin secretion. |
| 1008 | 12475772 | Except for MODY2 (glucokinase), all other MODY subtypes have been linked to transcription factors. |
| 1009 | 12475772 | The existence of a regulatory circuit between HNF-4alpha and HNF-1alpha is confirmed in these cell models. |
| 1010 | 12475772 | The MODY4 gene, IPF-1 (insulin promoter factor-1)/PDX-1 (pancreas duodenum homeobox-1), controls not only the transcription of insulin but also expression of enzymes involved in its processing. |
| 1011 | 12475772 | Suppression of Pdx-1 function in INS-1 cells does not alter glucose metabolism but rather inhibits insulin release by impairing steps distal to the generation of mitochondrial coupling factors. |
| 1012 | 12475772 | Except for MODY2 (glucokinase), all other MODY subtypes have been linked to transcription factors. |
| 1013 | 12475772 | The existence of a regulatory circuit between HNF-4alpha and HNF-1alpha is confirmed in these cell models. |
| 1014 | 12475772 | The MODY4 gene, IPF-1 (insulin promoter factor-1)/PDX-1 (pancreas duodenum homeobox-1), controls not only the transcription of insulin but also expression of enzymes involved in its processing. |
| 1015 | 12475772 | Suppression of Pdx-1 function in INS-1 cells does not alter glucose metabolism but rather inhibits insulin release by impairing steps distal to the generation of mitochondrial coupling factors. |
| 1016 | 12606533 | Maturity-onset diabetes of the young (MODY) is a heterogeneous single gene disorder characterized by non-insulin-dependent diabetes, an early onset and autosomal dominant inheritance. |
| 1017 | 12618086 | Mutations in the HNF1-alpha gene cause maturity-onset diabetes of the young (MODY), but the exact mechanism is not known. |
| 1018 | 12618086 | These were 92bp upstream of SLC3A1, 52bp upstream of PCBD (DCOH), and 42202bp upstream of TCF2(HNF1-beta). |
| 1019 | 12627330 | Genetic epidemiology of MODY in the Czech republic: new mutations in the MODY genes HNF-4alpha, GCK and HNF-1alpha. |
| 1020 | 12643132 | Maturity-onset diabetes of the young (MODY) are monogenic forms of type 2 diabetes that are characterized by an early disease onset, autosomal-dominant inheritance, and defects in insulin secretion. |
| 1021 | 12643132 | The majority of the MODY subtypes are caused by mutations in transcription factors that include hepatocyte nuclear factor (HNF)-4 alpha, HNF-1 alpha, PDX-1, HNF-1 beta, and NEURO-DI/BETA-2. |
| 1022 | 12643132 | In addition, genetic defects in the glucokinase gene, the glucose sensor of the pancreatic beta cells, and the insulin gene also lead to impaired glucose tolerance. |
| 1023 | 12643132 | Maturity-onset diabetes of the young (MODY) are monogenic forms of type 2 diabetes that are characterized by an early disease onset, autosomal-dominant inheritance, and defects in insulin secretion. |
| 1024 | 12643132 | The majority of the MODY subtypes are caused by mutations in transcription factors that include hepatocyte nuclear factor (HNF)-4 alpha, HNF-1 alpha, PDX-1, HNF-1 beta, and NEURO-DI/BETA-2. |
| 1025 | 12643132 | In addition, genetic defects in the glucokinase gene, the glucose sensor of the pancreatic beta cells, and the insulin gene also lead to impaired glucose tolerance. |
| 1026 | 12646418 | HNF-1alpha and endodermal transcription factors cooperatively activate Fabpl: MODY3 mutations abrogate cooperativity. |
| 1027 | 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. |
| 1028 | 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. |
| 1029 | 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. |
| 1030 | 12697672 | Due to the presence of the activation function module AF-1, HNF4 alpha isoforms originating from the P1 promoter exhibit stronger transcriptional activities and recruit coactivators more efficiently than isoforms driven by the P2 promoter. |
| 1031 | 12716764 | The orphan receptor small heterodimer partner (SHP, NR0B2) modulates the transcription activity of the MODY1 gene HNF4a. |
| 1032 | 12740371 | AMP-activated protein kinase regulates HNF4alpha transcriptional activity by inhibiting dimer formation and decreasing protein stability. |
| 1033 | 12740371 | The transcription factor hepatic nuclear factor 4alpha (HNF4alpha) is an orphan nuclear receptor that regulates the expression of genes involved in energy metabolism in the liver, intestine, and endocrine pancreas. |
| 1034 | 12740371 | Here we demonstrate that AMPK directly phosphorylates HNF4alpha and represses its transcriptional activity. |
| 1035 | 12740371 | AMPK-mediated phosphorylation of HNF4alpha on serine 304 had a 2-fold effect, reducing the ability of the transcription factor to form homodimers and bind DNA and increasing its degradation rate in vivo. |
| 1036 | 12740371 | These results demonstrate that HNF4alpha is a downstream target of AMPK and raise the possibility that one of the effects of AMPK activation is reduced expression of HNF4alpha target genes. |
| 1037 | 12740371 | AMP-activated protein kinase regulates HNF4alpha transcriptional activity by inhibiting dimer formation and decreasing protein stability. |
| 1038 | 12740371 | The transcription factor hepatic nuclear factor 4alpha (HNF4alpha) is an orphan nuclear receptor that regulates the expression of genes involved in energy metabolism in the liver, intestine, and endocrine pancreas. |
| 1039 | 12740371 | Here we demonstrate that AMPK directly phosphorylates HNF4alpha and represses its transcriptional activity. |
| 1040 | 12740371 | AMPK-mediated phosphorylation of HNF4alpha on serine 304 had a 2-fold effect, reducing the ability of the transcription factor to form homodimers and bind DNA and increasing its degradation rate in vivo. |
| 1041 | 12740371 | These results demonstrate that HNF4alpha is a downstream target of AMPK and raise the possibility that one of the effects of AMPK activation is reduced expression of HNF4alpha target genes. |
| 1042 | 12740371 | AMP-activated protein kinase regulates HNF4alpha transcriptional activity by inhibiting dimer formation and decreasing protein stability. |
| 1043 | 12740371 | The transcription factor hepatic nuclear factor 4alpha (HNF4alpha) is an orphan nuclear receptor that regulates the expression of genes involved in energy metabolism in the liver, intestine, and endocrine pancreas. |
| 1044 | 12740371 | Here we demonstrate that AMPK directly phosphorylates HNF4alpha and represses its transcriptional activity. |
| 1045 | 12740371 | AMPK-mediated phosphorylation of HNF4alpha on serine 304 had a 2-fold effect, reducing the ability of the transcription factor to form homodimers and bind DNA and increasing its degradation rate in vivo. |
| 1046 | 12740371 | These results demonstrate that HNF4alpha is a downstream target of AMPK and raise the possibility that one of the effects of AMPK activation is reduced expression of HNF4alpha target genes. |
| 1047 | 12740371 | AMP-activated protein kinase regulates HNF4alpha transcriptional activity by inhibiting dimer formation and decreasing protein stability. |
| 1048 | 12740371 | The transcription factor hepatic nuclear factor 4alpha (HNF4alpha) is an orphan nuclear receptor that regulates the expression of genes involved in energy metabolism in the liver, intestine, and endocrine pancreas. |
| 1049 | 12740371 | Here we demonstrate that AMPK directly phosphorylates HNF4alpha and represses its transcriptional activity. |
| 1050 | 12740371 | AMPK-mediated phosphorylation of HNF4alpha on serine 304 had a 2-fold effect, reducing the ability of the transcription factor to form homodimers and bind DNA and increasing its degradation rate in vivo. |
| 1051 | 12740371 | These results demonstrate that HNF4alpha is a downstream target of AMPK and raise the possibility that one of the effects of AMPK activation is reduced expression of HNF4alpha target genes. |
| 1052 | 12740371 | AMP-activated protein kinase regulates HNF4alpha transcriptional activity by inhibiting dimer formation and decreasing protein stability. |
| 1053 | 12740371 | The transcription factor hepatic nuclear factor 4alpha (HNF4alpha) is an orphan nuclear receptor that regulates the expression of genes involved in energy metabolism in the liver, intestine, and endocrine pancreas. |
| 1054 | 12740371 | Here we demonstrate that AMPK directly phosphorylates HNF4alpha and represses its transcriptional activity. |
| 1055 | 12740371 | AMPK-mediated phosphorylation of HNF4alpha on serine 304 had a 2-fold effect, reducing the ability of the transcription factor to form homodimers and bind DNA and increasing its degradation rate in vivo. |
| 1056 | 12740371 | These results demonstrate that HNF4alpha is a downstream target of AMPK and raise the possibility that one of the effects of AMPK activation is reduced expression of HNF4alpha target genes. |
| 1057 | 12807885 | Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) is a transcriptional coactivator that regulates multiple aspects of cellular energy metabolism, including mitochondrial biogenesis, hepatic gluconeogenesis, and beta-oxidation of fatty acids. |
| 1058 | 12807885 | We have recently described PGC-1beta, a novel transcriptional coactivator that is a homolog of PGC-1alpha. |
| 1059 | 12807885 | Although PGC-1beta shares significant sequence similarity and tissue distribution with PGC-1alpha, the biological activities of PGC-1beta in the regulation of cellular metabolism is unknown. |
| 1060 | 12807885 | PGC-1beta, like PGC-1alpha, potently induces the expression of an array of mitochondrial genes involved in oxidative metabolism. |
| 1061 | 12807885 | However, in contrast to PGC-1alpha, PGC-1beta poorly activates the expression of gluconeogenic genes in hepatocytes or liver in vivo, illustrating that these two coactivators play distinct roles in hepatic glucose metabolism. |
| 1062 | 12807885 | The reduced ability of PGC-1beta to induce gluconeogenic genes is due, at least in part, to its inability to physically associate with and coactivate hepatic nuclear receptor 4alpha (HNF4alpha) and forkhead transcription factor O1 (FOXO1), two critical transcription factors that mediate the activation of gluconeogenic gene expression by PGC-1alpha. |
| 1063 | 12807885 | These data illustrate that PGC-1beta and PGC-1alpha have distinct arrays of activities in hepatic energy metabolism. |
| 1064 | 12837760 | Neurogenin3 and hepatic nuclear factor 1 cooperate in activating pancreatic expression of Pax4. |
| 1065 | 12837760 | During fetal development, paired/homeodomain transcription factor Pax4 controls the formation of the insulin-producing beta cells and the somatostatin-producing delta cells in the islets of Langerhans in the pancreas. |
| 1066 | 12837760 | This short sequence contains binding sites for homeodomain transcription factors PDX1 and hepatic nuclear factor (HNF)1, nuclear receptor HNF4alpha, and basic helix-loop-helix factor Neurogenin3. |
| 1067 | 12837760 | In the current study we demonstrate that the HNF1alpha and Neurogenin3 binding sites are critical for activity of the region through synergy between the two proteins. |
| 1068 | 12837760 | Furthermore, exogenous expression of Neurogenin3 is sufficient to induce expression of the endogenous pax4 gene in the mouse pancreatic ductal cell line mPAC, which already expresses HNF1alpha, whereas expression of both Neurogenin3 and HNF1alpha are necessary to activate the pax4 gene in the fibroblast cell line NIH3T3. |
| 1069 | 12837760 | These data demonstrate how Neurogenin3 and HNF1alpha activate the pax4 gene during the cascade of gene expression events that control pancreatic endocrine cell development. |
| 1070 | 12910053 | Studies in MODY individuals and families lead to a genetic definition of MODY subtypes with profound implications for our understanding of gene mutations involved in the development of T2D through our understanding on the major role of these genes and on their transcriptional activity on b-cell development and function; and on the regulation of glucose and insulin metabolism. |
| 1071 | 14551916 | Polymorphisms in five of 15 genes (33%) encoding molecules known to primarily influence pancreatic beta-cell function-ABCC8 (sulphonylurea receptor), KCNJ11 (KIR6.2), SLC2A2 (GLUT2), HNF4A (HNF4alpha), and INS (insulin)-significantly altered disease risk, and in three genes, the risk allele, haplotype, or both had a biologically consistent effect on a relevant physiological trait in the QT study. |
| 1072 | 14551916 | We examined 35 genes predicted to have their major influence on insulin action, and three (9%)-INSR, PIK3R1, and SOS1-showed significant associations with diabetes. |
| 1073 | 14633861 | Regulation of apolipoprotein M gene expression by MODY3 gene hepatocyte nuclear factor-1alpha: haploinsufficiency is associated with reduced serum apolipoprotein M levels. |
| 1074 | 14633861 | Heterozygous mutations in the HNF-1alpha gene are responsible for maturity-onset diabetes of the young (MODY3), which is characterized by pancreatic beta-cell-deficient insulin secretion. |
| 1075 | 14633861 | In this study, we show that Hnf-1alpha is a potent transcriptional activator of the gene encoding apolipoprotein M (apoM), a lipoprotein that is associated with the HDL particle. |
| 1076 | 14633861 | Mutant Hnf-1alpha(-/-) mice completely lack expression of apoM in the liver and the kidney. |
| 1077 | 14633861 | Serum apoM levels in Hnf-1alpha(+/-) mice are reduced approximately 50% compared with wild-type animals and are absent in the HDL and HDLc fractions of Hnf-1alpha(-/-). |
| 1078 | 14633861 | We show that Hnf-1alpha is a potent activator of the apoM promoter, that a specific mutation in the HNF-1 binding site abolished transcriptional activation of the apoM gene, and that Hnf-1alpha protein can bind to the Hnf-1 binding site of the apoM promoter in vitro. |
| 1079 | 14633861 | To investigate whether patients with mutations in HNF-1alpha mutations (MODY3) have reduced serum apoM levels, we measured apoM levels in the serum of nine HNF-1alpha/MODY3 patients, nine normal matched control subjects (HNF-1alpha(+/+)), and nine HNF-4alpha/MODY1 subjects. |
| 1080 | 14633861 | Serum levels of apoM were decreased in HNF-1alpha/MODY3 subjects when compared with control subjects (P < 0.02) as well as with HNF-4alpha/MODY1 subjects, indicating that HNF-1alpha haploinsufficiency rather than hyperglycemia is the primary cause of decreased serum apoM protein concentrations. |
| 1081 | 14633861 | This study demonstrates that HNF-1alpha is required for apoM expression in vivo and that heterozygous HNF-1alpha mutations lead to an HNF-1alpha-dependent impairment of apoM expression. |
| 1082 | 14633861 | ApoM levels may be a useful serum marker for the identification of MODY3 patients. |
| 1083 | 14633861 | Regulation of apolipoprotein M gene expression by MODY3 gene hepatocyte nuclear factor-1alpha: haploinsufficiency is associated with reduced serum apolipoprotein M levels. |
| 1084 | 14633861 | Heterozygous mutations in the HNF-1alpha gene are responsible for maturity-onset diabetes of the young (MODY3), which is characterized by pancreatic beta-cell-deficient insulin secretion. |
| 1085 | 14633861 | In this study, we show that Hnf-1alpha is a potent transcriptional activator of the gene encoding apolipoprotein M (apoM), a lipoprotein that is associated with the HDL particle. |
| 1086 | 14633861 | Mutant Hnf-1alpha(-/-) mice completely lack expression of apoM in the liver and the kidney. |
| 1087 | 14633861 | Serum apoM levels in Hnf-1alpha(+/-) mice are reduced approximately 50% compared with wild-type animals and are absent in the HDL and HDLc fractions of Hnf-1alpha(-/-). |
| 1088 | 14633861 | We show that Hnf-1alpha is a potent activator of the apoM promoter, that a specific mutation in the HNF-1 binding site abolished transcriptional activation of the apoM gene, and that Hnf-1alpha protein can bind to the Hnf-1 binding site of the apoM promoter in vitro. |
| 1089 | 14633861 | To investigate whether patients with mutations in HNF-1alpha mutations (MODY3) have reduced serum apoM levels, we measured apoM levels in the serum of nine HNF-1alpha/MODY3 patients, nine normal matched control subjects (HNF-1alpha(+/+)), and nine HNF-4alpha/MODY1 subjects. |
| 1090 | 14633861 | Serum levels of apoM were decreased in HNF-1alpha/MODY3 subjects when compared with control subjects (P < 0.02) as well as with HNF-4alpha/MODY1 subjects, indicating that HNF-1alpha haploinsufficiency rather than hyperglycemia is the primary cause of decreased serum apoM protein concentrations. |
| 1091 | 14633861 | This study demonstrates that HNF-1alpha is required for apoM expression in vivo and that heterozygous HNF-1alpha mutations lead to an HNF-1alpha-dependent impairment of apoM expression. |
| 1092 | 14633861 | ApoM levels may be a useful serum marker for the identification of MODY3 patients. |
| 1093 | 14654354 | Characterization of the human glycerol kinase promoter: identification of a functional HNF-4alpha binding site and evidence for transcriptional activation. |
| 1094 | 14654354 | Mutations in the GK gene result in a rare inborn error of metabolism, GK deficiency (GKD), and at least one of these mutations (N288D) is associated with insulin resistance and diabetes mellitus. |
| 1095 | 14654354 | The involvement of both GK and HNF-4alpha in the etiology of diabetes mellitus is intriguing, and we speculate that HNF-4alpha represents a potential modifier of the GKD phenotype. |
| 1096 | 14654354 | Characterization of the human glycerol kinase promoter: identification of a functional HNF-4alpha binding site and evidence for transcriptional activation. |
| 1097 | 14654354 | Mutations in the GK gene result in a rare inborn error of metabolism, GK deficiency (GKD), and at least one of these mutations (N288D) is associated with insulin resistance and diabetes mellitus. |
| 1098 | 14654354 | The involvement of both GK and HNF-4alpha in the etiology of diabetes mellitus is intriguing, and we speculate that HNF-4alpha represents a potential modifier of the GKD phenotype. |
| 1099 | 14694850 | Major break-throughs in the genetic sciences of type 2 diabetes have been identifications of insulin receptor gene mutations in syndromes of severe insulin resistance and mutations in pancreatic beta-cell genes in the monogenic sub-group of type 2 diabetes: maturity-onset-diabetes-of-the-young, MODY. |
| 1100 | 14694850 | The studies reported in this thesis are excerpts from an extensive strategy of genetically dissecting (mutation analysis) in: 1) patients with the common form of late-onset type 2 diabetes mellitus the pathways that transduce the insulin signals from the plasma membrane to the activation of glycogen synthesis in skeletal muscle, and in 2) patients with either late-onset type diabetes or MODY the pathways involved in normal beta-cell development and beta-cell function (insulin secretion). |
| 1101 | 14694850 | We could not confirm that a Val985Met variant in the insulin receptor is associated with type 2 diabetes or that the Met326Val of the p85 alpha regulatory subunit of the phosphoinositide-3 kinase is associated with insulin resistance. |
| 1102 | 14694850 | We found no coding mutations (missense) in the insulin signalling protein kinases but we confirmed that the 5 bp deletion (PP1ARE) in the 3'-end of the PPP1R3 gene that encodes the glycogen-associated regulatory subunit of protein phosphatase-1 (PP1G) is associated with insulin resistance estimated as insulin mediated glucose uptake. |
| 1103 | 14694850 | In contrast to protein kinases in skeletal muscles the genes encoding beta-cell transcription factors (IPF-1, NeuroD1/BETA2, and Neurogenin 3) are polymorphic but we could not confirm that the Asp76Asn of IPF-1 is a susceptibility gene for late-onset type 2 diabetes. |
| 1104 | 14694850 | On the other hand we confirmed that the Ala45Thr variant in NeuroD1/BETA2 may represent a susceptibility gene for type 1 diabetes but none of these genes revealed any MODY-specific mutations. |
| 1105 | 14694850 | Also the gene encoding the ATP-regulatable potassium channels of the beta-cell (Kir6.2) is polymorphic but none of these polymorphisms associated with changes in glucose-induced insulin secretion. |
| 1106 | 14694850 | Major break-throughs in the genetic sciences of type 2 diabetes have been identifications of insulin receptor gene mutations in syndromes of severe insulin resistance and mutations in pancreatic beta-cell genes in the monogenic sub-group of type 2 diabetes: maturity-onset-diabetes-of-the-young, MODY. |
| 1107 | 14694850 | The studies reported in this thesis are excerpts from an extensive strategy of genetically dissecting (mutation analysis) in: 1) patients with the common form of late-onset type 2 diabetes mellitus the pathways that transduce the insulin signals from the plasma membrane to the activation of glycogen synthesis in skeletal muscle, and in 2) patients with either late-onset type diabetes or MODY the pathways involved in normal beta-cell development and beta-cell function (insulin secretion). |
| 1108 | 14694850 | We could not confirm that a Val985Met variant in the insulin receptor is associated with type 2 diabetes or that the Met326Val of the p85 alpha regulatory subunit of the phosphoinositide-3 kinase is associated with insulin resistance. |
| 1109 | 14694850 | We found no coding mutations (missense) in the insulin signalling protein kinases but we confirmed that the 5 bp deletion (PP1ARE) in the 3'-end of the PPP1R3 gene that encodes the glycogen-associated regulatory subunit of protein phosphatase-1 (PP1G) is associated with insulin resistance estimated as insulin mediated glucose uptake. |
| 1110 | 14694850 | In contrast to protein kinases in skeletal muscles the genes encoding beta-cell transcription factors (IPF-1, NeuroD1/BETA2, and Neurogenin 3) are polymorphic but we could not confirm that the Asp76Asn of IPF-1 is a susceptibility gene for late-onset type 2 diabetes. |
| 1111 | 14694850 | On the other hand we confirmed that the Ala45Thr variant in NeuroD1/BETA2 may represent a susceptibility gene for type 1 diabetes but none of these genes revealed any MODY-specific mutations. |
| 1112 | 14694850 | Also the gene encoding the ATP-regulatable potassium channels of the beta-cell (Kir6.2) is polymorphic but none of these polymorphisms associated with changes in glucose-induced insulin secretion. |
| 1113 | 14694850 | Major break-throughs in the genetic sciences of type 2 diabetes have been identifications of insulin receptor gene mutations in syndromes of severe insulin resistance and mutations in pancreatic beta-cell genes in the monogenic sub-group of type 2 diabetes: maturity-onset-diabetes-of-the-young, MODY. |
| 1114 | 14694850 | The studies reported in this thesis are excerpts from an extensive strategy of genetically dissecting (mutation analysis) in: 1) patients with the common form of late-onset type 2 diabetes mellitus the pathways that transduce the insulin signals from the plasma membrane to the activation of glycogen synthesis in skeletal muscle, and in 2) patients with either late-onset type diabetes or MODY the pathways involved in normal beta-cell development and beta-cell function (insulin secretion). |
| 1115 | 14694850 | We could not confirm that a Val985Met variant in the insulin receptor is associated with type 2 diabetes or that the Met326Val of the p85 alpha regulatory subunit of the phosphoinositide-3 kinase is associated with insulin resistance. |
| 1116 | 14694850 | We found no coding mutations (missense) in the insulin signalling protein kinases but we confirmed that the 5 bp deletion (PP1ARE) in the 3'-end of the PPP1R3 gene that encodes the glycogen-associated regulatory subunit of protein phosphatase-1 (PP1G) is associated with insulin resistance estimated as insulin mediated glucose uptake. |
| 1117 | 14694850 | In contrast to protein kinases in skeletal muscles the genes encoding beta-cell transcription factors (IPF-1, NeuroD1/BETA2, and Neurogenin 3) are polymorphic but we could not confirm that the Asp76Asn of IPF-1 is a susceptibility gene for late-onset type 2 diabetes. |
| 1118 | 14694850 | On the other hand we confirmed that the Ala45Thr variant in NeuroD1/BETA2 may represent a susceptibility gene for type 1 diabetes but none of these genes revealed any MODY-specific mutations. |
| 1119 | 14694850 | Also the gene encoding the ATP-regulatable potassium channels of the beta-cell (Kir6.2) is polymorphic but none of these polymorphisms associated with changes in glucose-induced insulin secretion. |
| 1120 | 14741192 | These three regions were functionally characterized using the chloramphenicol acetyltransferase (CAT) reporter assay, in which the conserved 5' regions of mouse HNF-4alpha were cloned in front of the herpes simplex virus thymidine kinase promoter driving transcription of the CAT gene. |
| 1121 | 14747304 | Haploinsufficiency is therefore likely to be the most important mutational mechanism of HNF-1alpha mutations causing MODY. |
| 1122 | 14982928 | To further assess potential mechanisms of activation, we have solved a structure of human HNF-4alpha bound to both fatty acid ligand and a coactivator sequence derived from SRC-1. |
| 1123 | 14988562 | To gain insight into this circuitry, we used chromatin immunoprecipitation combined with promoter microarrays to identify systematically the genes occupied by the transcriptional regulators HNF1alpha, HNF4alpha, and HNF6, together with RNA polymerase II, in human liver and pancreatic islets. |
| 1124 | 14988562 | We identified tissue-specific regulatory circuits formed by HNF1alpha, HNF4alpha, and HNF6 with other transcription factors, revealing how these factors function as master regulators of hepatocyte and islet transcription. |
| 1125 | 14988562 | To gain insight into this circuitry, we used chromatin immunoprecipitation combined with promoter microarrays to identify systematically the genes occupied by the transcriptional regulators HNF1alpha, HNF4alpha, and HNF6, together with RNA polymerase II, in human liver and pancreatic islets. |
| 1126 | 14988562 | We identified tissue-specific regulatory circuits formed by HNF1alpha, HNF4alpha, and HNF6 with other transcription factors, revealing how these factors function as master regulators of hepatocyte and islet transcription. |
| 1127 | 15016234 | To date, five molecular causes of classic MODY have been identified: hepatocyte nuclear factor-4 alpha (HNF-4 alpha; MODY1), glucokinase (MODY2), hepatocyte nuclear factor-1 alpha (HNF-1 alpha; MODY3), insulin promoter factor-1 (IPF-1, MODY4), and hepatocyte nuclear factor-1 beta (HNF-1 beta; MODY5). |
| 1128 | 15077723 | They regulate the activity or nuclear abundance of several transcription factors, including PPAR, LXR, HNF-4, NFkappaB, and SREBP. |
| 1129 | 15107844 | PGC-1 promotes insulin resistance in liver through PPAR-alpha-dependent induction of TRB-3. |
| 1130 | 15107844 | The nuclear hormone receptor coactivator PGC-1 (peroxisome proliferator-activated (PPAR)-gamma coactivator-1) has been implicated in the onset of type 2 diabetes. |
| 1131 | 15107844 | Hepatic PGC-1 expression is elevated in mouse models of this disease, where it promotes constitutive activation of gluconeogenesis and fatty acid oxidation through its association with the nuclear hormone receptors HNF-4 and PPAR-alpha, respectively. |
| 1132 | 15107844 | Hepatic insulin sensitivity was enhanced in PGC-1-deficient mice, reflecting in part the reduced expression of the mammalian tribbles homolog TRB-3, a fasting-inducible inhibitor of the serine-threonine kinase Akt/PKB (ref. 6). |
| 1133 | 15107844 | We show here that, in the liver, TRB-3 is a target for PPAR-alpha. |
| 1134 | 15107844 | Knockdown of hepatic TRB-3 expression improved glucose tolerance, whereas hepatic overexpression of TRB-3 reversed the insulin-sensitive phenotype of PGC-1-deficient mice. |
| 1135 | 15107844 | These results indicate a link between nuclear hormone receptor and insulin signaling pathways, and suggest a potential role for TRB-3 inhibitors in the treatment of type 2 diabetes. |
| 1136 | 15142986 | Selective deletion of the Hnf1beta (MODY5) gene in beta-cells leads to altered gene expression and defective insulin release. |
| 1137 | 15142986 | Hepatocyte nuclear factor 1alpha (HNF1alpha) and HNF1beta (or vHNF1) are closely related transcription factors expressed in liver, kidney, gut, and pancreatic beta-cells. |
| 1138 | 15142986 | Human mutations in HNF1alpha or HNF1beta lead to maturity-onset diabetes of the young (MODY3 and MODY5, respectively), and patients present with impaired glucose-stimulated insulin secretion. |
| 1139 | 15142986 | To examine the role of HNF1beta in glucose homeostasis, viable mice deleted for HNF1beta selectively in beta-cells (beta/H1beta-KO mice) were generated using a Cre-LoxP strategy. beta/H1beta-KO mice had normal growth, fertility, fed or fasted plasma glucose and insulin levels, pancreatic insulin content, and insulin sensitivity. |
| 1140 | 15142986 | Moreover, beta/H1beta-KO islets had increased HNF1alpha and Pdx-1, decreased HNF4 mRNA levels, and reduced glucose-stimulated insulin release. |
| 1141 | 15216446 | We have screened the GCK gene and HNF-1alpha gene by direct sequencing in three German families with early onset type-2-diabetes, possibly MODY. |
| 1142 | 15233628 | Mutations in the HNF4alpha gene correlate with MODY1 (maturity-onset diabetes of the young 1), a form of type II diabetes characterized by an impaired glucose-induced insulin secretion. |
| 1143 | 15233628 | Conversely, in pancreatic beta-cell lines, this mutation resulted in strong impairments of HNF4alpha transcriptional activity on the promoters of LPK (liver pyruvate kinase) and HNF1alpha, with this transcription factor playing a key role in endocrine pancreas. |
| 1144 | 15233628 | Mutations in the HNF4alpha gene correlate with MODY1 (maturity-onset diabetes of the young 1), a form of type II diabetes characterized by an impaired glucose-induced insulin secretion. |
| 1145 | 15233628 | Conversely, in pancreatic beta-cell lines, this mutation resulted in strong impairments of HNF4alpha transcriptional activity on the promoters of LPK (liver pyruvate kinase) and HNF1alpha, with this transcription factor playing a key role in endocrine pancreas. |
| 1146 | 15281001 | The abnormal glucose-stimulated insulin secretion in MODY1 subjects may be due to reduced glucose transport and glycolysis. |
| 1147 | 15281001 | We recruited a Philippino family with autosomal dominant early-onset type 2 diabetes and screened the proband for mutations in the genes for HNF-1alpha, GCK, HNF-4alpha, IPF-1, HNF-6, and NGN3. |
| 1148 | 15281001 | The abnormal glucose-stimulated insulin secretion in MODY1 subjects may be due to reduced glucose transport and glycolysis. |
| 1149 | 15281001 | We recruited a Philippino family with autosomal dominant early-onset type 2 diabetes and screened the proband for mutations in the genes for HNF-1alpha, GCK, HNF-4alpha, IPF-1, HNF-6, and NGN3. |
| 1150 | 15388792 | A distal region involving hepatocyte nuclear factor 4alpha and CAAT/enhancer binding protein markedly potentiates the protein kinase A stimulation of the glucose-6-phosphatase promoter. |
| 1151 | 15388792 | Using different molecular approaches, we demonstrate that hepatocyte nuclear factor (HNF4alpha), CAAT/enhancer-binding protein-alpha (C/EBPalpha), C/EBPbeta, and cAMP response element-binding protein (CREB) are involved in the potentiated PKA responsiveness: in the distal region, via one HNF4alpha- and one C/EBP-binding sites, and in the proximal region, via two HNF4alpha and two CREB-binding sites. |
| 1152 | 15388792 | We also show that HNF4alpha, C/EBPalpha, and C/EBPbeta are constitutively bound to the endogenous Glc6Pase gene, whereas CREB and CREB-binding protein (CBP) will be bound to the gene upon stimulation by cAMP. |
| 1153 | 15388792 | These data strongly suggest that the cAMP responsiveness of the Glc6Pase promoter requires a tight cooperation between a proximal and a distal region, which depends on the presence of several HNF4alpha-, C/EBP-, and CREB-binding sites, therefore involving an intricate association of hepatic and ubiquitous transcription factors. |
| 1154 | 15388792 | A distal region involving hepatocyte nuclear factor 4alpha and CAAT/enhancer binding protein markedly potentiates the protein kinase A stimulation of the glucose-6-phosphatase promoter. |
| 1155 | 15388792 | Using different molecular approaches, we demonstrate that hepatocyte nuclear factor (HNF4alpha), CAAT/enhancer-binding protein-alpha (C/EBPalpha), C/EBPbeta, and cAMP response element-binding protein (CREB) are involved in the potentiated PKA responsiveness: in the distal region, via one HNF4alpha- and one C/EBP-binding sites, and in the proximal region, via two HNF4alpha and two CREB-binding sites. |
| 1156 | 15388792 | We also show that HNF4alpha, C/EBPalpha, and C/EBPbeta are constitutively bound to the endogenous Glc6Pase gene, whereas CREB and CREB-binding protein (CBP) will be bound to the gene upon stimulation by cAMP. |
| 1157 | 15388792 | These data strongly suggest that the cAMP responsiveness of the Glc6Pase promoter requires a tight cooperation between a proximal and a distal region, which depends on the presence of several HNF4alpha-, C/EBP-, and CREB-binding sites, therefore involving an intricate association of hepatic and ubiquitous transcription factors. |
| 1158 | 15388792 | A distal region involving hepatocyte nuclear factor 4alpha and CAAT/enhancer binding protein markedly potentiates the protein kinase A stimulation of the glucose-6-phosphatase promoter. |
| 1159 | 15388792 | Using different molecular approaches, we demonstrate that hepatocyte nuclear factor (HNF4alpha), CAAT/enhancer-binding protein-alpha (C/EBPalpha), C/EBPbeta, and cAMP response element-binding protein (CREB) are involved in the potentiated PKA responsiveness: in the distal region, via one HNF4alpha- and one C/EBP-binding sites, and in the proximal region, via two HNF4alpha and two CREB-binding sites. |
| 1160 | 15388792 | We also show that HNF4alpha, C/EBPalpha, and C/EBPbeta are constitutively bound to the endogenous Glc6Pase gene, whereas CREB and CREB-binding protein (CBP) will be bound to the gene upon stimulation by cAMP. |
| 1161 | 15388792 | These data strongly suggest that the cAMP responsiveness of the Glc6Pase promoter requires a tight cooperation between a proximal and a distal region, which depends on the presence of several HNF4alpha-, C/EBP-, and CREB-binding sites, therefore involving an intricate association of hepatic and ubiquitous transcription factors. |
| 1162 | 15497766 | The role of transcription factors such as SREBP1c and nuclear receptors such as PPAR-alpha, HNF-4alpha, and LXRalpha in mediating the nuclear effects of PUFAs are addressed. |
| 1163 | 15520459 | Pattern of genes influenced by conditional expression of the transcription factors HNF6, HNF4alpha and HNF1beta in a pancreatic beta-cell line. |
| 1164 | 15520459 | Using a clone expressing the HNF6, HNF4alpha and HNF1beta transcription factors at a limited level, we introduced the expression vectors encoding these factors. |
| 1165 | 15520459 | Pattern of genes influenced by conditional expression of the transcription factors HNF6, HNF4alpha and HNF1beta in a pancreatic beta-cell line. |
| 1166 | 15520459 | Using a clone expressing the HNF6, HNF4alpha and HNF1beta transcription factors at a limited level, we introduced the expression vectors encoding these factors. |
| 1167 | 15522234 | Effect of mutations in HNF-1alpha and HNF-1beta on the transcriptional regulation of human sucrase-isomaltase in Caco-2 cells. |
| 1168 | 15522234 | Mutations in transcription factors hepatocyte nuclear factors (HNF)-1alpha and HNF-1beta cause maturity-onset diabetes of the young (MODY) types 3 and 5, respectively. |
| 1169 | 15522234 | HNF-1alpha and HNF-1beta mutations are well studied in some tissues, but the mechanism by which HNF-1alpha and HNF-1beta mutations affect sucrase-isomaltase (SI) transcription in the small intestine is unclear. |
| 1170 | 15522234 | We studied the effects of 13 HNF-1alpha mutants and 2 HNF-1beta mutants on human SI gene transcription, which were identified in subjects with MODY3 and MODY5, respectively. |
| 1171 | 15522234 | Transactivation activity of 11 HNF-1alpha and 2 HNF-1beta mutants was significantly lower than that of wild (wt)-HNF-1alpha and wt-HNF-1beta. |
| 1172 | 15522234 | These results suggest that SI transcription might tend to be unchanged or lower in MODY3, while occurring more in MODY5. |
| 1173 | 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. |
| 1174 | 15591035 | Transcriptional regulation of glucose-6-phosphatase catalytic subunit promoter by insulin and glucose in the carnivorous fish, Sparus aurata. |
| 1175 | 15591035 | Increase in glucose-6-phosphatase catalytic subunit (G6Pase, G6pc) transcription enhances hepatic glucose production in non-insulin-dependent diabetes mellitus (NIDDM). |
| 1176 | 15591035 | Transfection experiments in HepG2 cells showed that insulin repressed S. aurata G6pc under high-glucose conditions. |
| 1177 | 15591035 | Synergistic activation of piscine G6pc promoter was induced by cotransfection with expression plasmids for hepatocyte nuclear factor-4alpha (HNF-4alpha) and peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1alpha). |
| 1178 | 15591035 | No direct relationship was found between PGC-1alpha coactivation of HNF-4alpha transactivation and the repressive effect of insulin. |
| 1179 | 15591035 | Interestingly, insulin hardly affected G6pc promoter activity in the absence of glucose, suggesting that a reduced capacity of insulin-dependent repression of piscine G6pc may lead to insulin resistance in carnivorous fish. |
| 1180 | 15591035 | Transcriptional regulation of glucose-6-phosphatase catalytic subunit promoter by insulin and glucose in the carnivorous fish, Sparus aurata. |
| 1181 | 15591035 | Increase in glucose-6-phosphatase catalytic subunit (G6Pase, G6pc) transcription enhances hepatic glucose production in non-insulin-dependent diabetes mellitus (NIDDM). |
| 1182 | 15591035 | Transfection experiments in HepG2 cells showed that insulin repressed S. aurata G6pc under high-glucose conditions. |
| 1183 | 15591035 | Synergistic activation of piscine G6pc promoter was induced by cotransfection with expression plasmids for hepatocyte nuclear factor-4alpha (HNF-4alpha) and peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1alpha). |
| 1184 | 15591035 | No direct relationship was found between PGC-1alpha coactivation of HNF-4alpha transactivation and the repressive effect of insulin. |
| 1185 | 15591035 | Interestingly, insulin hardly affected G6pc promoter activity in the absence of glucose, suggesting that a reduced capacity of insulin-dependent repression of piscine G6pc may lead to insulin resistance in carnivorous fish. |
| 1186 | 15649097 | By far MODY2 (due to mutations of the glucokinase gene) and MODY3 (due to mutations in hepatocyte nuclear factor-1alpha) are the most frequent. |
| 1187 | 15649097 | As with MODY3, all the other MODY subtypes are associated with mutations in transcription factors. |
| 1188 | 15649097 | The clinical presentations of the different MODY subtypes differ, particularly in the severity and the course of the insulin secretion defect, the risk of microvascular complications of diabetes, and the defects associated with diabetes. |
| 1189 | 15649097 | Despite the progression of insulin defects, sensitivity to sulfonylureas may be retained in MODY3 patients. |
| 1190 | 15649097 | By far MODY2 (due to mutations of the glucokinase gene) and MODY3 (due to mutations in hepatocyte nuclear factor-1alpha) are the most frequent. |
| 1191 | 15649097 | As with MODY3, all the other MODY subtypes are associated with mutations in transcription factors. |
| 1192 | 15649097 | The clinical presentations of the different MODY subtypes differ, particularly in the severity and the course of the insulin secretion defect, the risk of microvascular complications of diabetes, and the defects associated with diabetes. |
| 1193 | 15649097 | Despite the progression of insulin defects, sensitivity to sulfonylureas may be retained in MODY3 patients. |
| 1194 | 15649945 | The seminal observation of an ovarian carcinoma in a MODY5 patient who subsequently developed a chromophobe renal cell carcinoma, prompted us to screen for HNF1beta and HNF1alpha inactivation in a series of 20 ovarian and 35 renal neoplasms. |
| 1195 | 15649945 | In these cases, the expression of PKHD1 (polycystic kidney and hepatic disease 1) and UMOD (Uromodulin), two genes regulated by HNF1beta, was turned off. |
| 1196 | 15649945 | We identified two related clusters of co-regulated genes associating HNF1beta, PKHD1 and UMOD in the first group and HNF1alpha, HNF4alpha, FABP1 and UGT2B7 in the second group. |
| 1197 | 15649945 | Finally, these results suggest that germline mutations of HNF1beta and HNF1alpha may predispose to renal tumors. |
| 1198 | 15649945 | Furthermore, we suggest that HNF1beta functions as a tumor suppressor gene in chromophobe renal cell carcinogenesis through a PKHD1 expression control. |
| 1199 | 15651981 | Deletion and chromatin immunoprecipitation analysis indicated that negative autoregulation by HNF-4alpha1 was mediated by its association with the TATA-less HNF-4alpha core promoter enriched in Sp1, but lacking DR-1 response elements. |
| 1200 | 15651981 | Also, negative autoregulation by HNF-4alpha1 was independent of its transactivation function, being similarly exerted by transcriptional-defective MODY-1 missense mutants of HNF-4alpha1, or under conditions of suppressing or enhancing HNF-4alpha activity by small heterodimer partner or by inhibiting histone deacetylase respectively. |
| 1201 | 15651981 | Deletion and chromatin immunoprecipitation analysis indicated that negative autoregulation by HNF-4alpha1 was mediated by its association with the TATA-less HNF-4alpha core promoter enriched in Sp1, but lacking DR-1 response elements. |
| 1202 | 15651981 | Also, negative autoregulation by HNF-4alpha1 was independent of its transactivation function, being similarly exerted by transcriptional-defective MODY-1 missense mutants of HNF-4alpha1, or under conditions of suppressing or enhancing HNF-4alpha activity by small heterodimer partner or by inhibiting histone deacetylase respectively. |
| 1203 | 15657605 | In Caucasians, maturity-onset diabetes of the young (MODY) is mostly caused by mutations in the hepatocyte nuclear factor (HNF)-1alpha (MODY3) and glucokinase (MODY2) genes. |
| 1204 | 15657605 | We screened for mutations in the HNF-4alpha (MODY1), MODY2 and MODY3 genes by direct sequencing. |
| 1205 | 15657605 | Insulin resistance index and other clinical data were compared in sex-, age- and duration-matched MODY3 and MODYX patients. |
| 1206 | 15657605 | Compared to MODY3 patients, MODYX patients had higher body mass index (P<0.02), higher insulin resistance index (P=0.001) and triglyceride level (P<0.02), lower HDL level (P=0.001) and more hypertension (P<0.05), but no significant difference in the prevalence of diabetic complications. |
| 1207 | 15657605 | In conclusion, MODY3 and MODY2 account for only 9 and 1%, respectively, of Chinese MODY. |
| 1208 | 15657605 | A majority of Chinese MODY patients are due to defects in unknown genes and appear to be characterized by insulin resistance. |
| 1209 | 15657605 | In Caucasians, maturity-onset diabetes of the young (MODY) is mostly caused by mutations in the hepatocyte nuclear factor (HNF)-1alpha (MODY3) and glucokinase (MODY2) genes. |
| 1210 | 15657605 | We screened for mutations in the HNF-4alpha (MODY1), MODY2 and MODY3 genes by direct sequencing. |
| 1211 | 15657605 | Insulin resistance index and other clinical data were compared in sex-, age- and duration-matched MODY3 and MODYX patients. |
| 1212 | 15657605 | Compared to MODY3 patients, MODYX patients had higher body mass index (P<0.02), higher insulin resistance index (P=0.001) and triglyceride level (P<0.02), lower HDL level (P=0.001) and more hypertension (P<0.05), but no significant difference in the prevalence of diabetic complications. |
| 1213 | 15657605 | In conclusion, MODY3 and MODY2 account for only 9 and 1%, respectively, of Chinese MODY. |
| 1214 | 15657605 | A majority of Chinese MODY patients are due to defects in unknown genes and appear to be characterized by insulin resistance. |
| 1215 | 15657605 | In Caucasians, maturity-onset diabetes of the young (MODY) is mostly caused by mutations in the hepatocyte nuclear factor (HNF)-1alpha (MODY3) and glucokinase (MODY2) genes. |
| 1216 | 15657605 | We screened for mutations in the HNF-4alpha (MODY1), MODY2 and MODY3 genes by direct sequencing. |
| 1217 | 15657605 | Insulin resistance index and other clinical data were compared in sex-, age- and duration-matched MODY3 and MODYX patients. |
| 1218 | 15657605 | Compared to MODY3 patients, MODYX patients had higher body mass index (P<0.02), higher insulin resistance index (P=0.001) and triglyceride level (P<0.02), lower HDL level (P=0.001) and more hypertension (P<0.05), but no significant difference in the prevalence of diabetic complications. |
| 1219 | 15657605 | In conclusion, MODY3 and MODY2 account for only 9 and 1%, respectively, of Chinese MODY. |
| 1220 | 15657605 | A majority of Chinese MODY patients are due to defects in unknown genes and appear to be characterized by insulin resistance. |
| 1221 | 15657605 | In Caucasians, maturity-onset diabetes of the young (MODY) is mostly caused by mutations in the hepatocyte nuclear factor (HNF)-1alpha (MODY3) and glucokinase (MODY2) genes. |
| 1222 | 15657605 | We screened for mutations in the HNF-4alpha (MODY1), MODY2 and MODY3 genes by direct sequencing. |
| 1223 | 15657605 | Insulin resistance index and other clinical data were compared in sex-, age- and duration-matched MODY3 and MODYX patients. |
| 1224 | 15657605 | Compared to MODY3 patients, MODYX patients had higher body mass index (P<0.02), higher insulin resistance index (P=0.001) and triglyceride level (P<0.02), lower HDL level (P=0.001) and more hypertension (P<0.05), but no significant difference in the prevalence of diabetic complications. |
| 1225 | 15657605 | In conclusion, MODY3 and MODY2 account for only 9 and 1%, respectively, of Chinese MODY. |
| 1226 | 15657605 | A majority of Chinese MODY patients are due to defects in unknown genes and appear to be characterized by insulin resistance. |
| 1227 | 15711583 | In mammals, one of the most characterized examples of regulation of metabolic pathways by transcriptional coactivators is peroxisome proliferator-activated receptors gamma (PPARgamma) coactivator-1 alpha (PGC-1alpha). |
| 1228 | 15711583 | These transcription factors can be ubiquitous such as the nuclear respiratory factors or tissue-enriched factors such as PPARgamma (brown fat), hepatocyte nuclear factor (HNF4alpha) (liver and pancreas) and muscle enhancer factor (MEF2s). |
| 1229 | 15711641 | Complementary roles of IRS-1 and IRS-2 in the hepatic regulation of metabolism. |
| 1230 | 15711641 | In many cases, insulin resistance in liver is associated with reduced expression of both major insulin receptor substrate (IRS) proteins, IRS-1 and IRS-2. |
| 1231 | 15711641 | To investigate the specific functions of IRS-1 and IRS-2 in regulating liver function in vivo, we developed an adenovirus-mediated RNA interference technique in which short hairpin RNAs (shRNAs) are used to knock down IRS-1, IRS-2, or both, by 70-80% in livers of WT mice. |
| 1232 | 15711641 | The knockdown of IRS-1 resulted in an upregulation of the gluconeogenic enzymes glucose-6 phosphatase and phosphoenolpyruvate carboxykinase, as well as a marked increase in hepatic nuclear factor-4 alpha. |
| 1233 | 15711641 | Decreased IRS-1 was also associated with a decrease in glucokinase expression and a trend toward increased blood glucose, whereas knockdown of IRS-2 resulted in the upregulation of lipogenic enzymes SREBP-1c and fatty acid synthase, as well as increased hepatic lipid accumulation. |
| 1234 | 15711641 | The concomitant injection of IRS-1 and IRS-2 adenoviral shRNAs resulted in systemic insulin resistance, glucose intolerance, and hepatic steatosis. |
| 1235 | 15711641 | Taken together, our results demonstrate that hepatic IRS-1 and IRS-2 have complementary roles in the control of hepatic metabolism, with IRS-1 more closely linked to glucose homeostasis and IRS-2 more closely linked to lipid metabolism. |
| 1236 | 15715885 | Monogenic forms of diabetes (maturity-onset diabetes of the young, MODY) have been identified and classified into MODY1-6 according to the mutated genes that by being expressed in the pancreatic beta-cells confirm at the molecular level the clinical presentation of MODY as a predominantly insulin secretory deficient form of diabetes mellitus. |
| 1237 | 15715885 | Mutation analyses of selected 'candidate' susceptibility genes in various populations have also identified the widespread Pro12Ala variant of the peroxisome proliferator-activated receptor-gamma and the common Glu23Lys variant of the ATP-sensitive potassium channel, Kir6.2 (KCNJ11). |
| 1238 | 15719061 | Mammalian nuclear hormone receptors (NHRs), such as liver X receptor, farnesoid X receptor, and peroxisome proliferator-activated receptors (PPARs), precisely control energy metabolism. |
| 1239 | 15719061 | Despite its sequence relationship with the mammalian hepatocyte nuclear factor 4 receptor, the biological activities of nhr-49 were most similar to those of the mammalian PPARs, implying an evolutionarily conserved role for NHRs in modulating fat consumption and composition. |
| 1240 | 15728204 | HNF4A encodes an orphan nuclear receptor that plays crucial roles in regulating hepatic gluconeogenesis and insulin secretion. |
| 1241 | 15752752 | Mutations in the hepatocyte nuclear factor (HNF) 4alpha gene cause a form of maturity-onset diabetes of the young (MODY1), which is a monogenic form of type 2 diabetes characterized by impaired insulin secretion by pancreatic beta-cells. |
| 1242 | 15754742 | In addition to MODY, IPF-1 mutations are suggested to predispose to common late-onset T2DM with different penetration of the mutations reflected in their in vitro activity. |
| 1243 | 15761495 | The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretion. |
| 1244 | 15761495 | These phenotypes can be explained in part by a 60% reduction in expression of the potassium channel subunit Kir6.2. |
| 1245 | 15761495 | We demonstrate using cotransfection assays that the Kir6.2 gene is a transcriptional target of HNF-4alpha. |
| 1246 | 15761495 | Our data provide genetic evidence that HNF-4alpha is required in the pancreatic beta cell for regulation of the pathway of insulin secretion dependent on the ATP-dependent potassium channel. |
| 1247 | 15761495 | The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretion. |
| 1248 | 15761495 | These phenotypes can be explained in part by a 60% reduction in expression of the potassium channel subunit Kir6.2. |
| 1249 | 15761495 | We demonstrate using cotransfection assays that the Kir6.2 gene is a transcriptional target of HNF-4alpha. |
| 1250 | 15761495 | Our data provide genetic evidence that HNF-4alpha is required in the pancreatic beta cell for regulation of the pathway of insulin secretion dependent on the ATP-dependent potassium channel. |
| 1251 | 15761495 | The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretion. |
| 1252 | 15761495 | These phenotypes can be explained in part by a 60% reduction in expression of the potassium channel subunit Kir6.2. |
| 1253 | 15761495 | We demonstrate using cotransfection assays that the Kir6.2 gene is a transcriptional target of HNF-4alpha. |
| 1254 | 15761495 | Our data provide genetic evidence that HNF-4alpha is required in the pancreatic beta cell for regulation of the pathway of insulin secretion dependent on the ATP-dependent potassium channel. |
| 1255 | 15841481 | Identification of novel GCK and HNF1A/TCF1 mutations and polymorphisms in German families with maturity-onset diabetes of the young (MODY). |
| 1256 | 15841481 | Forty families with a clinical presentation suggestive of MODY were screened for the most common MODY subtypes caused by mutations in the genes encoding glucokinase (GCK, MODY2) and hepatocyte nuclear 1-alpha (HNF1A/TCF1, MODY3). |
| 1257 | 15841481 | Identification of novel GCK and HNF1A/TCF1 mutations and polymorphisms in German families with maturity-onset diabetes of the young (MODY). |
| 1258 | 15841481 | Forty families with a clinical presentation suggestive of MODY were screened for the most common MODY subtypes caused by mutations in the genes encoding glucokinase (GCK, MODY2) and hepatocyte nuclear 1-alpha (HNF1A/TCF1, MODY3). |
| 1259 | 15928245 | Half of clinically defined maturity-onset diabetes of the young patients in Denmark do not have mutations in HNF4A, GCK, and TCF1. |
| 1260 | 15955117 | MODY is a group of six different forms of monogenic diabetes, characterized by insulin secretion defects in pancreatic beta-cells, supposed to be responsible for 2-5% of all cases of diabetes. |
| 1261 | 15955369 | The majority of proteins associated with MODY are transcription factors, such as hepatocyte nuclear factor 4alpha (HNF-4alpha), HNF-1alpha, insulin promoter factor-1 (IPF-1), HNF-1beta, and NEUROD1. |
| 1262 | 15955369 | In addition, some evidence exists that genes, such as adiponectin, IRS-1, and some others may also influence the susceptibility to T2DM. |
| 1263 | 15967803 | Cloning of the rat pyruvate dehydrogenase kinase 4 gene promoter: activation of pyruvate dehydrogenase kinase 4 by the peroxisome proliferator-activated receptor gamma coactivator. |
| 1264 | 15967803 | The pyruvate dehydrogenase complex catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the metabolism of glucose to acetyl-CoA. |
| 1265 | 15967803 | Phosphorylation of pyruvate dehydrogenase by the pyruvate dehydrogenase kinases (PDK) inhibits pyruvate dehydrogenase complex activity. |
| 1266 | 15967803 | There are four PDK isoforms, and expression of PDK4 and PDK2 genes is elevated in starvation and diabetes, allowing glucose to be conserved while fatty acid oxidation is increased. |
| 1267 | 15967803 | The peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of genes involved in hepatic gluconeogenesis and mitochondrial fatty acid oxidation. |
| 1268 | 15967803 | We have found that PGC-1alpha will induce the expression of both the PDK2 and PDK4 genes in primary rat hepatocytes and ventricular myocytes. |
| 1269 | 15967803 | Hepatic nuclear factor 4 (HNF4), which activates many genes in the liver, will induce PDK4 expression. |
| 1270 | 15967803 | Although HNF4 and PGC-1alpha interact to stimulate several genes encoding gluconeogenic enzymes, the induction of PDK4 does not involve interactions of PGC-1alpha with HNF4. |
| 1271 | 15967803 | Using the chromatin immunoprecipitation assay, we have demonstrated that HNF4 and PGC-1alpha are associated with the PDK4 gene in vivo. |
| 1272 | 15967803 | Cloning of the rat pyruvate dehydrogenase kinase 4 gene promoter: activation of pyruvate dehydrogenase kinase 4 by the peroxisome proliferator-activated receptor gamma coactivator. |
| 1273 | 15967803 | The pyruvate dehydrogenase complex catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the metabolism of glucose to acetyl-CoA. |
| 1274 | 15967803 | Phosphorylation of pyruvate dehydrogenase by the pyruvate dehydrogenase kinases (PDK) inhibits pyruvate dehydrogenase complex activity. |
| 1275 | 15967803 | There are four PDK isoforms, and expression of PDK4 and PDK2 genes is elevated in starvation and diabetes, allowing glucose to be conserved while fatty acid oxidation is increased. |
| 1276 | 15967803 | The peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of genes involved in hepatic gluconeogenesis and mitochondrial fatty acid oxidation. |
| 1277 | 15967803 | We have found that PGC-1alpha will induce the expression of both the PDK2 and PDK4 genes in primary rat hepatocytes and ventricular myocytes. |
| 1278 | 15967803 | Hepatic nuclear factor 4 (HNF4), which activates many genes in the liver, will induce PDK4 expression. |
| 1279 | 15967803 | Although HNF4 and PGC-1alpha interact to stimulate several genes encoding gluconeogenic enzymes, the induction of PDK4 does not involve interactions of PGC-1alpha with HNF4. |
| 1280 | 15967803 | Using the chromatin immunoprecipitation assay, we have demonstrated that HNF4 and PGC-1alpha are associated with the PDK4 gene in vivo. |
| 1281 | 15967803 | Cloning of the rat pyruvate dehydrogenase kinase 4 gene promoter: activation of pyruvate dehydrogenase kinase 4 by the peroxisome proliferator-activated receptor gamma coactivator. |
| 1282 | 15967803 | The pyruvate dehydrogenase complex catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the metabolism of glucose to acetyl-CoA. |
| 1283 | 15967803 | Phosphorylation of pyruvate dehydrogenase by the pyruvate dehydrogenase kinases (PDK) inhibits pyruvate dehydrogenase complex activity. |
| 1284 | 15967803 | There are four PDK isoforms, and expression of PDK4 and PDK2 genes is elevated in starvation and diabetes, allowing glucose to be conserved while fatty acid oxidation is increased. |
| 1285 | 15967803 | The peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of genes involved in hepatic gluconeogenesis and mitochondrial fatty acid oxidation. |
| 1286 | 15967803 | We have found that PGC-1alpha will induce the expression of both the PDK2 and PDK4 genes in primary rat hepatocytes and ventricular myocytes. |
| 1287 | 15967803 | Hepatic nuclear factor 4 (HNF4), which activates many genes in the liver, will induce PDK4 expression. |
| 1288 | 15967803 | Although HNF4 and PGC-1alpha interact to stimulate several genes encoding gluconeogenic enzymes, the induction of PDK4 does not involve interactions of PGC-1alpha with HNF4. |
| 1289 | 15967803 | Using the chromatin immunoprecipitation assay, we have demonstrated that HNF4 and PGC-1alpha are associated with the PDK4 gene in vivo. |
| 1290 | 15983230 | The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in the genes regulating insulin secretion (SLC2A2 [encoding GLUT2], GCK, TCF1 [encoding HNF-1alpha], HNF4A, GIP, and GLP1R) are associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in participants of the Finnish Diabetes Prevention Study. |
| 1291 | 16035308 | Six genetic mutations have been described, one of them affecting the glucokinase gene (MODY 2) and the others various transcription factors HNF-1alpha, HNF-4alpha, HNF-1beta, IPF-1 and NeuroD (MODY 1,3,4,5,6, respectively). |
| 1292 | 16035308 | Among the two most frequent forms, MODY 2 (mutation of the glucokinase gene) has a benign clinical evolution whereas MODY 3 (mutation of HNF-1alpha gene) has a much more severe evolution. |
| 1293 | 16035391 | The hepatic nuclear factor 4alpha (HNF4alpha) gene partly explains the linkage peak on chromosome 20, while the upstream transcription factor (USF1) is associated with familial combined hyperlipidaemia (FCHL) and maps close to the type 2 diabetes associated 1q peak. |
| 1294 | 16035391 | Many genes accounting for monogenic forms of diabetes have been identified--such as maturity onset diabetes of the young (MODY); glucokinase (GCK) and HNF1alpha mutations being the most common causes of MODY. |
| 1295 | 16035391 | GCK variants result in 'mild' diabetes or impaired glucose tolerance (IGT) and relatively few cardiovascular complications, while HNF1alpha-associated MODY is more typical of type 2 diabetes, frequently being treated with sulphonylureas or insulin and resulting in microvascular complications. |
| 1296 | 16059790 | Genetic testing for glucokinase mutations in clinically selected patients with MODY: a worthwhile investment. |
| 1297 | 16059790 | The most common subtypes are caused by mutations in the genes encoding the transcription factor HNF-1a (MODY 3) and the glycolytic enzyme glucokinase (GCK) (MODY 2). |
| 1298 | 16059790 | The five-year-old girl was started on insulin therapy for her diabetes but because her HbA1c remained between 5.8-6.4% (reference 4.1-5.7%) and her clinical presentation suggested MODY insulin was discontinued. |
| 1299 | 16059790 | Genetic testing for glucokinase mutations in clinically selected patients with MODY: a worthwhile investment. |
| 1300 | 16059790 | The most common subtypes are caused by mutations in the genes encoding the transcription factor HNF-1a (MODY 3) and the glycolytic enzyme glucokinase (GCK) (MODY 2). |
| 1301 | 16059790 | The five-year-old girl was started on insulin therapy for her diabetes but because her HbA1c remained between 5.8-6.4% (reference 4.1-5.7%) and her clinical presentation suggested MODY insulin was discontinued. |
| 1302 | 16059790 | Genetic testing for glucokinase mutations in clinically selected patients with MODY: a worthwhile investment. |
| 1303 | 16059790 | The most common subtypes are caused by mutations in the genes encoding the transcription factor HNF-1a (MODY 3) and the glycolytic enzyme glucokinase (GCK) (MODY 2). |
| 1304 | 16059790 | The five-year-old girl was started on insulin therapy for her diabetes but because her HbA1c remained between 5.8-6.4% (reference 4.1-5.7%) and her clinical presentation suggested MODY insulin was discontinued. |
| 1305 | 16096055 | Using oligonucleotide microarrays and real-time PCR of pancreatic islets isolated from humans with type 2 diabetes versus normal glucose-tolerant controls, we identified multiple changes in expression of genes known to be important in beta cell function, including major decreases in expression of HNF4alpha, insulin receptor, IRS2, Akt2, and several glucose-metabolic-pathway genes. |
| 1306 | 16223942 | Mechanisms of mutual functional interactions between HNF-4alpha and HNF-1alpha revealed by mutations that cause maturity onset diabetes of the young. |
| 1307 | 16223942 | HNF-4alpha and HNF-1alpha cooperatively activate genes with binding sites for both factors, whereas suppressive interactions occur at regulatory sequences with a binding site for only one factor. |
| 1308 | 16223942 | The liver fatty acid binding protein gene (Fabp1) has binding sites for both factors, and chromatin precipitation assays were utilized to demonstrate that HNF-4alpha increased HNF-1alpha Fabp1 promoter occupancy during cooperative transcriptional activation. |
| 1309 | 16223942 | The HNF4 P2 promoter contains a HNF-1 but not HNF-4 binding site, and HNF-4alpha suppressed HNF-1alpha HNF4 P2 activation and decreased promoter HNF-1alpha occupancy. |
| 1310 | 16223942 | The apolipoprotein C III (APOC3) promoter contains a HNF-4 but not HNF-1 binding site, and HNF-1alpha suppressed HNF-4alpha APOC3 activation and decreased HNF-4alpha promoter occupancy. |
| 1311 | 16223942 | Maturity onset diabetes of the young (MODY) as well as defects in hepatic lipid metabolism result from mutations in either HNF-4alpha or HNF-1alpha. |
| 1312 | 16223942 | We found that MODY missense mutant R127W HNF-4alpha retained wild-type individual Fabp1 activation and bound to HNF-1alpha better than wild-type HNF-4alpha, yet did not cooperate with HNF-1alpha or increase HNF-1alpha Fabp1 promoter occupancy. |
| 1313 | 16223942 | The HNF-1alpha R131Q MODY mutant also retained wild-type Fabp1 activation and bound to HNF-4alpha as well as the wild type but was defective in both suppressing HNF-4alpha APOC3 activation and decreasing HNF-4alpha promoter occupancy. |
| 1314 | 16223942 | Mechanisms of mutual functional interactions between HNF-4alpha and HNF-1alpha revealed by mutations that cause maturity onset diabetes of the young. |
| 1315 | 16223942 | HNF-4alpha and HNF-1alpha cooperatively activate genes with binding sites for both factors, whereas suppressive interactions occur at regulatory sequences with a binding site for only one factor. |
| 1316 | 16223942 | The liver fatty acid binding protein gene (Fabp1) has binding sites for both factors, and chromatin precipitation assays were utilized to demonstrate that HNF-4alpha increased HNF-1alpha Fabp1 promoter occupancy during cooperative transcriptional activation. |
| 1317 | 16223942 | The HNF4 P2 promoter contains a HNF-1 but not HNF-4 binding site, and HNF-4alpha suppressed HNF-1alpha HNF4 P2 activation and decreased promoter HNF-1alpha occupancy. |
| 1318 | 16223942 | The apolipoprotein C III (APOC3) promoter contains a HNF-4 but not HNF-1 binding site, and HNF-1alpha suppressed HNF-4alpha APOC3 activation and decreased HNF-4alpha promoter occupancy. |
| 1319 | 16223942 | Maturity onset diabetes of the young (MODY) as well as defects in hepatic lipid metabolism result from mutations in either HNF-4alpha or HNF-1alpha. |
| 1320 | 16223942 | We found that MODY missense mutant R127W HNF-4alpha retained wild-type individual Fabp1 activation and bound to HNF-1alpha better than wild-type HNF-4alpha, yet did not cooperate with HNF-1alpha or increase HNF-1alpha Fabp1 promoter occupancy. |
| 1321 | 16223942 | The HNF-1alpha R131Q MODY mutant also retained wild-type Fabp1 activation and bound to HNF-4alpha as well as the wild type but was defective in both suppressing HNF-4alpha APOC3 activation and decreasing HNF-4alpha promoter occupancy. |
| 1322 | 16223942 | Mechanisms of mutual functional interactions between HNF-4alpha and HNF-1alpha revealed by mutations that cause maturity onset diabetes of the young. |
| 1323 | 16223942 | HNF-4alpha and HNF-1alpha cooperatively activate genes with binding sites for both factors, whereas suppressive interactions occur at regulatory sequences with a binding site for only one factor. |
| 1324 | 16223942 | The liver fatty acid binding protein gene (Fabp1) has binding sites for both factors, and chromatin precipitation assays were utilized to demonstrate that HNF-4alpha increased HNF-1alpha Fabp1 promoter occupancy during cooperative transcriptional activation. |
| 1325 | 16223942 | The HNF4 P2 promoter contains a HNF-1 but not HNF-4 binding site, and HNF-4alpha suppressed HNF-1alpha HNF4 P2 activation and decreased promoter HNF-1alpha occupancy. |
| 1326 | 16223942 | The apolipoprotein C III (APOC3) promoter contains a HNF-4 but not HNF-1 binding site, and HNF-1alpha suppressed HNF-4alpha APOC3 activation and decreased HNF-4alpha promoter occupancy. |
| 1327 | 16223942 | Maturity onset diabetes of the young (MODY) as well as defects in hepatic lipid metabolism result from mutations in either HNF-4alpha or HNF-1alpha. |
| 1328 | 16223942 | We found that MODY missense mutant R127W HNF-4alpha retained wild-type individual Fabp1 activation and bound to HNF-1alpha better than wild-type HNF-4alpha, yet did not cooperate with HNF-1alpha or increase HNF-1alpha Fabp1 promoter occupancy. |
| 1329 | 16223942 | The HNF-1alpha R131Q MODY mutant also retained wild-type Fabp1 activation and bound to HNF-4alpha as well as the wild type but was defective in both suppressing HNF-4alpha APOC3 activation and decreasing HNF-4alpha promoter occupancy. |
| 1330 | 16223942 | Mechanisms of mutual functional interactions between HNF-4alpha and HNF-1alpha revealed by mutations that cause maturity onset diabetes of the young. |
| 1331 | 16223942 | HNF-4alpha and HNF-1alpha cooperatively activate genes with binding sites for both factors, whereas suppressive interactions occur at regulatory sequences with a binding site for only one factor. |
| 1332 | 16223942 | The liver fatty acid binding protein gene (Fabp1) has binding sites for both factors, and chromatin precipitation assays were utilized to demonstrate that HNF-4alpha increased HNF-1alpha Fabp1 promoter occupancy during cooperative transcriptional activation. |
| 1333 | 16223942 | The HNF4 P2 promoter contains a HNF-1 but not HNF-4 binding site, and HNF-4alpha suppressed HNF-1alpha HNF4 P2 activation and decreased promoter HNF-1alpha occupancy. |
| 1334 | 16223942 | The apolipoprotein C III (APOC3) promoter contains a HNF-4 but not HNF-1 binding site, and HNF-1alpha suppressed HNF-4alpha APOC3 activation and decreased HNF-4alpha promoter occupancy. |
| 1335 | 16223942 | Maturity onset diabetes of the young (MODY) as well as defects in hepatic lipid metabolism result from mutations in either HNF-4alpha or HNF-1alpha. |
| 1336 | 16223942 | We found that MODY missense mutant R127W HNF-4alpha retained wild-type individual Fabp1 activation and bound to HNF-1alpha better than wild-type HNF-4alpha, yet did not cooperate with HNF-1alpha or increase HNF-1alpha Fabp1 promoter occupancy. |
| 1337 | 16223942 | The HNF-1alpha R131Q MODY mutant also retained wild-type Fabp1 activation and bound to HNF-4alpha as well as the wild type but was defective in both suppressing HNF-4alpha APOC3 activation and decreasing HNF-4alpha promoter occupancy. |
| 1338 | 16223942 | Mechanisms of mutual functional interactions between HNF-4alpha and HNF-1alpha revealed by mutations that cause maturity onset diabetes of the young. |
| 1339 | 16223942 | HNF-4alpha and HNF-1alpha cooperatively activate genes with binding sites for both factors, whereas suppressive interactions occur at regulatory sequences with a binding site for only one factor. |
| 1340 | 16223942 | The liver fatty acid binding protein gene (Fabp1) has binding sites for both factors, and chromatin precipitation assays were utilized to demonstrate that HNF-4alpha increased HNF-1alpha Fabp1 promoter occupancy during cooperative transcriptional activation. |
| 1341 | 16223942 | The HNF4 P2 promoter contains a HNF-1 but not HNF-4 binding site, and HNF-4alpha suppressed HNF-1alpha HNF4 P2 activation and decreased promoter HNF-1alpha occupancy. |
| 1342 | 16223942 | The apolipoprotein C III (APOC3) promoter contains a HNF-4 but not HNF-1 binding site, and HNF-1alpha suppressed HNF-4alpha APOC3 activation and decreased HNF-4alpha promoter occupancy. |
| 1343 | 16223942 | Maturity onset diabetes of the young (MODY) as well as defects in hepatic lipid metabolism result from mutations in either HNF-4alpha or HNF-1alpha. |
| 1344 | 16223942 | We found that MODY missense mutant R127W HNF-4alpha retained wild-type individual Fabp1 activation and bound to HNF-1alpha better than wild-type HNF-4alpha, yet did not cooperate with HNF-1alpha or increase HNF-1alpha Fabp1 promoter occupancy. |
| 1345 | 16223942 | The HNF-1alpha R131Q MODY mutant also retained wild-type Fabp1 activation and bound to HNF-4alpha as well as the wild type but was defective in both suppressing HNF-4alpha APOC3 activation and decreasing HNF-4alpha promoter occupancy. |
| 1346 | 16223942 | Mechanisms of mutual functional interactions between HNF-4alpha and HNF-1alpha revealed by mutations that cause maturity onset diabetes of the young. |
| 1347 | 16223942 | HNF-4alpha and HNF-1alpha cooperatively activate genes with binding sites for both factors, whereas suppressive interactions occur at regulatory sequences with a binding site for only one factor. |
| 1348 | 16223942 | The liver fatty acid binding protein gene (Fabp1) has binding sites for both factors, and chromatin precipitation assays were utilized to demonstrate that HNF-4alpha increased HNF-1alpha Fabp1 promoter occupancy during cooperative transcriptional activation. |
| 1349 | 16223942 | The HNF4 P2 promoter contains a HNF-1 but not HNF-4 binding site, and HNF-4alpha suppressed HNF-1alpha HNF4 P2 activation and decreased promoter HNF-1alpha occupancy. |
| 1350 | 16223942 | The apolipoprotein C III (APOC3) promoter contains a HNF-4 but not HNF-1 binding site, and HNF-1alpha suppressed HNF-4alpha APOC3 activation and decreased HNF-4alpha promoter occupancy. |
| 1351 | 16223942 | Maturity onset diabetes of the young (MODY) as well as defects in hepatic lipid metabolism result from mutations in either HNF-4alpha or HNF-1alpha. |
| 1352 | 16223942 | We found that MODY missense mutant R127W HNF-4alpha retained wild-type individual Fabp1 activation and bound to HNF-1alpha better than wild-type HNF-4alpha, yet did not cooperate with HNF-1alpha or increase HNF-1alpha Fabp1 promoter occupancy. |
| 1353 | 16223942 | The HNF-1alpha R131Q MODY mutant also retained wild-type Fabp1 activation and bound to HNF-4alpha as well as the wild type but was defective in both suppressing HNF-4alpha APOC3 activation and decreasing HNF-4alpha promoter occupancy. |
| 1354 | 16223942 | Mechanisms of mutual functional interactions between HNF-4alpha and HNF-1alpha revealed by mutations that cause maturity onset diabetes of the young. |
| 1355 | 16223942 | HNF-4alpha and HNF-1alpha cooperatively activate genes with binding sites for both factors, whereas suppressive interactions occur at regulatory sequences with a binding site for only one factor. |
| 1356 | 16223942 | The liver fatty acid binding protein gene (Fabp1) has binding sites for both factors, and chromatin precipitation assays were utilized to demonstrate that HNF-4alpha increased HNF-1alpha Fabp1 promoter occupancy during cooperative transcriptional activation. |
| 1357 | 16223942 | The HNF4 P2 promoter contains a HNF-1 but not HNF-4 binding site, and HNF-4alpha suppressed HNF-1alpha HNF4 P2 activation and decreased promoter HNF-1alpha occupancy. |
| 1358 | 16223942 | The apolipoprotein C III (APOC3) promoter contains a HNF-4 but not HNF-1 binding site, and HNF-1alpha suppressed HNF-4alpha APOC3 activation and decreased HNF-4alpha promoter occupancy. |
| 1359 | 16223942 | Maturity onset diabetes of the young (MODY) as well as defects in hepatic lipid metabolism result from mutations in either HNF-4alpha or HNF-1alpha. |
| 1360 | 16223942 | We found that MODY missense mutant R127W HNF-4alpha retained wild-type individual Fabp1 activation and bound to HNF-1alpha better than wild-type HNF-4alpha, yet did not cooperate with HNF-1alpha or increase HNF-1alpha Fabp1 promoter occupancy. |
| 1361 | 16223942 | The HNF-1alpha R131Q MODY mutant also retained wild-type Fabp1 activation and bound to HNF-4alpha as well as the wild type but was defective in both suppressing HNF-4alpha APOC3 activation and decreasing HNF-4alpha promoter occupancy. |
| 1362 | 16223942 | Mechanisms of mutual functional interactions between HNF-4alpha and HNF-1alpha revealed by mutations that cause maturity onset diabetes of the young. |
| 1363 | 16223942 | HNF-4alpha and HNF-1alpha cooperatively activate genes with binding sites for both factors, whereas suppressive interactions occur at regulatory sequences with a binding site for only one factor. |
| 1364 | 16223942 | The liver fatty acid binding protein gene (Fabp1) has binding sites for both factors, and chromatin precipitation assays were utilized to demonstrate that HNF-4alpha increased HNF-1alpha Fabp1 promoter occupancy during cooperative transcriptional activation. |
| 1365 | 16223942 | The HNF4 P2 promoter contains a HNF-1 but not HNF-4 binding site, and HNF-4alpha suppressed HNF-1alpha HNF4 P2 activation and decreased promoter HNF-1alpha occupancy. |
| 1366 | 16223942 | The apolipoprotein C III (APOC3) promoter contains a HNF-4 but not HNF-1 binding site, and HNF-1alpha suppressed HNF-4alpha APOC3 activation and decreased HNF-4alpha promoter occupancy. |
| 1367 | 16223942 | Maturity onset diabetes of the young (MODY) as well as defects in hepatic lipid metabolism result from mutations in either HNF-4alpha or HNF-1alpha. |
| 1368 | 16223942 | We found that MODY missense mutant R127W HNF-4alpha retained wild-type individual Fabp1 activation and bound to HNF-1alpha better than wild-type HNF-4alpha, yet did not cooperate with HNF-1alpha or increase HNF-1alpha Fabp1 promoter occupancy. |
| 1369 | 16223942 | The HNF-1alpha R131Q MODY mutant also retained wild-type Fabp1 activation and bound to HNF-4alpha as well as the wild type but was defective in both suppressing HNF-4alpha APOC3 activation and decreasing HNF-4alpha promoter occupancy. |
| 1370 | 16249435 | Maturity-onset diabetes of the young (MODY) 5 is caused by mutations in the TCF2 gene encoding the transcription factor hepatocyte nuclear factor-1beta. |
| 1371 | 16268330 | Making a diagnosis of monogenic diabetes is important as it can have a dramatic effect on the treatment a patient should receive: glucokinase MODY patients need no treatment; HNF1alpha MODY patients are very sensitive to low dose sulphonylureas; and patients with neonatal diabetes due to Kir6.2 mutations, despite being insulin dependent, can discontinue insulin and be well controlled on high dose sulphonylurea tablets. |
| 1372 | 16377800 | Mutations in the hepatocyte nuclear factor (HNF)-4alpha gene cause a form of maturity-onset diabetes of the young (MODY1) that is characterized by impairment of glucose-stimulated insulin secretion by pancreatic beta-cells. |
| 1373 | 16377800 | The betaHNF-4alphaKO mice exhibited impairment of glucose-stimulated insulin secretion, which is a characteristic of MODY1. |
| 1374 | 16377800 | Pancreatic islet morphology, beta-cell mass, and insulin content were normal in the HNF-4alpha mutant mice. |
| 1375 | 16377800 | Expression levels of Kir6.2 and SUR1 proteins in the betaHNF-4alphaKO mice were unchanged as compared with control mice. |
| 1376 | 16377800 | Mutations in the hepatocyte nuclear factor (HNF)-4alpha gene cause a form of maturity-onset diabetes of the young (MODY1) that is characterized by impairment of glucose-stimulated insulin secretion by pancreatic beta-cells. |
| 1377 | 16377800 | The betaHNF-4alphaKO mice exhibited impairment of glucose-stimulated insulin secretion, which is a characteristic of MODY1. |
| 1378 | 16377800 | Pancreatic islet morphology, beta-cell mass, and insulin content were normal in the HNF-4alpha mutant mice. |
| 1379 | 16377800 | Expression levels of Kir6.2 and SUR1 proteins in the betaHNF-4alphaKO mice were unchanged as compared with control mice. |
| 1380 | 16377800 | Mutations in the hepatocyte nuclear factor (HNF)-4alpha gene cause a form of maturity-onset diabetes of the young (MODY1) that is characterized by impairment of glucose-stimulated insulin secretion by pancreatic beta-cells. |
| 1381 | 16377800 | The betaHNF-4alphaKO mice exhibited impairment of glucose-stimulated insulin secretion, which is a characteristic of MODY1. |
| 1382 | 16377800 | Pancreatic islet morphology, beta-cell mass, and insulin content were normal in the HNF-4alpha mutant mice. |
| 1383 | 16377800 | Expression levels of Kir6.2 and SUR1 proteins in the betaHNF-4alphaKO mice were unchanged as compared with control mice. |
| 1384 | 16562587 | We analyzed 84 Japanese patients with juvenile-onset (before 18 years of age) non-obese diabetes mellitus (DM) for mutations in the genes for HNF-1alpha, HNF-4alpha and HNF-1beta. |
| 1385 | 16562587 | No mutation was identified in the HNF-4alpha and HNF-1beta genes. |
| 1386 | 16562587 | We analyzed 84 Japanese patients with juvenile-onset (before 18 years of age) non-obese diabetes mellitus (DM) for mutations in the genes for HNF-1alpha, HNF-4alpha and HNF-1beta. |
| 1387 | 16562587 | No mutation was identified in the HNF-4alpha and HNF-1beta genes. |
| 1388 | 16632067 | Maturity-onset diabetes of the young (MODY) is mostly caused by mutations of the hepatocyte nuclear factor (HNF)-1alpha (MODY3) and glucokinase (MODY2) genes in Caucasians. |
| 1389 | 16632067 | The HNF-4alpha (MODY1), glucokinase (MODY2) and HNF-1alpha (MODY3) genes were analysed by direct sequencing. |
| 1390 | 16632067 | In conclusion, the mutations in the HNF-1alpha gene and GCK account for a small proportion, about 5% and 2.5%, respectively, in Korean MODY and early onset type 2 patients. |
| 1391 | 16632067 | Maturity-onset diabetes of the young (MODY) is mostly caused by mutations of the hepatocyte nuclear factor (HNF)-1alpha (MODY3) and glucokinase (MODY2) genes in Caucasians. |
| 1392 | 16632067 | The HNF-4alpha (MODY1), glucokinase (MODY2) and HNF-1alpha (MODY3) genes were analysed by direct sequencing. |
| 1393 | 16632067 | In conclusion, the mutations in the HNF-1alpha gene and GCK account for a small proportion, about 5% and 2.5%, respectively, in Korean MODY and early onset type 2 patients. |
| 1394 | 16632067 | Maturity-onset diabetes of the young (MODY) is mostly caused by mutations of the hepatocyte nuclear factor (HNF)-1alpha (MODY3) and glucokinase (MODY2) genes in Caucasians. |
| 1395 | 16632067 | The HNF-4alpha (MODY1), glucokinase (MODY2) and HNF-1alpha (MODY3) genes were analysed by direct sequencing. |
| 1396 | 16632067 | In conclusion, the mutations in the HNF-1alpha gene and GCK account for a small proportion, about 5% and 2.5%, respectively, in Korean MODY and early onset type 2 patients. |
| 1397 | 16672224 | Casein kinase 2 Is activated and essential for Wnt/beta-catenin signaling. |
| 1398 | 16672224 | Wnt/beta-catenin signaling is essential to early development. |
| 1399 | 16672224 | Activation of Frizzled-1 by Wnts induces nuclear accumulation of beta-catenin and activation of Lef/Tcf-dependent gene expression. |
| 1400 | 16672224 | Casein kinase 2 has been shown to affect Wnt/beta-catenin signaling. |
| 1401 | 16672224 | Herein we show to the contrary that casein kinase 2 activity is rapidly and transiently increased in response to Wnt3a stimulation and is essential for Wnt/beta-catenin signaling. |
| 1402 | 16672224 | Chemical inhibition of casein kinase 2 or suppression of its expression blocks Frizzled-1 activation of Lef/Tcf-sensitive gene expression. |
| 1403 | 16672224 | Expression of a constitutively active mutant of either Galpha(q) or Galpha(o) stimulates casein kinase 2 activation and Lef/Tcf-sensitive gene expression. |
| 1404 | 16672224 | Thus, casein kinase 2 is shown to be regulated by Wnt3a and essential to stimulation of the Frizzled-1/beta-catenin/Lef-Tcf pathway. |
| 1405 | 16672224 | Casein kinase 2 Is activated and essential for Wnt/beta-catenin signaling. |
| 1406 | 16672224 | Wnt/beta-catenin signaling is essential to early development. |
| 1407 | 16672224 | Activation of Frizzled-1 by Wnts induces nuclear accumulation of beta-catenin and activation of Lef/Tcf-dependent gene expression. |
| 1408 | 16672224 | Casein kinase 2 has been shown to affect Wnt/beta-catenin signaling. |
| 1409 | 16672224 | Herein we show to the contrary that casein kinase 2 activity is rapidly and transiently increased in response to Wnt3a stimulation and is essential for Wnt/beta-catenin signaling. |
| 1410 | 16672224 | Chemical inhibition of casein kinase 2 or suppression of its expression blocks Frizzled-1 activation of Lef/Tcf-sensitive gene expression. |
| 1411 | 16672224 | Expression of a constitutively active mutant of either Galpha(q) or Galpha(o) stimulates casein kinase 2 activation and Lef/Tcf-sensitive gene expression. |
| 1412 | 16672224 | Thus, casein kinase 2 is shown to be regulated by Wnt3a and essential to stimulation of the Frizzled-1/beta-catenin/Lef-Tcf pathway. |
| 1413 | 16679742 | The nuclear receptor constitutive androstane receptor (CAR), a key transcription factor for the expression of cytochrome P450 (CYP) 2B genes, resides in the cytoplasm under untreated conditions and translocates into the nucleus upon xenobiotic exposure. |
| 1414 | 16679742 | CAR forms a multiprotein complex including heat shock protein 90 in the cytoplasm as the glucocorticoid receptor, and it is likely that protein phosphatase 2A plays a critical role in the first step of CAR nuclear translocation. |
| 1415 | 16679742 | In obese mice fed a high-fat diet, however, hepatic CYP3A levels are drastically decreased without any significant changes in the expression of nuclear receptors including the pregnane X receptor and hepatocyte nuclear factor-4, which are known to be key transcription factors in the expression of CYP3A genes. |
| 1416 | 16731861 | We sequenced the HNF4A gene of 95 MODY3-negative probands from the Norwegian MODY Registry. |
| 1417 | 16804065 | The HNF-4alpha gene (HNF4A) resides on chromosome 20q12-q13.1, which, in addition to type 2 diabetes, has also previously been linked to high triglycerides in Finnish familial combined hyperlipidemia (FCHL) families. |
| 1418 | 16837621 | Mutations in the gene encoding hepatocyte nuclear factor (HNF)1beta result in maturity-onset diabetes of the young-(MODY)5, by impairing insulin secretory responses and, possibly, by reducing beta-cell mass. |
| 1419 | 16837621 | The functional role of HNF1beta in normal beta-cells is poorly understood; therefore, in the present study, wild-type (WT) HNF1beta, or one of two naturally occurring MODY5 mutations (an activating mutation, P328L329del, or a dominant-negative form, A263insGG) were conditionally expressed in the pancreatic beta-cell line, insulin-1 (INS-1), and the functional consequences examined. |
| 1420 | 16837621 | Induction of WT HNF1beta also inhibited the insulin secretory response to nutrient stimuli, membrane depolarisation or activation of protein kinases A and C and this correlated with a significant decrease in pancrease-duodenum homeobox-1 protein levels. |
| 1421 | 16873704 | We examined the association of variants in genes encoding several transcription factors (TCF1, TCF2, HNF4A, ISL1, IPF1, NEUROG3, PAX6, NKX2-2, NKX6-1, and NEUROD1) and genes encoding the ATP-sensitive K(+) channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) with type 2 diabetes in a Japanese cohort of 2,834 subjects. |
| 1422 | 16893891 | Transcriptional regulation of the glucose-6-phosphatase gene by cAMP/vasoactive intestinal peptide in the intestine. |
| 1423 | 16893891 | Role of HNF4alpha, CREM, HNF1alpha, and C/EBPalpha. |
| 1424 | 16893891 | Similarly to the liver, the molecular mechanism of cAMP/protein kinase A regulation involves cAMP-response element-binding protein, HNF4alpha, CAAT/enhancer-binding protein, and HNF1. |
| 1425 | 16893891 | Transcriptional regulation of the glucose-6-phosphatase gene by cAMP/vasoactive intestinal peptide in the intestine. |
| 1426 | 16893891 | Role of HNF4alpha, CREM, HNF1alpha, and C/EBPalpha. |
| 1427 | 16893891 | Similarly to the liver, the molecular mechanism of cAMP/protein kinase A regulation involves cAMP-response element-binding protein, HNF4alpha, CAAT/enhancer-binding protein, and HNF1. |
| 1428 | 16917892 | Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha (HNF1A) and 4 alpha (HNF4A) in maturity-onset diabetes of the young. |
| 1429 | 16917892 | MODY is both clinically and genetically heterogeneous, with six different genes identified to date; glucokinase (GCK), hepatocyte nuclear factor-1 alpha (HNF1A, or TCF1), hepatocyte nuclear factor-4 alpha (HNF4A), insulin promoter factor-1 (IPF1 or PDX1), hepatocyte nuclear factor-1 beta (HNF1B or TCF2), and neurogenic differentiation 1 (NEUROD1). |
| 1430 | 16917892 | Mutations in the HNF1A gene are a common cause of MODY in the majority of populations studied. |
| 1431 | 16917892 | Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. |
| 1432 | 16917892 | The identification of an HNF1A or 4A gene mutation confirms a diagnosis of MODY and has important implications for clinical management. |
| 1433 | 16917892 | Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha (HNF1A) and 4 alpha (HNF4A) in maturity-onset diabetes of the young. |
| 1434 | 16917892 | MODY is both clinically and genetically heterogeneous, with six different genes identified to date; glucokinase (GCK), hepatocyte nuclear factor-1 alpha (HNF1A, or TCF1), hepatocyte nuclear factor-4 alpha (HNF4A), insulin promoter factor-1 (IPF1 or PDX1), hepatocyte nuclear factor-1 beta (HNF1B or TCF2), and neurogenic differentiation 1 (NEUROD1). |
| 1435 | 16917892 | Mutations in the HNF1A gene are a common cause of MODY in the majority of populations studied. |
| 1436 | 16917892 | Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. |
| 1437 | 16917892 | The identification of an HNF1A or 4A gene mutation confirms a diagnosis of MODY and has important implications for clinical management. |
| 1438 | 16917892 | Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha (HNF1A) and 4 alpha (HNF4A) in maturity-onset diabetes of the young. |
| 1439 | 16917892 | MODY is both clinically and genetically heterogeneous, with six different genes identified to date; glucokinase (GCK), hepatocyte nuclear factor-1 alpha (HNF1A, or TCF1), hepatocyte nuclear factor-4 alpha (HNF4A), insulin promoter factor-1 (IPF1 or PDX1), hepatocyte nuclear factor-1 beta (HNF1B or TCF2), and neurogenic differentiation 1 (NEUROD1). |
| 1440 | 16917892 | Mutations in the HNF1A gene are a common cause of MODY in the majority of populations studied. |
| 1441 | 16917892 | Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. |
| 1442 | 16917892 | The identification of an HNF1A or 4A gene mutation confirms a diagnosis of MODY and has important implications for clinical management. |
| 1443 | 16917892 | Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha (HNF1A) and 4 alpha (HNF4A) in maturity-onset diabetes of the young. |
| 1444 | 16917892 | MODY is both clinically and genetically heterogeneous, with six different genes identified to date; glucokinase (GCK), hepatocyte nuclear factor-1 alpha (HNF1A, or TCF1), hepatocyte nuclear factor-4 alpha (HNF4A), insulin promoter factor-1 (IPF1 or PDX1), hepatocyte nuclear factor-1 beta (HNF1B or TCF2), and neurogenic differentiation 1 (NEUROD1). |
| 1445 | 16917892 | Mutations in the HNF1A gene are a common cause of MODY in the majority of populations studied. |
| 1446 | 16917892 | Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. |
| 1447 | 16917892 | The identification of an HNF1A or 4A gene mutation confirms a diagnosis of MODY and has important implications for clinical management. |
| 1448 | 16917892 | Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha (HNF1A) and 4 alpha (HNF4A) in maturity-onset diabetes of the young. |
| 1449 | 16917892 | MODY is both clinically and genetically heterogeneous, with six different genes identified to date; glucokinase (GCK), hepatocyte nuclear factor-1 alpha (HNF1A, or TCF1), hepatocyte nuclear factor-4 alpha (HNF4A), insulin promoter factor-1 (IPF1 or PDX1), hepatocyte nuclear factor-1 beta (HNF1B or TCF2), and neurogenic differentiation 1 (NEUROD1). |
| 1450 | 16917892 | Mutations in the HNF1A gene are a common cause of MODY in the majority of populations studied. |
| 1451 | 16917892 | Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. |
| 1452 | 16917892 | The identification of an HNF1A or 4A gene mutation confirms a diagnosis of MODY and has important implications for clinical management. |
| 1453 | 16925503 | Mild fasting hyperglycaemia caused by heterozygous GCK mutations rarely requires pharmacological intervention, whereas patients with mutations in the genes encoding the transcription factors HNF-1alpha and HNF-4alpha respond well to low doses of sulphonylureas. |
| 1454 | 16929032 | Apolipoprotein A-IV is regulated by nutritional and metabolic stress: involvement of glucocorticoids, HNF-4 alpha, and PGC-1 alpha. |
| 1455 | 16929032 | Apolipoprotein A-IV (apoA-IV) is a 46 kDa glycoprotein that associates with triglyceride-rich and high density lipoproteins. |
| 1456 | 16929032 | Reporter gene analysis of the murine and human apoA-IV/C-III promoters revealed a conserved cooperative activation by the hepatic nuclear factor-4 alpha (HNF-4 alpha) and the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) but no evidence of a direct regulatory role for the glucocorticoid receptor. |
| 1457 | 16929032 | Consistent with these in vitro data, induction of apoA-IV in response to fasting was accompanied by increases in HNF-4 alpha and PGC-1 alpha expression and was abolished in liver-specific HNF-4 alpha-deficient mice. |
| 1458 | 16929032 | Together, these results indicate that the induction of apoA-IV expression in fasting and diabetes likely involves PGC-1 alpha-mediated coactivation of HNF-4 alpha in addition to glucocorticoid-dependent actions. |
| 1459 | 16929032 | Apolipoprotein A-IV is regulated by nutritional and metabolic stress: involvement of glucocorticoids, HNF-4 alpha, and PGC-1 alpha. |
| 1460 | 16929032 | Apolipoprotein A-IV (apoA-IV) is a 46 kDa glycoprotein that associates with triglyceride-rich and high density lipoproteins. |
| 1461 | 16929032 | Reporter gene analysis of the murine and human apoA-IV/C-III promoters revealed a conserved cooperative activation by the hepatic nuclear factor-4 alpha (HNF-4 alpha) and the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) but no evidence of a direct regulatory role for the glucocorticoid receptor. |
| 1462 | 16929032 | Consistent with these in vitro data, induction of apoA-IV in response to fasting was accompanied by increases in HNF-4 alpha and PGC-1 alpha expression and was abolished in liver-specific HNF-4 alpha-deficient mice. |
| 1463 | 16929032 | Together, these results indicate that the induction of apoA-IV expression in fasting and diabetes likely involves PGC-1 alpha-mediated coactivation of HNF-4 alpha in addition to glucocorticoid-dependent actions. |
| 1464 | 16929032 | Apolipoprotein A-IV is regulated by nutritional and metabolic stress: involvement of glucocorticoids, HNF-4 alpha, and PGC-1 alpha. |
| 1465 | 16929032 | Apolipoprotein A-IV (apoA-IV) is a 46 kDa glycoprotein that associates with triglyceride-rich and high density lipoproteins. |
| 1466 | 16929032 | Reporter gene analysis of the murine and human apoA-IV/C-III promoters revealed a conserved cooperative activation by the hepatic nuclear factor-4 alpha (HNF-4 alpha) and the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) but no evidence of a direct regulatory role for the glucocorticoid receptor. |
| 1467 | 16929032 | Consistent with these in vitro data, induction of apoA-IV in response to fasting was accompanied by increases in HNF-4 alpha and PGC-1 alpha expression and was abolished in liver-specific HNF-4 alpha-deficient mice. |
| 1468 | 16929032 | Together, these results indicate that the induction of apoA-IV expression in fasting and diabetes likely involves PGC-1 alpha-mediated coactivation of HNF-4 alpha in addition to glucocorticoid-dependent actions. |
| 1469 | 16929032 | Apolipoprotein A-IV is regulated by nutritional and metabolic stress: involvement of glucocorticoids, HNF-4 alpha, and PGC-1 alpha. |
| 1470 | 16929032 | Apolipoprotein A-IV (apoA-IV) is a 46 kDa glycoprotein that associates with triglyceride-rich and high density lipoproteins. |
| 1471 | 16929032 | Reporter gene analysis of the murine and human apoA-IV/C-III promoters revealed a conserved cooperative activation by the hepatic nuclear factor-4 alpha (HNF-4 alpha) and the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) but no evidence of a direct regulatory role for the glucocorticoid receptor. |
| 1472 | 16929032 | Consistent with these in vitro data, induction of apoA-IV in response to fasting was accompanied by increases in HNF-4 alpha and PGC-1 alpha expression and was abolished in liver-specific HNF-4 alpha-deficient mice. |
| 1473 | 16929032 | Together, these results indicate that the induction of apoA-IV expression in fasting and diabetes likely involves PGC-1 alpha-mediated coactivation of HNF-4 alpha in addition to glucocorticoid-dependent actions. |
| 1474 | 16936201 | After correcting for testing multiple correlated SNPs within a gene, we find evidence of type 2 diabetes association with SNPs in five of the six known MODY genes: GCK, HNF1A, HNF1B, NEUROD1, and HNF4A. |
| 1475 | 17022998 | Hepatocyte nuclear factor 4 alpha ligand binding and F domains mediate interaction and transcriptional synergy with the pancreatic islet LIM HD transcription factor Isl1. |
| 1476 | 17022998 | The orphan nuclear receptor HNF4alpha and the LIM homeodomain factor Isl1 are co-expressed in pancreatic beta-cells and are required for the differentiation and function of these endocrine cells. |
| 1477 | 17022998 | These transcriptional partners interact mainly through the HNF4alpha AF-1 module and the ligand binding domain, which contains the AF-2 module. |
| 1478 | 17022998 | Here, we showed that Isl1 could enhance the HNF4alpha-mediated activation of transcription of the HNF1alpha, PPARalpha and insulin I promoters. |
| 1479 | 17022998 | Isl1 interacted with the HNF4alpha AF-2 but also required the HNF4alpha carboxy-terminal F domain for optimal interaction and transcriptional synergy. |
| 1480 | 17022998 | More specifically, we found that naturally occurring HNF4alpha isoforms, differing only in their F domain, exhibited different abilities to interact and synergize with Isl1, extending the crucial transcriptional modulatory role of the HNF4alpha F domain. |
| 1481 | 17022998 | HNF4alpha interacted with both the homeodomain and the first LIM domain of Isl1. |
| 1482 | 17022998 | We found that the transcriptional synergy between HNF4alpha and Isl1 involved an increase in HNF4alpha loading on promoter. |
| 1483 | 17022998 | The effect was more pronounced on the rat insulin I promoter containing binding sites for both HNF4alpha and Isl1 than on the human HNF1alpha promoter lacking an Isl1 binding site. |
| 1484 | 17022998 | Moreover, Isl1 could mediate the recruitment of the cofactor CLIM2 resulting in a further transcriptional enhancement of the HNF1alpha promoter activity. |
| 1485 | 17022998 | Hepatocyte nuclear factor 4 alpha ligand binding and F domains mediate interaction and transcriptional synergy with the pancreatic islet LIM HD transcription factor Isl1. |
| 1486 | 17022998 | The orphan nuclear receptor HNF4alpha and the LIM homeodomain factor Isl1 are co-expressed in pancreatic beta-cells and are required for the differentiation and function of these endocrine cells. |
| 1487 | 17022998 | These transcriptional partners interact mainly through the HNF4alpha AF-1 module and the ligand binding domain, which contains the AF-2 module. |
| 1488 | 17022998 | Here, we showed that Isl1 could enhance the HNF4alpha-mediated activation of transcription of the HNF1alpha, PPARalpha and insulin I promoters. |
| 1489 | 17022998 | Isl1 interacted with the HNF4alpha AF-2 but also required the HNF4alpha carboxy-terminal F domain for optimal interaction and transcriptional synergy. |
| 1490 | 17022998 | More specifically, we found that naturally occurring HNF4alpha isoforms, differing only in their F domain, exhibited different abilities to interact and synergize with Isl1, extending the crucial transcriptional modulatory role of the HNF4alpha F domain. |
| 1491 | 17022998 | HNF4alpha interacted with both the homeodomain and the first LIM domain of Isl1. |
| 1492 | 17022998 | We found that the transcriptional synergy between HNF4alpha and Isl1 involved an increase in HNF4alpha loading on promoter. |
| 1493 | 17022998 | The effect was more pronounced on the rat insulin I promoter containing binding sites for both HNF4alpha and Isl1 than on the human HNF1alpha promoter lacking an Isl1 binding site. |
| 1494 | 17022998 | Moreover, Isl1 could mediate the recruitment of the cofactor CLIM2 resulting in a further transcriptional enhancement of the HNF1alpha promoter activity. |
| 1495 | 17022998 | Hepatocyte nuclear factor 4 alpha ligand binding and F domains mediate interaction and transcriptional synergy with the pancreatic islet LIM HD transcription factor Isl1. |
| 1496 | 17022998 | The orphan nuclear receptor HNF4alpha and the LIM homeodomain factor Isl1 are co-expressed in pancreatic beta-cells and are required for the differentiation and function of these endocrine cells. |
| 1497 | 17022998 | These transcriptional partners interact mainly through the HNF4alpha AF-1 module and the ligand binding domain, which contains the AF-2 module. |
| 1498 | 17022998 | Here, we showed that Isl1 could enhance the HNF4alpha-mediated activation of transcription of the HNF1alpha, PPARalpha and insulin I promoters. |
| 1499 | 17022998 | Isl1 interacted with the HNF4alpha AF-2 but also required the HNF4alpha carboxy-terminal F domain for optimal interaction and transcriptional synergy. |
| 1500 | 17022998 | More specifically, we found that naturally occurring HNF4alpha isoforms, differing only in their F domain, exhibited different abilities to interact and synergize with Isl1, extending the crucial transcriptional modulatory role of the HNF4alpha F domain. |
| 1501 | 17022998 | HNF4alpha interacted with both the homeodomain and the first LIM domain of Isl1. |
| 1502 | 17022998 | We found that the transcriptional synergy between HNF4alpha and Isl1 involved an increase in HNF4alpha loading on promoter. |
| 1503 | 17022998 | The effect was more pronounced on the rat insulin I promoter containing binding sites for both HNF4alpha and Isl1 than on the human HNF1alpha promoter lacking an Isl1 binding site. |
| 1504 | 17022998 | Moreover, Isl1 could mediate the recruitment of the cofactor CLIM2 resulting in a further transcriptional enhancement of the HNF1alpha promoter activity. |
| 1505 | 17022998 | Hepatocyte nuclear factor 4 alpha ligand binding and F domains mediate interaction and transcriptional synergy with the pancreatic islet LIM HD transcription factor Isl1. |
| 1506 | 17022998 | The orphan nuclear receptor HNF4alpha and the LIM homeodomain factor Isl1 are co-expressed in pancreatic beta-cells and are required for the differentiation and function of these endocrine cells. |
| 1507 | 17022998 | These transcriptional partners interact mainly through the HNF4alpha AF-1 module and the ligand binding domain, which contains the AF-2 module. |
| 1508 | 17022998 | Here, we showed that Isl1 could enhance the HNF4alpha-mediated activation of transcription of the HNF1alpha, PPARalpha and insulin I promoters. |
| 1509 | 17022998 | Isl1 interacted with the HNF4alpha AF-2 but also required the HNF4alpha carboxy-terminal F domain for optimal interaction and transcriptional synergy. |
| 1510 | 17022998 | More specifically, we found that naturally occurring HNF4alpha isoforms, differing only in their F domain, exhibited different abilities to interact and synergize with Isl1, extending the crucial transcriptional modulatory role of the HNF4alpha F domain. |
| 1511 | 17022998 | HNF4alpha interacted with both the homeodomain and the first LIM domain of Isl1. |
| 1512 | 17022998 | We found that the transcriptional synergy between HNF4alpha and Isl1 involved an increase in HNF4alpha loading on promoter. |
| 1513 | 17022998 | The effect was more pronounced on the rat insulin I promoter containing binding sites for both HNF4alpha and Isl1 than on the human HNF1alpha promoter lacking an Isl1 binding site. |
| 1514 | 17022998 | Moreover, Isl1 could mediate the recruitment of the cofactor CLIM2 resulting in a further transcriptional enhancement of the HNF1alpha promoter activity. |
| 1515 | 17022998 | Hepatocyte nuclear factor 4 alpha ligand binding and F domains mediate interaction and transcriptional synergy with the pancreatic islet LIM HD transcription factor Isl1. |
| 1516 | 17022998 | The orphan nuclear receptor HNF4alpha and the LIM homeodomain factor Isl1 are co-expressed in pancreatic beta-cells and are required for the differentiation and function of these endocrine cells. |
| 1517 | 17022998 | These transcriptional partners interact mainly through the HNF4alpha AF-1 module and the ligand binding domain, which contains the AF-2 module. |
| 1518 | 17022998 | Here, we showed that Isl1 could enhance the HNF4alpha-mediated activation of transcription of the HNF1alpha, PPARalpha and insulin I promoters. |
| 1519 | 17022998 | Isl1 interacted with the HNF4alpha AF-2 but also required the HNF4alpha carboxy-terminal F domain for optimal interaction and transcriptional synergy. |
| 1520 | 17022998 | More specifically, we found that naturally occurring HNF4alpha isoforms, differing only in their F domain, exhibited different abilities to interact and synergize with Isl1, extending the crucial transcriptional modulatory role of the HNF4alpha F domain. |
| 1521 | 17022998 | HNF4alpha interacted with both the homeodomain and the first LIM domain of Isl1. |
| 1522 | 17022998 | We found that the transcriptional synergy between HNF4alpha and Isl1 involved an increase in HNF4alpha loading on promoter. |
| 1523 | 17022998 | The effect was more pronounced on the rat insulin I promoter containing binding sites for both HNF4alpha and Isl1 than on the human HNF1alpha promoter lacking an Isl1 binding site. |
| 1524 | 17022998 | Moreover, Isl1 could mediate the recruitment of the cofactor CLIM2 resulting in a further transcriptional enhancement of the HNF1alpha promoter activity. |
| 1525 | 17022998 | Hepatocyte nuclear factor 4 alpha ligand binding and F domains mediate interaction and transcriptional synergy with the pancreatic islet LIM HD transcription factor Isl1. |
| 1526 | 17022998 | The orphan nuclear receptor HNF4alpha and the LIM homeodomain factor Isl1 are co-expressed in pancreatic beta-cells and are required for the differentiation and function of these endocrine cells. |
| 1527 | 17022998 | These transcriptional partners interact mainly through the HNF4alpha AF-1 module and the ligand binding domain, which contains the AF-2 module. |
| 1528 | 17022998 | Here, we showed that Isl1 could enhance the HNF4alpha-mediated activation of transcription of the HNF1alpha, PPARalpha and insulin I promoters. |
| 1529 | 17022998 | Isl1 interacted with the HNF4alpha AF-2 but also required the HNF4alpha carboxy-terminal F domain for optimal interaction and transcriptional synergy. |
| 1530 | 17022998 | More specifically, we found that naturally occurring HNF4alpha isoforms, differing only in their F domain, exhibited different abilities to interact and synergize with Isl1, extending the crucial transcriptional modulatory role of the HNF4alpha F domain. |
| 1531 | 17022998 | HNF4alpha interacted with both the homeodomain and the first LIM domain of Isl1. |
| 1532 | 17022998 | We found that the transcriptional synergy between HNF4alpha and Isl1 involved an increase in HNF4alpha loading on promoter. |
| 1533 | 17022998 | The effect was more pronounced on the rat insulin I promoter containing binding sites for both HNF4alpha and Isl1 than on the human HNF1alpha promoter lacking an Isl1 binding site. |
| 1534 | 17022998 | Moreover, Isl1 could mediate the recruitment of the cofactor CLIM2 resulting in a further transcriptional enhancement of the HNF1alpha promoter activity. |
| 1535 | 17022998 | Hepatocyte nuclear factor 4 alpha ligand binding and F domains mediate interaction and transcriptional synergy with the pancreatic islet LIM HD transcription factor Isl1. |
| 1536 | 17022998 | The orphan nuclear receptor HNF4alpha and the LIM homeodomain factor Isl1 are co-expressed in pancreatic beta-cells and are required for the differentiation and function of these endocrine cells. |
| 1537 | 17022998 | These transcriptional partners interact mainly through the HNF4alpha AF-1 module and the ligand binding domain, which contains the AF-2 module. |
| 1538 | 17022998 | Here, we showed that Isl1 could enhance the HNF4alpha-mediated activation of transcription of the HNF1alpha, PPARalpha and insulin I promoters. |
| 1539 | 17022998 | Isl1 interacted with the HNF4alpha AF-2 but also required the HNF4alpha carboxy-terminal F domain for optimal interaction and transcriptional synergy. |
| 1540 | 17022998 | More specifically, we found that naturally occurring HNF4alpha isoforms, differing only in their F domain, exhibited different abilities to interact and synergize with Isl1, extending the crucial transcriptional modulatory role of the HNF4alpha F domain. |
| 1541 | 17022998 | HNF4alpha interacted with both the homeodomain and the first LIM domain of Isl1. |
| 1542 | 17022998 | We found that the transcriptional synergy between HNF4alpha and Isl1 involved an increase in HNF4alpha loading on promoter. |
| 1543 | 17022998 | The effect was more pronounced on the rat insulin I promoter containing binding sites for both HNF4alpha and Isl1 than on the human HNF1alpha promoter lacking an Isl1 binding site. |
| 1544 | 17022998 | Moreover, Isl1 could mediate the recruitment of the cofactor CLIM2 resulting in a further transcriptional enhancement of the HNF1alpha promoter activity. |
| 1545 | 17022998 | Hepatocyte nuclear factor 4 alpha ligand binding and F domains mediate interaction and transcriptional synergy with the pancreatic islet LIM HD transcription factor Isl1. |
| 1546 | 17022998 | The orphan nuclear receptor HNF4alpha and the LIM homeodomain factor Isl1 are co-expressed in pancreatic beta-cells and are required for the differentiation and function of these endocrine cells. |
| 1547 | 17022998 | These transcriptional partners interact mainly through the HNF4alpha AF-1 module and the ligand binding domain, which contains the AF-2 module. |
| 1548 | 17022998 | Here, we showed that Isl1 could enhance the HNF4alpha-mediated activation of transcription of the HNF1alpha, PPARalpha and insulin I promoters. |
| 1549 | 17022998 | Isl1 interacted with the HNF4alpha AF-2 but also required the HNF4alpha carboxy-terminal F domain for optimal interaction and transcriptional synergy. |
| 1550 | 17022998 | More specifically, we found that naturally occurring HNF4alpha isoforms, differing only in their F domain, exhibited different abilities to interact and synergize with Isl1, extending the crucial transcriptional modulatory role of the HNF4alpha F domain. |
| 1551 | 17022998 | HNF4alpha interacted with both the homeodomain and the first LIM domain of Isl1. |
| 1552 | 17022998 | We found that the transcriptional synergy between HNF4alpha and Isl1 involved an increase in HNF4alpha loading on promoter. |
| 1553 | 17022998 | The effect was more pronounced on the rat insulin I promoter containing binding sites for both HNF4alpha and Isl1 than on the human HNF1alpha promoter lacking an Isl1 binding site. |
| 1554 | 17022998 | Moreover, Isl1 could mediate the recruitment of the cofactor CLIM2 resulting in a further transcriptional enhancement of the HNF1alpha promoter activity. |
| 1555 | 17131493 | Mutations of the MEN1 and Mody (2/3) genes were ruled out. |
| 1556 | 17204055 | Six novel mutations in the GCK gene in MODY patients. |
| 1557 | 17214554 | Mutations in the HNF4alpha gene in humans give rise to maturity-onset diabetes of the young (MODY1) characterized by defective insulin secretion by beta-cells. |
| 1558 | 17214554 | We verified the induction of selected transcripts by real-time RT-PCR, including KAI1 and AIF, both known to have apoptotic potential. |
| 1559 | 17286239 | Patients with HNF-1alpha related MODY may develop the full spectrum of diabetic complications. |
| 1560 | 17317781 | Negative regulation of c-Myc transcription by pancreas duodenum homeobox-1. |
| 1561 | 17317781 | The pancreatic and duodenal homeobox factor-1 (Pdx1) is essential for pancreatic development and insulin gene transcription, whereas c-Myc has a deleterious effect on islet function. |
| 1562 | 17317781 | However, the relationship between c-Myc and Pdx1 is poorly concerned. |
| 1563 | 17317781 | Here we demonstrated that Pdx1 could suppress c-Myc promoter activity, which relied on T cell factor (Tcf) binding elements harbored in c-Myc promoter. |
| 1564 | 17317781 | Furthermore, the transcription activity of beta-catenin/Tcf was markedly decreased on Pdx1 expression, but cotransfection of Pdx1 short hairpin RNA abrogated this effect. |
| 1565 | 17317781 | Pdx1 expression did not induce beta-catenin degradation nor did it alter their subcellular distribution. |
| 1566 | 17317781 | The mutation analysis showed that the amino acids (1-209) of Pdx1 harboring an inhibitory domain, which might lead to the reduction of beta-catenin/Tcf/p300 complex levels and attenuate their binding activity with c-Myc promoter sequences. |
| 1567 | 17317781 | Moreover, adenovirus-mediated Pdx1 interference caused cell proliferation and cytokine-induced apoptosis via the dysregulation of c-Myc transcription. |
| 1568 | 17317781 | These results indicated that the Pdx1 functioned as a key regulator for maintenance of beta-cell function, at least in part, through controlling c-Myc expression and the loss of its regulatory function may be an alternative mechanism for beta-cell neogenesis and apoptosis found in diabetes. |
| 1569 | 17327436 | Specifically, we determined patterns of common sequence variation in the genes encoding Gck, Ipf1, Tcf2, and NeuroD1 (MODY2 and MODY4-MODY6, respectively), selected a comprehensive set of 107 tag single nucleotide polymorphisms (SNPs) that captured common variation, and genotyped each in 4,206 patients and control subjects from Sweden, Finland, and Canada (including family-based studies and unrelated case-control subjects). |
| 1570 | 17327436 | We combined these results with our previous studies on HNF4alpha and TCF1 and explicitly tested for gene-gene interactions among these variants and with several known type 2 diabetes susceptibility loci, and we found no genetic interactions between these six genes. |
| 1571 | 17343826 | The human intestinal fatty acid binding protein (hFABP2) gene is regulated by HNF-4alpha. |
| 1572 | 17343826 | The aim of this study was to investigate the regulation of hFABP2 by the endodermal hepatocyte nuclear factor 4alpha (HNF-4alpha), involved in regulation of genes of fatty acid metabolism and differentiation. |
| 1573 | 17343826 | Electromobility shift assays demonstrated that HNF-4alpha binds at position -324 to -336 within the hFABP2 promoter. |
| 1574 | 17343826 | Mutation of this HNF-4 binding site abolished the luciferase reporter activity of hFABP2 in postconfluent Caco-2 cells. |
| 1575 | 17343826 | In HeLa cells, this mutation reduced the activation of the hFABP2 promoter by HNF-4alpha by about 50%. |
| 1576 | 17343826 | Studying genotype interactions of hFABP2 and HNF-4alpha, that are both candidate genes for diabetes type 2, may be a powerful approach. |
| 1577 | 17343826 | The human intestinal fatty acid binding protein (hFABP2) gene is regulated by HNF-4alpha. |
| 1578 | 17343826 | The aim of this study was to investigate the regulation of hFABP2 by the endodermal hepatocyte nuclear factor 4alpha (HNF-4alpha), involved in regulation of genes of fatty acid metabolism and differentiation. |
| 1579 | 17343826 | Electromobility shift assays demonstrated that HNF-4alpha binds at position -324 to -336 within the hFABP2 promoter. |
| 1580 | 17343826 | Mutation of this HNF-4 binding site abolished the luciferase reporter activity of hFABP2 in postconfluent Caco-2 cells. |
| 1581 | 17343826 | In HeLa cells, this mutation reduced the activation of the hFABP2 promoter by HNF-4alpha by about 50%. |
| 1582 | 17343826 | Studying genotype interactions of hFABP2 and HNF-4alpha, that are both candidate genes for diabetes type 2, may be a powerful approach. |
| 1583 | 17343826 | The human intestinal fatty acid binding protein (hFABP2) gene is regulated by HNF-4alpha. |
| 1584 | 17343826 | The aim of this study was to investigate the regulation of hFABP2 by the endodermal hepatocyte nuclear factor 4alpha (HNF-4alpha), involved in regulation of genes of fatty acid metabolism and differentiation. |
| 1585 | 17343826 | Electromobility shift assays demonstrated that HNF-4alpha binds at position -324 to -336 within the hFABP2 promoter. |
| 1586 | 17343826 | Mutation of this HNF-4 binding site abolished the luciferase reporter activity of hFABP2 in postconfluent Caco-2 cells. |
| 1587 | 17343826 | In HeLa cells, this mutation reduced the activation of the hFABP2 promoter by HNF-4alpha by about 50%. |
| 1588 | 17343826 | Studying genotype interactions of hFABP2 and HNF-4alpha, that are both candidate genes for diabetes type 2, may be a powerful approach. |
| 1589 | 17343826 | The human intestinal fatty acid binding protein (hFABP2) gene is regulated by HNF-4alpha. |
| 1590 | 17343826 | The aim of this study was to investigate the regulation of hFABP2 by the endodermal hepatocyte nuclear factor 4alpha (HNF-4alpha), involved in regulation of genes of fatty acid metabolism and differentiation. |
| 1591 | 17343826 | Electromobility shift assays demonstrated that HNF-4alpha binds at position -324 to -336 within the hFABP2 promoter. |
| 1592 | 17343826 | Mutation of this HNF-4 binding site abolished the luciferase reporter activity of hFABP2 in postconfluent Caco-2 cells. |
| 1593 | 17343826 | In HeLa cells, this mutation reduced the activation of the hFABP2 promoter by HNF-4alpha by about 50%. |
| 1594 | 17343826 | Studying genotype interactions of hFABP2 and HNF-4alpha, that are both candidate genes for diabetes type 2, may be a powerful approach. |
| 1595 | 17343826 | The human intestinal fatty acid binding protein (hFABP2) gene is regulated by HNF-4alpha. |
| 1596 | 17343826 | The aim of this study was to investigate the regulation of hFABP2 by the endodermal hepatocyte nuclear factor 4alpha (HNF-4alpha), involved in regulation of genes of fatty acid metabolism and differentiation. |
| 1597 | 17343826 | Electromobility shift assays demonstrated that HNF-4alpha binds at position -324 to -336 within the hFABP2 promoter. |
| 1598 | 17343826 | Mutation of this HNF-4 binding site abolished the luciferase reporter activity of hFABP2 in postconfluent Caco-2 cells. |
| 1599 | 17343826 | In HeLa cells, this mutation reduced the activation of the hFABP2 promoter by HNF-4alpha by about 50%. |
| 1600 | 17343826 | Studying genotype interactions of hFABP2 and HNF-4alpha, that are both candidate genes for diabetes type 2, may be a powerful approach. |
| 1601 | 17343826 | The human intestinal fatty acid binding protein (hFABP2) gene is regulated by HNF-4alpha. |
| 1602 | 17343826 | The aim of this study was to investigate the regulation of hFABP2 by the endodermal hepatocyte nuclear factor 4alpha (HNF-4alpha), involved in regulation of genes of fatty acid metabolism and differentiation. |
| 1603 | 17343826 | Electromobility shift assays demonstrated that HNF-4alpha binds at position -324 to -336 within the hFABP2 promoter. |
| 1604 | 17343826 | Mutation of this HNF-4 binding site abolished the luciferase reporter activity of hFABP2 in postconfluent Caco-2 cells. |
| 1605 | 17343826 | In HeLa cells, this mutation reduced the activation of the hFABP2 promoter by HNF-4alpha by about 50%. |
| 1606 | 17343826 | Studying genotype interactions of hFABP2 and HNF-4alpha, that are both candidate genes for diabetes type 2, may be a powerful approach. |
| 1607 | 17403778 | Here we demonstrate that the proliferative response of beta-cells is dependent on the orphan nuclear receptor hepatocyte nuclear factor-4alpha (HNF-4alpha), the gene that is mutated in Maturity-Onset Diabetes of the Young 1 (MODY1). |
| 1608 | 17403778 | This phenotype correlates with the down-regulation of suppression of tumorigenicity 5 (ST5) in HNF-4alpha mutants, which we identify as a novel regulator of ERK phosphorylation in beta-cells and a direct transcriptional target of HNF-4alpha in vivo. |
| 1609 | 17403778 | Here we demonstrate that the proliferative response of beta-cells is dependent on the orphan nuclear receptor hepatocyte nuclear factor-4alpha (HNF-4alpha), the gene that is mutated in Maturity-Onset Diabetes of the Young 1 (MODY1). |
| 1610 | 17403778 | This phenotype correlates with the down-regulation of suppression of tumorigenicity 5 (ST5) in HNF-4alpha mutants, which we identify as a novel regulator of ERK phosphorylation in beta-cells and a direct transcriptional target of HNF-4alpha in vivo. |
| 1611 | 17425917 | Maturity-onset diabetes of the young (MODY) is a type of non-insulin-dependent diabetes mellitus caused by rare autosomal-dominant mutations. |
| 1612 | 17466274 | The marker screening enabled us to identify significant disease association in the lipopolysaccharide binding protein (LBP) but not in the HNF4A locus. |
| 1613 | 17551475 | These include the enzyme glucokinase, which causes MODY2, and the transcription factors HNF- 4 alpha, TCF1, I PF-1, TCF2, and NeuroD1, which cause MODY1, 3, 4, 5, and 6, respectively. |
| 1614 | 17805472 | This study was aimed to assess the association of the two single nucleotide polymorphisms (SNPs) near P2 promoter (rs1884614 and rs2144908) of hepatocyte nuclear factor-4alpha (HNF4A) with insulin secretion index and type 2 diabetes in Thais. |
| 1615 | 17882463 | Recent advances provide insights into how poorly water-soluble lipid nutrients [LCFA; retinoic acid (RA)] and their metabolites (long chain fatty acyl Coenzyme A, LCFA-CoA) reach nuclei, bind their cognate ligand-activated receptors, and regulate transcription for signaling lipid and glucose catabolism or storage: (i) while serum and cytoplasmic LCFA levels are in the 200 mircroM-mM range, real-time imaging recently revealed that LCFA and LCFA-CoA are also located within nuclei (nM range); (ii) sensitive fluorescence binding assays show that LCFA-activated nuclear receptors [peroxisome proliferator-activated receptor-alpha (PPARalpha) and hepatocyte nuclear factor 4alpha (HNF4alpha)] exhibit high affinity (low nM KdS) for LCFA (PPARalpha) and/or LCFA-CoA (PPARalpha, HNF4alpha)-in the same range as nuclear levels of these ligands; (iii) live and fixed cell immunolabeling and imaging revealed that some cytoplasmic lipid binding proteins [liver fatty acid binding protein (L-FABP), acyl CoA binding protein (ACBP), cellular retinoic acid binding protein-2 (CRABP-2)] enter nuclei, bind nuclear receptors (PPARalpha, HNF4alpha, CRABP-2), and activate transcription of genes in fatty acid and glucose metabolism; and (iv) studies with gene ablated mice provided physiological relevance of LCFA and LCFA-CoA binding proteins in nuclear signaling. |
| 1616 | 17919177 | Maturity-onset diabetes of the young (MODY) is a monogenic form of type 2 diabetes mellitus that is characterized by impairment of glucose-stimulated insulin secretion from pancreatic beta-cells. |
| 1617 | 17919177 | We previously reported that heterozygous mutations of the hepatocyte nuclear factor (HNF)-1alpha gene cause a form of MODY (MODY3). |
| 1618 | 17919177 | In addition, we have demonstrated that collectrin forms a complex with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex by direct interaction with snapin, a protein that is thought to be involved in neurotransmission by binding to synaptosomal-associated protein, 25 KD (SNAP25). |
| 1619 | 17919177 | Collectrin favours the formation of SNARE complexes and controls insulin exocytosis. |
| 1620 | 17919177 | Maturity-onset diabetes of the young (MODY) is a monogenic form of type 2 diabetes mellitus that is characterized by impairment of glucose-stimulated insulin secretion from pancreatic beta-cells. |
| 1621 | 17919177 | We previously reported that heterozygous mutations of the hepatocyte nuclear factor (HNF)-1alpha gene cause a form of MODY (MODY3). |
| 1622 | 17919177 | In addition, we have demonstrated that collectrin forms a complex with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex by direct interaction with snapin, a protein that is thought to be involved in neurotransmission by binding to synaptosomal-associated protein, 25 KD (SNAP25). |
| 1623 | 17919177 | Collectrin favours the formation of SNARE complexes and controls insulin exocytosis. |
| 1624 | 17923767 | Distinct roles of HNF1beta, HNF1alpha, and HNF4alpha in regulating pancreas development, beta-cell function and growth. |
| 1625 | 17923767 | Mutations in the genes encoding transcriptional regulators HNF1beta (TCF2), HNF1alpha (TCF1), and HNF4alpha cause autosomal dominant diabetes (also known as maturity-onset diabetes of the young). |
| 1626 | 17923767 | By contrast, HNF1alpha and HNF4alpha have been shown to regulate the function of differentiated beta-cells. |
| 1627 | 17923767 | HNF1alpha and HNF4alpha mutations in patients thus cause decreased glucose-induced insulin secretion that leads to a progressive form of diabetes. |
| 1628 | 17923767 | Collectively, these findings implicate HNF1beta as a regulator of pancreas organogenesis and differentiation, whereas HNF1alpha and HNF4alpha primarily regulate both growth and function of islet beta-cells. |
| 1629 | 17923767 | Distinct roles of HNF1beta, HNF1alpha, and HNF4alpha in regulating pancreas development, beta-cell function and growth. |
| 1630 | 17923767 | Mutations in the genes encoding transcriptional regulators HNF1beta (TCF2), HNF1alpha (TCF1), and HNF4alpha cause autosomal dominant diabetes (also known as maturity-onset diabetes of the young). |
| 1631 | 17923767 | By contrast, HNF1alpha and HNF4alpha have been shown to regulate the function of differentiated beta-cells. |
| 1632 | 17923767 | HNF1alpha and HNF4alpha mutations in patients thus cause decreased glucose-induced insulin secretion that leads to a progressive form of diabetes. |
| 1633 | 17923767 | Collectively, these findings implicate HNF1beta as a regulator of pancreas organogenesis and differentiation, whereas HNF1alpha and HNF4alpha primarily regulate both growth and function of islet beta-cells. |
| 1634 | 17923767 | Distinct roles of HNF1beta, HNF1alpha, and HNF4alpha in regulating pancreas development, beta-cell function and growth. |
| 1635 | 17923767 | Mutations in the genes encoding transcriptional regulators HNF1beta (TCF2), HNF1alpha (TCF1), and HNF4alpha cause autosomal dominant diabetes (also known as maturity-onset diabetes of the young). |
| 1636 | 17923767 | By contrast, HNF1alpha and HNF4alpha have been shown to regulate the function of differentiated beta-cells. |
| 1637 | 17923767 | HNF1alpha and HNF4alpha mutations in patients thus cause decreased glucose-induced insulin secretion that leads to a progressive form of diabetes. |
| 1638 | 17923767 | Collectively, these findings implicate HNF1beta as a regulator of pancreas organogenesis and differentiation, whereas HNF1alpha and HNF4alpha primarily regulate both growth and function of islet beta-cells. |
| 1639 | 17923767 | Distinct roles of HNF1beta, HNF1alpha, and HNF4alpha in regulating pancreas development, beta-cell function and growth. |
| 1640 | 17923767 | Mutations in the genes encoding transcriptional regulators HNF1beta (TCF2), HNF1alpha (TCF1), and HNF4alpha cause autosomal dominant diabetes (also known as maturity-onset diabetes of the young). |
| 1641 | 17923767 | By contrast, HNF1alpha and HNF4alpha have been shown to regulate the function of differentiated beta-cells. |
| 1642 | 17923767 | HNF1alpha and HNF4alpha mutations in patients thus cause decreased glucose-induced insulin secretion that leads to a progressive form of diabetes. |
| 1643 | 17923767 | Collectively, these findings implicate HNF1beta as a regulator of pancreas organogenesis and differentiation, whereas HNF1alpha and HNF4alpha primarily regulate both growth and function of islet beta-cells. |
| 1644 | 17923767 | Distinct roles of HNF1beta, HNF1alpha, and HNF4alpha in regulating pancreas development, beta-cell function and growth. |
| 1645 | 17923767 | Mutations in the genes encoding transcriptional regulators HNF1beta (TCF2), HNF1alpha (TCF1), and HNF4alpha cause autosomal dominant diabetes (also known as maturity-onset diabetes of the young). |
| 1646 | 17923767 | By contrast, HNF1alpha and HNF4alpha have been shown to regulate the function of differentiated beta-cells. |
| 1647 | 17923767 | HNF1alpha and HNF4alpha mutations in patients thus cause decreased glucose-induced insulin secretion that leads to a progressive form of diabetes. |
| 1648 | 17923767 | Collectively, these findings implicate HNF1beta as a regulator of pancreas organogenesis and differentiation, whereas HNF1alpha and HNF4alpha primarily regulate both growth and function of islet beta-cells. |
| 1649 | 17937063 | Four novel mutations, including the first gross deletion in TCF1, identified in HNF-4alpha, GCK and TCF1 in patients with MODY in Israel. |
| 1650 | 17937063 | Fifty-nine unrelated Israeli patients with MODY were assessed for mutations in the three common MODY genes: hepatocyte nuclear factor (HNF)-4alpha, glucokinase (GCK), and transcription factor 1 (TCF1). |
| 1651 | 17937063 | Four mutations were novel, including the first gross deletion ever described in the TCF1 gene. |
| 1652 | 17993259 | We show here that insulin stimulates cell proliferation and c-Myc expression in colon cancer cell lines HT29 and Caco-2, intestinal non-cancer cell line IEC-6, and primary fetal rat intestinal cell (FRIC) cultures. |
| 1653 | 17993259 | The effect of insulin was blocked by phosphoinositide-3 Kinase (PI3K) inhibition, but only partially attenuated by inhibition of Protein kinase B (PKB), indicating the existence of both PKB-dependent and -independent mechanisms. |
| 1654 | 17993259 | The PKB-dependent mechanism of insulin-stimulated c-Myc expression in HT29 cells was shown to involve the activation of mTOR in c-Myc translation. |
| 1655 | 17993259 | In the investigation of the PKB-independent mechanism, we found that insulin-induced nuclear translocation of beta-catenin (beta-cat), an effector of Wnt signaling. |
| 1656 | 17993259 | Finally, chromatin immunoprecipitation (ChIP) detected significant increases in the binding of beta-cat to two TCF binding sites of the human c-Myc promoter following insulin treatment. |
| 1657 | 17993259 | Our observations support the existence of crosstalk between insulin and Wnt signaling pathways, and suggest that the crosstalk involves a PKB-independent mechanism. |
| 1658 | 17996499 | Expression of HNF-4alpha (MODY1), HNF-1beta (MODY5), and HNF-1alpha (MODY3) proteins in the developing mouse pancreas. |
| 1659 | 17996499 | The type 1, 3, and 5 forms of maturity-onset diabetes of the young (MODY) are caused by mutations of the genes encoding hepatocyte nuclear factor (HNF)-4alpha, HNF-1alpha, and HNF-1beta, respectively [Yamagata, K., Oda, N., Kaisaki, P.J., Menzel, S., Furuta, H., Vaxillaire, M., et al., 1996a. |
| 1660 | 17996499 | Mutation in hepatocyte nuclear factor-1beta gene (TCF2) associated with MODY. |
| 1661 | 17996499 | We performed an immunohistochemical study to investigate its expression in comparison with the expression of HNF-1alpha and HNF-1beta. |
| 1662 | 17996499 | HNF-4alpha and HNF-1beta were initially expressed by Pdx1(+) common progenitor cells and neurogenin3(+) (Ngn3(+)) endocrine precursor cells during the first transition, but expression of HNF-1beta and either HNF-4alpha or HNF-1alpha became complementary around the end of the second transition (E15.5). |
| 1663 | 17996499 | In the mature pancreas, HNF-4alpha was expressed by glucagon-positive alpha-cells, insulin-positive beta-cells, somatostatin-positive delta-cells, and pancreatic polypeptide-positive PP-cells, as well as by pancreatic exocrine cells and ductal cells. |
| 1664 | 17996499 | Most of the HNF-4alpha(+) cells were also positive for HNF-1alpha, but HNF-4alpha expression in some non-beta-cells was remarkably high, and this was not paralleled by high HNF-1alpha expression. |
| 1665 | 17996499 | Expression of HNF-4alpha (MODY1), HNF-1beta (MODY5), and HNF-1alpha (MODY3) proteins in the developing mouse pancreas. |
| 1666 | 17996499 | The type 1, 3, and 5 forms of maturity-onset diabetes of the young (MODY) are caused by mutations of the genes encoding hepatocyte nuclear factor (HNF)-4alpha, HNF-1alpha, and HNF-1beta, respectively [Yamagata, K., Oda, N., Kaisaki, P.J., Menzel, S., Furuta, H., Vaxillaire, M., et al., 1996a. |
| 1667 | 17996499 | Mutation in hepatocyte nuclear factor-1beta gene (TCF2) associated with MODY. |
| 1668 | 17996499 | We performed an immunohistochemical study to investigate its expression in comparison with the expression of HNF-1alpha and HNF-1beta. |
| 1669 | 17996499 | HNF-4alpha and HNF-1beta were initially expressed by Pdx1(+) common progenitor cells and neurogenin3(+) (Ngn3(+)) endocrine precursor cells during the first transition, but expression of HNF-1beta and either HNF-4alpha or HNF-1alpha became complementary around the end of the second transition (E15.5). |
| 1670 | 17996499 | In the mature pancreas, HNF-4alpha was expressed by glucagon-positive alpha-cells, insulin-positive beta-cells, somatostatin-positive delta-cells, and pancreatic polypeptide-positive PP-cells, as well as by pancreatic exocrine cells and ductal cells. |
| 1671 | 17996499 | Most of the HNF-4alpha(+) cells were also positive for HNF-1alpha, but HNF-4alpha expression in some non-beta-cells was remarkably high, and this was not paralleled by high HNF-1alpha expression. |
| 1672 | 17996499 | Expression of HNF-4alpha (MODY1), HNF-1beta (MODY5), and HNF-1alpha (MODY3) proteins in the developing mouse pancreas. |
| 1673 | 17996499 | The type 1, 3, and 5 forms of maturity-onset diabetes of the young (MODY) are caused by mutations of the genes encoding hepatocyte nuclear factor (HNF)-4alpha, HNF-1alpha, and HNF-1beta, respectively [Yamagata, K., Oda, N., Kaisaki, P.J., Menzel, S., Furuta, H., Vaxillaire, M., et al., 1996a. |
| 1674 | 17996499 | Mutation in hepatocyte nuclear factor-1beta gene (TCF2) associated with MODY. |
| 1675 | 17996499 | We performed an immunohistochemical study to investigate its expression in comparison with the expression of HNF-1alpha and HNF-1beta. |
| 1676 | 17996499 | HNF-4alpha and HNF-1beta were initially expressed by Pdx1(+) common progenitor cells and neurogenin3(+) (Ngn3(+)) endocrine precursor cells during the first transition, but expression of HNF-1beta and either HNF-4alpha or HNF-1alpha became complementary around the end of the second transition (E15.5). |
| 1677 | 17996499 | In the mature pancreas, HNF-4alpha was expressed by glucagon-positive alpha-cells, insulin-positive beta-cells, somatostatin-positive delta-cells, and pancreatic polypeptide-positive PP-cells, as well as by pancreatic exocrine cells and ductal cells. |
| 1678 | 17996499 | Most of the HNF-4alpha(+) cells were also positive for HNF-1alpha, but HNF-4alpha expression in some non-beta-cells was remarkably high, and this was not paralleled by high HNF-1alpha expression. |
| 1679 | 17996499 | Expression of HNF-4alpha (MODY1), HNF-1beta (MODY5), and HNF-1alpha (MODY3) proteins in the developing mouse pancreas. |
| 1680 | 17996499 | The type 1, 3, and 5 forms of maturity-onset diabetes of the young (MODY) are caused by mutations of the genes encoding hepatocyte nuclear factor (HNF)-4alpha, HNF-1alpha, and HNF-1beta, respectively [Yamagata, K., Oda, N., Kaisaki, P.J., Menzel, S., Furuta, H., Vaxillaire, M., et al., 1996a. |
| 1681 | 17996499 | Mutation in hepatocyte nuclear factor-1beta gene (TCF2) associated with MODY. |
| 1682 | 17996499 | We performed an immunohistochemical study to investigate its expression in comparison with the expression of HNF-1alpha and HNF-1beta. |
| 1683 | 17996499 | HNF-4alpha and HNF-1beta were initially expressed by Pdx1(+) common progenitor cells and neurogenin3(+) (Ngn3(+)) endocrine precursor cells during the first transition, but expression of HNF-1beta and either HNF-4alpha or HNF-1alpha became complementary around the end of the second transition (E15.5). |
| 1684 | 17996499 | In the mature pancreas, HNF-4alpha was expressed by glucagon-positive alpha-cells, insulin-positive beta-cells, somatostatin-positive delta-cells, and pancreatic polypeptide-positive PP-cells, as well as by pancreatic exocrine cells and ductal cells. |
| 1685 | 17996499 | Most of the HNF-4alpha(+) cells were also positive for HNF-1alpha, but HNF-4alpha expression in some non-beta-cells was remarkably high, and this was not paralleled by high HNF-1alpha expression. |
| 1686 | 17996499 | Expression of HNF-4alpha (MODY1), HNF-1beta (MODY5), and HNF-1alpha (MODY3) proteins in the developing mouse pancreas. |
| 1687 | 17996499 | The type 1, 3, and 5 forms of maturity-onset diabetes of the young (MODY) are caused by mutations of the genes encoding hepatocyte nuclear factor (HNF)-4alpha, HNF-1alpha, and HNF-1beta, respectively [Yamagata, K., Oda, N., Kaisaki, P.J., Menzel, S., Furuta, H., Vaxillaire, M., et al., 1996a. |
| 1688 | 17996499 | Mutation in hepatocyte nuclear factor-1beta gene (TCF2) associated with MODY. |
| 1689 | 17996499 | We performed an immunohistochemical study to investigate its expression in comparison with the expression of HNF-1alpha and HNF-1beta. |
| 1690 | 17996499 | HNF-4alpha and HNF-1beta were initially expressed by Pdx1(+) common progenitor cells and neurogenin3(+) (Ngn3(+)) endocrine precursor cells during the first transition, but expression of HNF-1beta and either HNF-4alpha or HNF-1alpha became complementary around the end of the second transition (E15.5). |
| 1691 | 17996499 | In the mature pancreas, HNF-4alpha was expressed by glucagon-positive alpha-cells, insulin-positive beta-cells, somatostatin-positive delta-cells, and pancreatic polypeptide-positive PP-cells, as well as by pancreatic exocrine cells and ductal cells. |
| 1692 | 17996499 | Most of the HNF-4alpha(+) cells were also positive for HNF-1alpha, but HNF-4alpha expression in some non-beta-cells was remarkably high, and this was not paralleled by high HNF-1alpha expression. |
| 1693 | 17996499 | Expression of HNF-4alpha (MODY1), HNF-1beta (MODY5), and HNF-1alpha (MODY3) proteins in the developing mouse pancreas. |
| 1694 | 17996499 | The type 1, 3, and 5 forms of maturity-onset diabetes of the young (MODY) are caused by mutations of the genes encoding hepatocyte nuclear factor (HNF)-4alpha, HNF-1alpha, and HNF-1beta, respectively [Yamagata, K., Oda, N., Kaisaki, P.J., Menzel, S., Furuta, H., Vaxillaire, M., et al., 1996a. |
| 1695 | 17996499 | Mutation in hepatocyte nuclear factor-1beta gene (TCF2) associated with MODY. |
| 1696 | 17996499 | We performed an immunohistochemical study to investigate its expression in comparison with the expression of HNF-1alpha and HNF-1beta. |
| 1697 | 17996499 | HNF-4alpha and HNF-1beta were initially expressed by Pdx1(+) common progenitor cells and neurogenin3(+) (Ngn3(+)) endocrine precursor cells during the first transition, but expression of HNF-1beta and either HNF-4alpha or HNF-1alpha became complementary around the end of the second transition (E15.5). |
| 1698 | 17996499 | In the mature pancreas, HNF-4alpha was expressed by glucagon-positive alpha-cells, insulin-positive beta-cells, somatostatin-positive delta-cells, and pancreatic polypeptide-positive PP-cells, as well as by pancreatic exocrine cells and ductal cells. |
| 1699 | 17996499 | Most of the HNF-4alpha(+) cells were also positive for HNF-1alpha, but HNF-4alpha expression in some non-beta-cells was remarkably high, and this was not paralleled by high HNF-1alpha expression. |
| 1700 | 18058600 | Since duct cells are thought to be precursors of endocrine cells and HNF-6 is involved in the regulation of the expression of HNF-4alpha and -1beta, genes that cause maturity onset diabetes of the young (MODY), we hypothesized that the sustained expression of HNF-6 would affect beta-cell function. |
| 1701 | 18058600 | We generated transgenic mice over-expressing human HNF-6 using the mouse insulin I promoter (MIP). |
| 1702 | 18162503 | Evidence of interaction between PPARG2 and HNF4A contributing to variation in insulin sensitivity in Mexican Americans. |
| 1703 | 18192540 | Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes. |
| 1704 | 18221440 | We report an interesting and unique case of an overweight adolescent with a novel mutation of the maturity-onset diabetes of the young (MODY)3 gene [hepatocyte nuclear factor-1 alpha (HNF-1alpha)] and positive islet cell autoantibodies. |
| 1705 | 18221440 | Initial hemoglobin A1c was 11.9%, with fasting glucose of 234 mg/dL and fasting insulin 10.7 microU/mL. |
| 1706 | 18391435 | Crystallization of hepatocyte nuclear factor 4 alpha (HNF4 alpha) in complex with the HNF1 alpha promoter element. |
| 1707 | 18391435 | In order to understand the molecular mechanism of promoter recognition and the molecular basis of disease-causing mutations, the recombinant HNF4alpha DNA-binding domain was prepared and used in a study of its binding properties and in crystallization with a 21-mer DNA fragment that contains the promoter element of another MODY gene, HNF1alpha. |
| 1708 | 18391435 | Crystallization of hepatocyte nuclear factor 4 alpha (HNF4 alpha) in complex with the HNF1 alpha promoter element. |
| 1709 | 18391435 | In order to understand the molecular mechanism of promoter recognition and the molecular basis of disease-causing mutations, the recombinant HNF4alpha DNA-binding domain was prepared and used in a study of its binding properties and in crystallization with a 21-mer DNA fragment that contains the promoter element of another MODY gene, HNF1alpha. |
| 1710 | 18436708 | Most valuable breakthroughs in the genetics of type 2 diabetes for the past two decades have arisen from candidate gene studies and familial linkage analysis of maturity-onset diabetes of the young (MODY), an autosomal dominant form of diabetes typically occurring before 25 years of age caused by primary insulin secretion defects. |
| 1711 | 18436708 | MODY can result from mutations in at least six different genes encoding the glucose sensor enzyme glucokinase and transcription factors that participate in a regulatory network essential for adult beta-cell function. |
| 1712 | 18436708 | Most valuable breakthroughs in the genetics of type 2 diabetes for the past two decades have arisen from candidate gene studies and familial linkage analysis of maturity-onset diabetes of the young (MODY), an autosomal dominant form of diabetes typically occurring before 25 years of age caused by primary insulin secretion defects. |
| 1713 | 18436708 | MODY can result from mutations in at least six different genes encoding the glucose sensor enzyme glucokinase and transcription factors that participate in a regulatory network essential for adult beta-cell function. |
| 1714 | 18474611 | The MODY1 gene for hepatocyte nuclear factor 4alpha and a feedback loop control COUP-TFII expression in pancreatic beta cells. |
| 1715 | 18474611 | Knockout mice with the heterozygous deletion of the gene for chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) or the complete disruption of the gene for hepatocyte nuclear factor 4alpha (HNF4alpha) in pancreatic beta cells have similar insulin secretion defects, leading us to hypothesize that there is transcriptional cross talk between these two nuclear receptors. |
| 1716 | 18474611 | Here, we demonstrate specific HNF4alpha activation of a reporter plasmid containing the COUP-TFII gene promoter region in transfected pancreatic beta cells. |
| 1717 | 18474611 | The stable association of the endogenous HNF4alpha with a region of the COUP-TFII gene promoter that contains a direct repeat 1 (DR-1) binding site was revealed by chromatin immunoprecipitation. |
| 1718 | 18474611 | Mutation experiments showed that this DR-1 site is essential for HNF4alpha transactivation of COUP-TFII. |
| 1719 | 18474611 | The dominant negative suppression of HNF4alpha function decreased endogenous COUP-TFII expression, and the specific inactivation of COUP-TFII by small interfering RNA caused HNF4alpha mRNA levels in 832/13 INS-1 cells to decrease. |
| 1720 | 18474611 | This positive regulation of HNF4alpha by COUP-TFII was confirmed by the adenovirus-mediated overexpression of human COUP-TFII (hCOUP-TFII), which increased HNF4alpha mRNA levels in 832/13 INS-1 cells and in mouse pancreatic islets. |
| 1721 | 18474611 | Finally, hCOUP-TFII overexpression showed that there is direct COUP-TFII autorepression, as COUP-TFII occupies the proximal DR-1 binding site of its own gene in vivo. |
| 1722 | 18474611 | Therefore, COUP-TFII may contribute to the control of insulin secretion through the complex HNF4alpha/maturity-onset diabetes of the young 1 (MODY1) transcription factor network operating in beta cells. |
| 1723 | 18474611 | The MODY1 gene for hepatocyte nuclear factor 4alpha and a feedback loop control COUP-TFII expression in pancreatic beta cells. |
| 1724 | 18474611 | Knockout mice with the heterozygous deletion of the gene for chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) or the complete disruption of the gene for hepatocyte nuclear factor 4alpha (HNF4alpha) in pancreatic beta cells have similar insulin secretion defects, leading us to hypothesize that there is transcriptional cross talk between these two nuclear receptors. |
| 1725 | 18474611 | Here, we demonstrate specific HNF4alpha activation of a reporter plasmid containing the COUP-TFII gene promoter region in transfected pancreatic beta cells. |
| 1726 | 18474611 | The stable association of the endogenous HNF4alpha with a region of the COUP-TFII gene promoter that contains a direct repeat 1 (DR-1) binding site was revealed by chromatin immunoprecipitation. |
| 1727 | 18474611 | Mutation experiments showed that this DR-1 site is essential for HNF4alpha transactivation of COUP-TFII. |
| 1728 | 18474611 | The dominant negative suppression of HNF4alpha function decreased endogenous COUP-TFII expression, and the specific inactivation of COUP-TFII by small interfering RNA caused HNF4alpha mRNA levels in 832/13 INS-1 cells to decrease. |
| 1729 | 18474611 | This positive regulation of HNF4alpha by COUP-TFII was confirmed by the adenovirus-mediated overexpression of human COUP-TFII (hCOUP-TFII), which increased HNF4alpha mRNA levels in 832/13 INS-1 cells and in mouse pancreatic islets. |
| 1730 | 18474611 | Finally, hCOUP-TFII overexpression showed that there is direct COUP-TFII autorepression, as COUP-TFII occupies the proximal DR-1 binding site of its own gene in vivo. |
| 1731 | 18474611 | Therefore, COUP-TFII may contribute to the control of insulin secretion through the complex HNF4alpha/maturity-onset diabetes of the young 1 (MODY1) transcription factor network operating in beta cells. |
| 1732 | 18474611 | The MODY1 gene for hepatocyte nuclear factor 4alpha and a feedback loop control COUP-TFII expression in pancreatic beta cells. |
| 1733 | 18474611 | Knockout mice with the heterozygous deletion of the gene for chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) or the complete disruption of the gene for hepatocyte nuclear factor 4alpha (HNF4alpha) in pancreatic beta cells have similar insulin secretion defects, leading us to hypothesize that there is transcriptional cross talk between these two nuclear receptors. |
| 1734 | 18474611 | Here, we demonstrate specific HNF4alpha activation of a reporter plasmid containing the COUP-TFII gene promoter region in transfected pancreatic beta cells. |
| 1735 | 18474611 | The stable association of the endogenous HNF4alpha with a region of the COUP-TFII gene promoter that contains a direct repeat 1 (DR-1) binding site was revealed by chromatin immunoprecipitation. |
| 1736 | 18474611 | Mutation experiments showed that this DR-1 site is essential for HNF4alpha transactivation of COUP-TFII. |
| 1737 | 18474611 | The dominant negative suppression of HNF4alpha function decreased endogenous COUP-TFII expression, and the specific inactivation of COUP-TFII by small interfering RNA caused HNF4alpha mRNA levels in 832/13 INS-1 cells to decrease. |
| 1738 | 18474611 | This positive regulation of HNF4alpha by COUP-TFII was confirmed by the adenovirus-mediated overexpression of human COUP-TFII (hCOUP-TFII), which increased HNF4alpha mRNA levels in 832/13 INS-1 cells and in mouse pancreatic islets. |
| 1739 | 18474611 | Finally, hCOUP-TFII overexpression showed that there is direct COUP-TFII autorepression, as COUP-TFII occupies the proximal DR-1 binding site of its own gene in vivo. |
| 1740 | 18474611 | Therefore, COUP-TFII may contribute to the control of insulin secretion through the complex HNF4alpha/maturity-onset diabetes of the young 1 (MODY1) transcription factor network operating in beta cells. |
| 1741 | 18474611 | The MODY1 gene for hepatocyte nuclear factor 4alpha and a feedback loop control COUP-TFII expression in pancreatic beta cells. |
| 1742 | 18474611 | Knockout mice with the heterozygous deletion of the gene for chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) or the complete disruption of the gene for hepatocyte nuclear factor 4alpha (HNF4alpha) in pancreatic beta cells have similar insulin secretion defects, leading us to hypothesize that there is transcriptional cross talk between these two nuclear receptors. |
| 1743 | 18474611 | Here, we demonstrate specific HNF4alpha activation of a reporter plasmid containing the COUP-TFII gene promoter region in transfected pancreatic beta cells. |
| 1744 | 18474611 | The stable association of the endogenous HNF4alpha with a region of the COUP-TFII gene promoter that contains a direct repeat 1 (DR-1) binding site was revealed by chromatin immunoprecipitation. |
| 1745 | 18474611 | Mutation experiments showed that this DR-1 site is essential for HNF4alpha transactivation of COUP-TFII. |
| 1746 | 18474611 | The dominant negative suppression of HNF4alpha function decreased endogenous COUP-TFII expression, and the specific inactivation of COUP-TFII by small interfering RNA caused HNF4alpha mRNA levels in 832/13 INS-1 cells to decrease. |
| 1747 | 18474611 | This positive regulation of HNF4alpha by COUP-TFII was confirmed by the adenovirus-mediated overexpression of human COUP-TFII (hCOUP-TFII), which increased HNF4alpha mRNA levels in 832/13 INS-1 cells and in mouse pancreatic islets. |
| 1748 | 18474611 | Finally, hCOUP-TFII overexpression showed that there is direct COUP-TFII autorepression, as COUP-TFII occupies the proximal DR-1 binding site of its own gene in vivo. |
| 1749 | 18474611 | Therefore, COUP-TFII may contribute to the control of insulin secretion through the complex HNF4alpha/maturity-onset diabetes of the young 1 (MODY1) transcription factor network operating in beta cells. |
| 1750 | 18474611 | The MODY1 gene for hepatocyte nuclear factor 4alpha and a feedback loop control COUP-TFII expression in pancreatic beta cells. |
| 1751 | 18474611 | Knockout mice with the heterozygous deletion of the gene for chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) or the complete disruption of the gene for hepatocyte nuclear factor 4alpha (HNF4alpha) in pancreatic beta cells have similar insulin secretion defects, leading us to hypothesize that there is transcriptional cross talk between these two nuclear receptors. |
| 1752 | 18474611 | Here, we demonstrate specific HNF4alpha activation of a reporter plasmid containing the COUP-TFII gene promoter region in transfected pancreatic beta cells. |
| 1753 | 18474611 | The stable association of the endogenous HNF4alpha with a region of the COUP-TFII gene promoter that contains a direct repeat 1 (DR-1) binding site was revealed by chromatin immunoprecipitation. |
| 1754 | 18474611 | Mutation experiments showed that this DR-1 site is essential for HNF4alpha transactivation of COUP-TFII. |
| 1755 | 18474611 | The dominant negative suppression of HNF4alpha function decreased endogenous COUP-TFII expression, and the specific inactivation of COUP-TFII by small interfering RNA caused HNF4alpha mRNA levels in 832/13 INS-1 cells to decrease. |
| 1756 | 18474611 | This positive regulation of HNF4alpha by COUP-TFII was confirmed by the adenovirus-mediated overexpression of human COUP-TFII (hCOUP-TFII), which increased HNF4alpha mRNA levels in 832/13 INS-1 cells and in mouse pancreatic islets. |
| 1757 | 18474611 | Finally, hCOUP-TFII overexpression showed that there is direct COUP-TFII autorepression, as COUP-TFII occupies the proximal DR-1 binding site of its own gene in vivo. |
| 1758 | 18474611 | Therefore, COUP-TFII may contribute to the control of insulin secretion through the complex HNF4alpha/maturity-onset diabetes of the young 1 (MODY1) transcription factor network operating in beta cells. |
| 1759 | 18474611 | The MODY1 gene for hepatocyte nuclear factor 4alpha and a feedback loop control COUP-TFII expression in pancreatic beta cells. |
| 1760 | 18474611 | Knockout mice with the heterozygous deletion of the gene for chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) or the complete disruption of the gene for hepatocyte nuclear factor 4alpha (HNF4alpha) in pancreatic beta cells have similar insulin secretion defects, leading us to hypothesize that there is transcriptional cross talk between these two nuclear receptors. |
| 1761 | 18474611 | Here, we demonstrate specific HNF4alpha activation of a reporter plasmid containing the COUP-TFII gene promoter region in transfected pancreatic beta cells. |
| 1762 | 18474611 | The stable association of the endogenous HNF4alpha with a region of the COUP-TFII gene promoter that contains a direct repeat 1 (DR-1) binding site was revealed by chromatin immunoprecipitation. |
| 1763 | 18474611 | Mutation experiments showed that this DR-1 site is essential for HNF4alpha transactivation of COUP-TFII. |
| 1764 | 18474611 | The dominant negative suppression of HNF4alpha function decreased endogenous COUP-TFII expression, and the specific inactivation of COUP-TFII by small interfering RNA caused HNF4alpha mRNA levels in 832/13 INS-1 cells to decrease. |
| 1765 | 18474611 | This positive regulation of HNF4alpha by COUP-TFII was confirmed by the adenovirus-mediated overexpression of human COUP-TFII (hCOUP-TFII), which increased HNF4alpha mRNA levels in 832/13 INS-1 cells and in mouse pancreatic islets. |
| 1766 | 18474611 | Finally, hCOUP-TFII overexpression showed that there is direct COUP-TFII autorepression, as COUP-TFII occupies the proximal DR-1 binding site of its own gene in vivo. |
| 1767 | 18474611 | Therefore, COUP-TFII may contribute to the control of insulin secretion through the complex HNF4alpha/maturity-onset diabetes of the young 1 (MODY1) transcription factor network operating in beta cells. |
| 1768 | 18474611 | The MODY1 gene for hepatocyte nuclear factor 4alpha and a feedback loop control COUP-TFII expression in pancreatic beta cells. |
| 1769 | 18474611 | Knockout mice with the heterozygous deletion of the gene for chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) or the complete disruption of the gene for hepatocyte nuclear factor 4alpha (HNF4alpha) in pancreatic beta cells have similar insulin secretion defects, leading us to hypothesize that there is transcriptional cross talk between these two nuclear receptors. |
| 1770 | 18474611 | Here, we demonstrate specific HNF4alpha activation of a reporter plasmid containing the COUP-TFII gene promoter region in transfected pancreatic beta cells. |
| 1771 | 18474611 | The stable association of the endogenous HNF4alpha with a region of the COUP-TFII gene promoter that contains a direct repeat 1 (DR-1) binding site was revealed by chromatin immunoprecipitation. |
| 1772 | 18474611 | Mutation experiments showed that this DR-1 site is essential for HNF4alpha transactivation of COUP-TFII. |
| 1773 | 18474611 | The dominant negative suppression of HNF4alpha function decreased endogenous COUP-TFII expression, and the specific inactivation of COUP-TFII by small interfering RNA caused HNF4alpha mRNA levels in 832/13 INS-1 cells to decrease. |
| 1774 | 18474611 | This positive regulation of HNF4alpha by COUP-TFII was confirmed by the adenovirus-mediated overexpression of human COUP-TFII (hCOUP-TFII), which increased HNF4alpha mRNA levels in 832/13 INS-1 cells and in mouse pancreatic islets. |
| 1775 | 18474611 | Finally, hCOUP-TFII overexpression showed that there is direct COUP-TFII autorepression, as COUP-TFII occupies the proximal DR-1 binding site of its own gene in vivo. |
| 1776 | 18474611 | Therefore, COUP-TFII may contribute to the control of insulin secretion through the complex HNF4alpha/maturity-onset diabetes of the young 1 (MODY1) transcription factor network operating in beta cells. |
| 1777 | 18474611 | The MODY1 gene for hepatocyte nuclear factor 4alpha and a feedback loop control COUP-TFII expression in pancreatic beta cells. |
| 1778 | 18474611 | Knockout mice with the heterozygous deletion of the gene for chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) or the complete disruption of the gene for hepatocyte nuclear factor 4alpha (HNF4alpha) in pancreatic beta cells have similar insulin secretion defects, leading us to hypothesize that there is transcriptional cross talk between these two nuclear receptors. |
| 1779 | 18474611 | Here, we demonstrate specific HNF4alpha activation of a reporter plasmid containing the COUP-TFII gene promoter region in transfected pancreatic beta cells. |
| 1780 | 18474611 | The stable association of the endogenous HNF4alpha with a region of the COUP-TFII gene promoter that contains a direct repeat 1 (DR-1) binding site was revealed by chromatin immunoprecipitation. |
| 1781 | 18474611 | Mutation experiments showed that this DR-1 site is essential for HNF4alpha transactivation of COUP-TFII. |
| 1782 | 18474611 | The dominant negative suppression of HNF4alpha function decreased endogenous COUP-TFII expression, and the specific inactivation of COUP-TFII by small interfering RNA caused HNF4alpha mRNA levels in 832/13 INS-1 cells to decrease. |
| 1783 | 18474611 | This positive regulation of HNF4alpha by COUP-TFII was confirmed by the adenovirus-mediated overexpression of human COUP-TFII (hCOUP-TFII), which increased HNF4alpha mRNA levels in 832/13 INS-1 cells and in mouse pancreatic islets. |
| 1784 | 18474611 | Finally, hCOUP-TFII overexpression showed that there is direct COUP-TFII autorepression, as COUP-TFII occupies the proximal DR-1 binding site of its own gene in vivo. |
| 1785 | 18474611 | Therefore, COUP-TFII may contribute to the control of insulin secretion through the complex HNF4alpha/maturity-onset diabetes of the young 1 (MODY1) transcription factor network operating in beta cells. |
| 1786 | 18501722 | Further, a moderate improvement of dyslipidemia by metformin was reported, and therefore, the effect of metformin on the release of apolipoprotein B (ApoB) and ApoE in primary human hepatocytes was determined. |
| 1787 | 18501722 | Metformin at 0.5 and 1 mM reduced hepatic ApoB secretion but ApoE was not altered. |
| 1788 | 18501722 | Metformin is well known to stimulate the AMP kinase that subsequently reduces hepatic nuclear factor 4-alpha (HNF4-alpha) and HNF4-alpha regulated genes like ApoB. |
| 1789 | 18501722 | However, HNF4-alpha was only diminished by 1 mM metformin and ApoB mRNA was not suppressed indicating that this pathway may not explain reduced ApoB release. |
| 1790 | 18501722 | Further, a moderate improvement of dyslipidemia by metformin was reported, and therefore, the effect of metformin on the release of apolipoprotein B (ApoB) and ApoE in primary human hepatocytes was determined. |
| 1791 | 18501722 | Metformin at 0.5 and 1 mM reduced hepatic ApoB secretion but ApoE was not altered. |
| 1792 | 18501722 | Metformin is well known to stimulate the AMP kinase that subsequently reduces hepatic nuclear factor 4-alpha (HNF4-alpha) and HNF4-alpha regulated genes like ApoB. |
| 1793 | 18501722 | However, HNF4-alpha was only diminished by 1 mM metformin and ApoB mRNA was not suppressed indicating that this pathway may not explain reduced ApoB release. |
| 1794 | 18504548 | It has also led to the identification of common risk variants via candidate gene approaches (e.g. the E23K polymorphism in KCNJ11 or common variants in the MODY genes), and it has been validated by the description of the robust physiological effects conferred by polymorphisms in the TCF7L2 gene. |
| 1795 | 18511845 | TGFbeta1, TNFalpha, and insulin signaling crosstalk in regulation of the rat cholesterol 7alpha-hydroxylase gene expression. |
| 1796 | 18511845 | Previous studies show that TGFbeta1, TNFalpha, and insulin inhibit cholesterol 7alpha-hydroxylase (CYP7A1) gene transcription and bile acid synthesis in human hepatocytes. |
| 1797 | 18511845 | In this study, we investigated insulin, TGFbeta1, and TNFalpha regulation of rat Cyp7a1 gene transcription. |
| 1798 | 18511845 | Smad3, FoxO1, and HNF4alpha synergistically stimulated rat Cyp7a1 gene transcription. |
| 1799 | 18511845 | Mutations of the Smad3, FoxO1, or HNF4alpha binding site attenuated the rat Cyp7a1 promoter activity. |
| 1800 | 18511845 | Furthermore, TNFalpha and cJun attenuated TGFbeta1 stimulation of rat Cyp7a1. |
| 1801 | 18511845 | Insulin or adenovirus-mediated expression of constitutively active AKT1 inhibited FoxO1 and Smad3 synergy. |
| 1802 | 18511845 | In streptozotocin-induced diabetic rats, Cyp7a1 mRNA expression levels were induced and insulin attenuated CYP7A1 mRNA levels. |
| 1803 | 18511845 | Chromatin immunoprecipitation assay showed that FoxO1 binding to Cyp7a1 chromatin was increased in diabetic rat livers and insulin reduced FoxO1 binding. |
| 1804 | 18511845 | The crosstalk of insulin, TGFbeta and TNFalpha signaling pathways may regulate bile acid synthesis and lipid homeostasis in diabetes, fatty liver disease, and liver fibrosis. |
| 1805 | 18511845 | TGFbeta1, TNFalpha, and insulin signaling crosstalk in regulation of the rat cholesterol 7alpha-hydroxylase gene expression. |
| 1806 | 18511845 | Previous studies show that TGFbeta1, TNFalpha, and insulin inhibit cholesterol 7alpha-hydroxylase (CYP7A1) gene transcription and bile acid synthesis in human hepatocytes. |
| 1807 | 18511845 | In this study, we investigated insulin, TGFbeta1, and TNFalpha regulation of rat Cyp7a1 gene transcription. |
| 1808 | 18511845 | Smad3, FoxO1, and HNF4alpha synergistically stimulated rat Cyp7a1 gene transcription. |
| 1809 | 18511845 | Mutations of the Smad3, FoxO1, or HNF4alpha binding site attenuated the rat Cyp7a1 promoter activity. |
| 1810 | 18511845 | Furthermore, TNFalpha and cJun attenuated TGFbeta1 stimulation of rat Cyp7a1. |
| 1811 | 18511845 | Insulin or adenovirus-mediated expression of constitutively active AKT1 inhibited FoxO1 and Smad3 synergy. |
| 1812 | 18511845 | In streptozotocin-induced diabetic rats, Cyp7a1 mRNA expression levels were induced and insulin attenuated CYP7A1 mRNA levels. |
| 1813 | 18511845 | Chromatin immunoprecipitation assay showed that FoxO1 binding to Cyp7a1 chromatin was increased in diabetic rat livers and insulin reduced FoxO1 binding. |
| 1814 | 18511845 | The crosstalk of insulin, TGFbeta and TNFalpha signaling pathways may regulate bile acid synthesis and lipid homeostasis in diabetes, fatty liver disease, and liver fibrosis. |
| 1815 | 18599616 | As a component of the bipartite transcription factor beta-catenin/TCF, TCF7L2 is important in conveying Wnt signaling during embryonic development and in regulating gene expression during adulthood. |
| 1816 | 18599616 | Although we still do not know mechanistically how the polymorphisms within the intron regions of TCF7L2 affect the risk of type 2 diabetes, this transcriptional regulator was shown to be involved in stimulating the proliferation of pancreatic beta-cells and the production of the incretin hormone glucagon-like peptide-1 in intestinal endocrine L cells. |
| 1817 | 18602936 | The xenobiotic-metabolizing cytochrome P450 (CYP) 2A5 enzyme has been shown to be induced by fasting and by glucagon and cyclic AMP (cAMP), which mediate numerous fasting responses. |
| 1818 | 18602936 | Chromatin immunoprecipitation assays showed that PGC-1alpha binds, together with HNF-4alpha, to the same region at the Cyp2a5 proximal promoter. |
| 1819 | 18602936 | In conclusion, PGC-1alpha mediates the expression of Cyp2a5 induced by cAMP in mouse hepatocytes through coactivation of transcription factor HNF-4alpha. |
| 1820 | 18602936 | The xenobiotic-metabolizing cytochrome P450 (CYP) 2A5 enzyme has been shown to be induced by fasting and by glucagon and cyclic AMP (cAMP), which mediate numerous fasting responses. |
| 1821 | 18602936 | Chromatin immunoprecipitation assays showed that PGC-1alpha binds, together with HNF-4alpha, to the same region at the Cyp2a5 proximal promoter. |
| 1822 | 18602936 | In conclusion, PGC-1alpha mediates the expression of Cyp2a5 induced by cAMP in mouse hepatocytes through coactivation of transcription factor HNF-4alpha. |
| 1823 | 18602983 | The most significant SNPs were found in the perigenic regions: HNF4A (hepatocyte nuclear factor 4alpha), SLC12A5 (potassium-chloride cotransporter member 5), CDH22 (cadherin-like 22), ELMO2 (engulfment and cell motility 2), SLC13A3 (sodium-dependent dicarboxylate transporter member 3), and PREX1 (phosphatidylinositol 3,4,5-triphosphate-dependent RAC exchanger 1). |
| 1824 | 18602983 | We replicated the PREX1 SNP association in an independent case-control T2DM population and inferred replication of CDH22, ELMO2, SLC13A3, SLC12A5, and PREX1 using in silico perigenic analysis of two T2DM Genome-Wide Association Study data sets. |
| 1825 | 18696049 | The major effector of the canonical WNT signalling pathway is the bipartite transcription factor beta-catenin/T cell transcription factor (beta-cat/TCF), formed by free beta-cat and one of the four TCFs. |
| 1826 | 18696049 | The WNT pathway is involved in lipid metabolism and glucose homeostasis, and mutations in LRP5 may lead to the development of diabetes and obesity. beta-Cat/TCF is also involved in the production of the incretin hormone glucagon-like peptide-1 in the intestinal endocrine L cells. |
| 1827 | 18696049 | The major effector of the canonical WNT signalling pathway is the bipartite transcription factor beta-catenin/T cell transcription factor (beta-cat/TCF), formed by free beta-cat and one of the four TCFs. |
| 1828 | 18696049 | The WNT pathway is involved in lipid metabolism and glucose homeostasis, and mutations in LRP5 may lead to the development of diabetes and obesity. beta-Cat/TCF is also involved in the production of the incretin hormone glucagon-like peptide-1 in the intestinal endocrine L cells. |
| 1829 | 18829458 | We describe here the 2.0 angstroms crystal structure of human HNF4alpha DNA binding domain in complex with a high affinity promoter element of another MODY gene, HNF1alpha, which reveals the molecular basis of unique target gene selection/recognition, DNA binding cooperativity, and dysfunction caused by diabetes-causing mutations. |
| 1830 | 18838325 | Molecular background and clinical characteristics of HNF1A MODY in a Polish population. |
| 1831 | 19169489 | HNF1alpha mutations are present in half of clinically defined MODY patients in South-Brazilian individuals. |
| 1832 | 19169489 | In the present study we investigated the relative prevalence of GCK (glucokinase) and HNF1alpha (hepatocyte nuclear factor 1alpha) mutations, the more frequent causes of MODY, in 13 South-Brazilian families with multiple cases of diabetes consistent with MODY. |
| 1833 | 19169489 | Heterozygous variants in GCK and HNF1alpha genes were observed respectively in one (7.7%), and six (46.2%) families. |
| 1834 | 19169489 | HNF1alpha mutations are present in half of clinically defined MODY patients in South-Brazilian individuals. |
| 1835 | 19169489 | In the present study we investigated the relative prevalence of GCK (glucokinase) and HNF1alpha (hepatocyte nuclear factor 1alpha) mutations, the more frequent causes of MODY, in 13 South-Brazilian families with multiple cases of diabetes consistent with MODY. |
| 1836 | 19169489 | Heterozygous variants in GCK and HNF1alpha genes were observed respectively in one (7.7%), and six (46.2%) families. |
| 1837 | 19179483 | Here, we examine the expression of hepatic HNF4alpha in two diabetic mouse models, db/db mice (type 2, insulin resistant) and streptozotocin-treated mice (type 1, insulin deficient). |
| 1838 | 19179483 | Because insulin increases the activity of sterol regulatory element-binding proteins (SREBP)-1c and -2, we also examined the effect of SREBPs on hepatic HNF4alpha gene expression and found that, like insulin, ectopic expression of SREBPs decreases the level of hepatic HNF4alpha protein and mRNA both in vitro in primary hepatocytes and in vivo in the liver of C57BL/6 mice. |
| 1839 | 19179483 | Finally, we use gel shift, chromatin immunoprecipitation, small interfering RNA, and reporter gene analysis to show that SREBP2 binds the human HNF4alpha P1 promoter and negatively regulates its expression. |
| 1840 | 19179483 | Here, we examine the expression of hepatic HNF4alpha in two diabetic mouse models, db/db mice (type 2, insulin resistant) and streptozotocin-treated mice (type 1, insulin deficient). |
| 1841 | 19179483 | Because insulin increases the activity of sterol regulatory element-binding proteins (SREBP)-1c and -2, we also examined the effect of SREBPs on hepatic HNF4alpha gene expression and found that, like insulin, ectopic expression of SREBPs decreases the level of hepatic HNF4alpha protein and mRNA both in vitro in primary hepatocytes and in vivo in the liver of C57BL/6 mice. |
| 1842 | 19179483 | Finally, we use gel shift, chromatin immunoprecipitation, small interfering RNA, and reporter gene analysis to show that SREBP2 binds the human HNF4alpha P1 promoter and negatively regulates its expression. |
| 1843 | 19179483 | Here, we examine the expression of hepatic HNF4alpha in two diabetic mouse models, db/db mice (type 2, insulin resistant) and streptozotocin-treated mice (type 1, insulin deficient). |
| 1844 | 19179483 | Because insulin increases the activity of sterol regulatory element-binding proteins (SREBP)-1c and -2, we also examined the effect of SREBPs on hepatic HNF4alpha gene expression and found that, like insulin, ectopic expression of SREBPs decreases the level of hepatic HNF4alpha protein and mRNA both in vitro in primary hepatocytes and in vivo in the liver of C57BL/6 mice. |
| 1845 | 19179483 | Finally, we use gel shift, chromatin immunoprecipitation, small interfering RNA, and reporter gene analysis to show that SREBP2 binds the human HNF4alpha P1 promoter and negatively regulates its expression. |
| 1846 | 19188435 | Functional targets of the monogenic diabetes transcription factors HNF-1alpha and HNF-4alpha are highly conserved between mice and humans. |
| 1847 | 19213833 | The expression of GPR39 is regulated by hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha, and in the present study, we addressed the importance of GPR39 for glucose homeostasis and pancreatic islets function. |
| 1848 | 19213833 | Gpr39(-/-) mice were studied in vivo, especially in respect of glucose tolerance and insulin sensitivity, and in vitro in respect of islet architecture, gene expression, and insulin secretion. |
| 1849 | 19213833 | Gpr39 was down-regulated on differentiation of the pluripotent pancreatic cell line AR42J cells toward the exocrine phenotype but was along with Pdx-1 strongly up-regulated on differentiation toward the endocrine phenotype. |
| 1850 | 19213833 | Gpr39(-/-) mice displayed normal insulin sensitivity but moderately impaired glucose tolerance both during oral and iv glucose tolerance tests, and Gpr39(-/-) mice had decreased plasma insulin response to oral glucose. |
| 1851 | 19213833 | Islet architecture was normal in the Gpr39 null mice, but expression of Pdx-1 and Hnf-1alpha was reduced. |
| 1852 | 19213833 | Isolated, perifused islets from Gpr39 null mice secreted less insulin in response to glucose stimulation than islets from wild-type littermates. |
| 1853 | 19239393 | Human HNF4alpha gene mutations cause maturity on-set diabetes of the young type 1, an autosomal dominant non-insulin-dependent diabetes mellitus. |
| 1854 | 19239393 | HNF4alpha is an orphan nuclear receptor because of which the endogenous ligand has not been firmly identified. |
| 1855 | 19239393 | Human HNF4alpha gene mutations cause maturity on-set diabetes of the young type 1, an autosomal dominant non-insulin-dependent diabetes mellitus. |
| 1856 | 19239393 | HNF4alpha is an orphan nuclear receptor because of which the endogenous ligand has not been firmly identified. |
| 1857 | 19252740 | HNF4alpha and HNF1alpha dysfunction as a molecular rational for cyclosporine induced posttransplantation diabetes mellitus. |
| 1858 | 19252740 | Furthermore, cyclosporine treatment of the insulinoma-1E cell line resulted in remarkable reduction in HNF4alpha protein and INS1 as well as INS2 gene expression, while transcript expression of HNF4alpha, apolipoprotein C2, glycerolkinase, pyruvatekinase and aldolase B was repressed in treated Caco-2 cells. |
| 1859 | 19252740 | HNF4alpha and HNF1alpha dysfunction as a molecular rational for cyclosporine induced posttransplantation diabetes mellitus. |
| 1860 | 19252740 | Furthermore, cyclosporine treatment of the insulinoma-1E cell line resulted in remarkable reduction in HNF4alpha protein and INS1 as well as INS2 gene expression, while transcript expression of HNF4alpha, apolipoprotein C2, glycerolkinase, pyruvatekinase and aldolase B was repressed in treated Caco-2 cells. |
| 1861 | 19336222 | A novel frameshift mutation attributable to 14-nucleotide insertion in hepatocyte nuclear factor-1alpha (HNF-1alpha) encoding a truncated HNF-1alpha (G554fsX556) with 76-amino acid deletion at its carboxyl terminus was identified in a Thai family with maturity-onset diabetes of the young (MODY). |
| 1862 | 19336222 | The wild-type and mutant HNF-1alpha could similarly bind to human glucose-transporter 2 (GLUT2) promoter examined by electrophoretic mobility shift assay (EMSA). |
| 1863 | 19336222 | However, the transactivation activities of mutant HNF-1alpha on human GLUT2 and rat L-type pyruvate kinase (L-PK) promoters in HeLa cells determined by luciferase reporter assay were reduced to approximately 55-60% of the wild-type protein. |
| 1864 | 19336222 | These results suggested that the functional defect of novel truncated HNF-1alpha (G554fsX556) on the transactivation of its target-gene promoters would account for the beta-cell dysfunction associated with the pathogenesis of MODY. |
| 1865 | 19336222 | A novel frameshift mutation attributable to 14-nucleotide insertion in hepatocyte nuclear factor-1alpha (HNF-1alpha) encoding a truncated HNF-1alpha (G554fsX556) with 76-amino acid deletion at its carboxyl terminus was identified in a Thai family with maturity-onset diabetes of the young (MODY). |
| 1866 | 19336222 | The wild-type and mutant HNF-1alpha could similarly bind to human glucose-transporter 2 (GLUT2) promoter examined by electrophoretic mobility shift assay (EMSA). |
| 1867 | 19336222 | However, the transactivation activities of mutant HNF-1alpha on human GLUT2 and rat L-type pyruvate kinase (L-PK) promoters in HeLa cells determined by luciferase reporter assay were reduced to approximately 55-60% of the wild-type protein. |
| 1868 | 19336222 | These results suggested that the functional defect of novel truncated HNF-1alpha (G554fsX556) on the transactivation of its target-gene promoters would account for the beta-cell dysfunction associated with the pathogenesis of MODY. |
| 1869 | 19565026 | Subtypes HNF1A and HNF4A are sensitive to sulfonylureas, however diabetes complications are common if not treated early. |
| 1870 | 19669260 | An HNF1alpha germline mutation is observed in less than 5% of HCA cases and can be associated with MODY 3 diabetes. (2) An activating beta-catenin mutation was found in 10% of HCA. |
| 1871 | 19669260 | These beta-catenin activated HCAs are observed in men and women, and specific risk factors, such as male hormone administration or glycogenosis, are associated with their development. |
| 1872 | 19669260 | Immunohistochemistry studies show that these HCAs overexpress beta-catenin (nuclear and cytoplasmic) and glutamine synthetase. |
| 1873 | 19669260 | They express serum amyloid A and C-reactive protein. |
| 1874 | 19669260 | An additional 10% of inflammatory HCAs express beta-catenin, and are also at risk of malignant transformation. (4) Currently, less than 10% of HCAs are unclassified. |
| 1875 | 19906834 | Visfatin regulates insulin secretion, insulin receptor signalling and mRNA expression of diabetes-related genes in mouse pancreatic beta-cells. |
| 1876 | 19906834 | This study investigated the effects of visfatin upon insulin secretion, insulin receptor activation and mRNA expression of key diabetes-related genes in clonal mouse pancreatic beta-cells. beta-TC6 cells were cultured in RPMI 1640 and were subsequently treated with recombinant visfatin. |
| 1877 | 19906834 | Incubation with visfatin caused significant changes in the mRNA expression of several key diabetes-related genes, including marked up-regulation of insulin (9-fold increase), hepatocyte nuclear factor (HNF)1beta (32-fold increase), HNF4alpha (16-fold increase) and nuclear factor kappaB (40-fold increase). |
| 1878 | 19906834 | Significant down-regulation was seen in angiotensin-converting enzyme (-3.73-fold) and UCP2 (-1.3-fold). |
| 1879 | 19906834 | Visfatin also caused a significant 46% increase in insulin secretion compared to control (P<0.003) at low glucose, and this increase was blocked by co-incubation with the specific nicotinamide phosphoribosyltransferase inhibitor FK866. |
| 1880 | 19906834 | Both visfatin and nicotinamide mononucleotide induced activation of both insulin receptor and extracellular signal-regulated kinase (ERK)1/2, with visfatin-induced insulin receptor/ERK1/2 activation being inhibited by FK866. |
| 1881 | 19906834 | We conclude that visfatin can significantly regulate insulin secretion, insulin receptor phosphorylation and intracellular signalling and the expression of a number of beta-cell function-associated genes in mouse beta-cells. |
| 1882 | 20079163 | Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population. |
| 1883 | 20300478 | PPAR/RXR Regulation of Fatty Acid Metabolism and Fatty Acid omega-Hydroxylase (CYP4) Isozymes: Implications for Prevention of Lipotoxicity in Fatty Liver Disease. |
| 1884 | 20300478 | How steatosis increases PPARalpha activated gene expression of fatty acid transport proteins, peroxisomal and mitochondrial fatty acid beta-oxidation and omega-oxidation of fatty acids genes regardless of whether dietary fatty acids are polyunsaturated (PUFA), monounsaturated (MUFA), or saturated (SFA) may be determined by the interplay of PPARs and HNF4alpha with the fatty acid transport proteins L-FABP and ACBP. |
| 1885 | 20300478 | In hepatic steatosis and steatohepatitis, the omega-oxidation cytochrome P450 CYP4A gene expression is increased even with reduced hepatic levels of PPARalpha. |
| 1886 | 20300478 | This strongly implies that CYP4A fatty acid omega-hydroxylase P450s may play an important role in the development of steatohepatitis. |
| 1887 | 20523905 | Epistasis of transcriptomes reveals synergism between transcriptional activators Hnf1alpha and Hnf4alpha. |
| 1888 | 20523905 | The transcription factors Hnf1alpha and Hnf4alpha control pancreatic islet beta-cell function and growth, and mutations in their genes cause closely related forms of diabetes. |
| 1889 | 20523905 | We have now exploited genetic epistasis to examine how Hnf1alpha and Hnf4alpha functionally interact in pancreatic islets. |
| 1890 | 20523905 | We integrated expression and genomic binding studies and show that the shared transcriptional phenotype of these two mutant models is linked to common direct targets, rather than to known effects of Hnf1alpha on Hnf4a gene transcription. |
| 1891 | 20523905 | Epistasis analysis with transcriptomes of single- and double-mutant islets revealed that Hnf1alpha and Hnf4alpha regulate common targets synergistically. |
| 1892 | 20523905 | These findings provide an in vivo strategy to study combinatorial gene regulation and reveal how Hnf1alpha and Hnf4alpha control a common islet-cell regulatory program that is defective in human monogenic diabetes. |
| 1893 | 20523905 | Epistasis of transcriptomes reveals synergism between transcriptional activators Hnf1alpha and Hnf4alpha. |
| 1894 | 20523905 | The transcription factors Hnf1alpha and Hnf4alpha control pancreatic islet beta-cell function and growth, and mutations in their genes cause closely related forms of diabetes. |
| 1895 | 20523905 | We have now exploited genetic epistasis to examine how Hnf1alpha and Hnf4alpha functionally interact in pancreatic islets. |
| 1896 | 20523905 | We integrated expression and genomic binding studies and show that the shared transcriptional phenotype of these two mutant models is linked to common direct targets, rather than to known effects of Hnf1alpha on Hnf4a gene transcription. |
| 1897 | 20523905 | Epistasis analysis with transcriptomes of single- and double-mutant islets revealed that Hnf1alpha and Hnf4alpha regulate common targets synergistically. |
| 1898 | 20523905 | These findings provide an in vivo strategy to study combinatorial gene regulation and reveal how Hnf1alpha and Hnf4alpha control a common islet-cell regulatory program that is defective in human monogenic diabetes. |
| 1899 | 20523905 | Epistasis of transcriptomes reveals synergism between transcriptional activators Hnf1alpha and Hnf4alpha. |
| 1900 | 20523905 | The transcription factors Hnf1alpha and Hnf4alpha control pancreatic islet beta-cell function and growth, and mutations in their genes cause closely related forms of diabetes. |
| 1901 | 20523905 | We have now exploited genetic epistasis to examine how Hnf1alpha and Hnf4alpha functionally interact in pancreatic islets. |
| 1902 | 20523905 | We integrated expression and genomic binding studies and show that the shared transcriptional phenotype of these two mutant models is linked to common direct targets, rather than to known effects of Hnf1alpha on Hnf4a gene transcription. |
| 1903 | 20523905 | Epistasis analysis with transcriptomes of single- and double-mutant islets revealed that Hnf1alpha and Hnf4alpha regulate common targets synergistically. |
| 1904 | 20523905 | These findings provide an in vivo strategy to study combinatorial gene regulation and reveal how Hnf1alpha and Hnf4alpha control a common islet-cell regulatory program that is defective in human monogenic diabetes. |
| 1905 | 20523905 | Epistasis of transcriptomes reveals synergism between transcriptional activators Hnf1alpha and Hnf4alpha. |
| 1906 | 20523905 | The transcription factors Hnf1alpha and Hnf4alpha control pancreatic islet beta-cell function and growth, and mutations in their genes cause closely related forms of diabetes. |
| 1907 | 20523905 | We have now exploited genetic epistasis to examine how Hnf1alpha and Hnf4alpha functionally interact in pancreatic islets. |
| 1908 | 20523905 | We integrated expression and genomic binding studies and show that the shared transcriptional phenotype of these two mutant models is linked to common direct targets, rather than to known effects of Hnf1alpha on Hnf4a gene transcription. |
| 1909 | 20523905 | Epistasis analysis with transcriptomes of single- and double-mutant islets revealed that Hnf1alpha and Hnf4alpha regulate common targets synergistically. |
| 1910 | 20523905 | These findings provide an in vivo strategy to study combinatorial gene regulation and reveal how Hnf1alpha and Hnf4alpha control a common islet-cell regulatory program that is defective in human monogenic diabetes. |
| 1911 | 20523905 | Epistasis of transcriptomes reveals synergism between transcriptional activators Hnf1alpha and Hnf4alpha. |
| 1912 | 20523905 | The transcription factors Hnf1alpha and Hnf4alpha control pancreatic islet beta-cell function and growth, and mutations in their genes cause closely related forms of diabetes. |
| 1913 | 20523905 | We have now exploited genetic epistasis to examine how Hnf1alpha and Hnf4alpha functionally interact in pancreatic islets. |
| 1914 | 20523905 | We integrated expression and genomic binding studies and show that the shared transcriptional phenotype of these two mutant models is linked to common direct targets, rather than to known effects of Hnf1alpha on Hnf4a gene transcription. |
| 1915 | 20523905 | Epistasis analysis with transcriptomes of single- and double-mutant islets revealed that Hnf1alpha and Hnf4alpha regulate common targets synergistically. |
| 1916 | 20523905 | These findings provide an in vivo strategy to study combinatorial gene regulation and reveal how Hnf1alpha and Hnf4alpha control a common islet-cell regulatory program that is defective in human monogenic diabetes. |
| 1917 | 20523905 | Epistasis of transcriptomes reveals synergism between transcriptional activators Hnf1alpha and Hnf4alpha. |
| 1918 | 20523905 | The transcription factors Hnf1alpha and Hnf4alpha control pancreatic islet beta-cell function and growth, and mutations in their genes cause closely related forms of diabetes. |
| 1919 | 20523905 | We have now exploited genetic epistasis to examine how Hnf1alpha and Hnf4alpha functionally interact in pancreatic islets. |
| 1920 | 20523905 | We integrated expression and genomic binding studies and show that the shared transcriptional phenotype of these two mutant models is linked to common direct targets, rather than to known effects of Hnf1alpha on Hnf4a gene transcription. |
| 1921 | 20523905 | Epistasis analysis with transcriptomes of single- and double-mutant islets revealed that Hnf1alpha and Hnf4alpha regulate common targets synergistically. |
| 1922 | 20523905 | These findings provide an in vivo strategy to study combinatorial gene regulation and reveal how Hnf1alpha and Hnf4alpha control a common islet-cell regulatory program that is defective in human monogenic diabetes. |
| 1923 | 20558840 | As a key regulator of insulin secretion and metabolism of glucose, cholesterol and fatty acid, hepatocyte nuclear factor 4alpha (HNF4A) was suggested as a candidate gene for type 2 diabetes (T2D); however, no association study between HNF4A and T2D in the Chinese population has been conducted before. |
| 1924 | 20660599 | Overexpression via adenovirus-mediated gene transfer and siRNA-mediated gene silencing established that hepatocyte nuclear factor 4 (HNF-4) is an important regulator of apoM gene transcription in hepatic cells. apoM promoter deletion analysis combined with DNA affinity precipitation and chromatin immunoprecipitation assays revealed that HNF-4 binds to a hormone-response element (HRE) in the proximal apoM promoter (nucleotides -33 to -21). |
| 1925 | 20660599 | Mutagenesis of this HRE decreased basal hepatic apoM promoter activity to 10% of control and abolished the HNF4-mediated transactivation of the apoM promoter. |
| 1926 | 20660599 | In addition to HNF-4, homodimers of retinoid X receptor and heterodimers of retinoid X receptor with receptors for retinoic acid, thyroid hormone, fibrates (peroxisome proliferator-activated receptor), and oxysterols (liver X receptor) were shown to bind with different affinities to the proximal HRE in vitro and in vivo. |
| 1927 | 20660599 | Overexpression via adenovirus-mediated gene transfer and siRNA-mediated gene silencing established that hepatocyte nuclear factor 4 (HNF-4) is an important regulator of apoM gene transcription in hepatic cells. apoM promoter deletion analysis combined with DNA affinity precipitation and chromatin immunoprecipitation assays revealed that HNF-4 binds to a hormone-response element (HRE) in the proximal apoM promoter (nucleotides -33 to -21). |
| 1928 | 20660599 | Mutagenesis of this HRE decreased basal hepatic apoM promoter activity to 10% of control and abolished the HNF4-mediated transactivation of the apoM promoter. |
| 1929 | 20660599 | In addition to HNF-4, homodimers of retinoid X receptor and heterodimers of retinoid X receptor with receptors for retinoic acid, thyroid hormone, fibrates (peroxisome proliferator-activated receptor), and oxysterols (liver X receptor) were shown to bind with different affinities to the proximal HRE in vitro and in vivo. |
| 1930 | 20660599 | Overexpression via adenovirus-mediated gene transfer and siRNA-mediated gene silencing established that hepatocyte nuclear factor 4 (HNF-4) is an important regulator of apoM gene transcription in hepatic cells. apoM promoter deletion analysis combined with DNA affinity precipitation and chromatin immunoprecipitation assays revealed that HNF-4 binds to a hormone-response element (HRE) in the proximal apoM promoter (nucleotides -33 to -21). |
| 1931 | 20660599 | Mutagenesis of this HRE decreased basal hepatic apoM promoter activity to 10% of control and abolished the HNF4-mediated transactivation of the apoM promoter. |
| 1932 | 20660599 | In addition to HNF-4, homodimers of retinoid X receptor and heterodimers of retinoid X receptor with receptors for retinoic acid, thyroid hormone, fibrates (peroxisome proliferator-activated receptor), and oxysterols (liver X receptor) were shown to bind with different affinities to the proximal HRE in vitro and in vivo. |
| 1933 | 20675304 | Insulin treatment and high-fat diet feeding reduces the expression of three Tcf genes in rodent pancreas. |
| 1934 | 20675304 | Both Tcf7 and Tcf7l1, but not Lef1, were expressed in the pancreas. |
| 1935 | 20675304 | The expression of the three Tcf genes (Tcf7, Tcf7l1, and Tcf7l2) in the pancreas was reduced by treatment with insulin or high-fat diet feeding, in contrast to the stimulation of Tcf7l2 expression by insulin in the gut. |
| 1936 | 20675304 | Insulin treatment and high-fat diet feeding reduces the expression of three Tcf genes in rodent pancreas. |
| 1937 | 20675304 | Both Tcf7 and Tcf7l1, but not Lef1, were expressed in the pancreas. |
| 1938 | 20675304 | The expression of the three Tcf genes (Tcf7, Tcf7l1, and Tcf7l2) in the pancreas was reduced by treatment with insulin or high-fat diet feeding, in contrast to the stimulation of Tcf7l2 expression by insulin in the gut. |
| 1939 | 20690076 | The most common cause of Maturity-Onset Diabetes of the Young (MODY) are mutations in the Hepatic Nuclear Factor 1α (HNF-1α) gene, resulting in MODY3. |
| 1940 | 20705777 | Double heterozygous mutations involving both HNF1A/MODY3 and HNF4A/MODY1 genes: a case report. |
| 1941 | 20879971 | These genes include glucokinase (GCK), HLA antigens, insulin receptor (INSR), insulin-like growth factor-2 (IGF2), HNF4A, insulin gene (INS-VNTR), plasminogen activator inhibitor 1 (PAI-1), potassium inwardly rectifying channel subfamily J, member 11 (KCNJ11), hepatocyte nuclear factor-4a (HNF4A). |
| 1942 | 21115832 | Here, we identify 9cRA in mouse pancreas by liquid chromatography/tandem mass spectrometry (LC/MS/MS), and show that 9cRA decreases with feeding and after glucose dosing and varies inversely with serum insulin. 9cRA reduces glucose-stimulated insulin secretion (GSIS) in mouse islets and in the rat β-cell line 832/13 within 15 min by reducing glucose transporter type 2 (Glut2) and glucokinase (GK) activities. 9cRA also reduces Pdx-1 and HNF4α mRNA expression, ∼8- and 80-fold, respectively: defects in Pdx-1 or HNF4α cause maturity onset diabetes of the young (MODY4 and 1, respectively), as does a defective GK gene (MODY2). |
| 1943 | 21237163 | CCN2 stimulates phosphorylation of LRP6 and GSK-3β resulting in accumulation and nuclear localisation of β-catenin, TCF/LEF activity and expression of Wnt targets. |
| 1944 | 21237163 | DKK-1 and LRP6 siRNA reversed CCN2's effects. |
| 1945 | 21263211 | Paired-homeodomain transcription factor 4 (PAX4) functions as a transcriptional repressor and is involved in the differentiation of insulin-secreting β-cells. |
| 1946 | 21263211 | Here we identified a novel PAX4 mutation in a Japanese patient with MODY. |
| 1947 | 21263211 | We therefore analyzed several candidate genes of MODY, and identified a novel mutation of a 39-base heterozygous deletion in exon 3 (c.374-412 del39) of PAX4 in the proband and his father. |
| 1948 | 21263211 | As expected, luciferase-reporter assays revealed that the mutant PAX4 could not repress the activities of insulin and glucagon gene promoters, unlike the wild-type PAX4 that repressed the promoter activities. |
| 1949 | 21263211 | Paired-homeodomain transcription factor 4 (PAX4) functions as a transcriptional repressor and is involved in the differentiation of insulin-secreting β-cells. |
| 1950 | 21263211 | Here we identified a novel PAX4 mutation in a Japanese patient with MODY. |
| 1951 | 21263211 | We therefore analyzed several candidate genes of MODY, and identified a novel mutation of a 39-base heterozygous deletion in exon 3 (c.374-412 del39) of PAX4 in the proband and his father. |
| 1952 | 21263211 | As expected, luciferase-reporter assays revealed that the mutant PAX4 could not repress the activities of insulin and glucagon gene promoters, unlike the wild-type PAX4 that repressed the promoter activities. |
| 1953 | 21300624 | Amongst these are multiple genes involved in IL23/Th17 signalling (IL23R, IL12B, JAK2, TYK2 and STAT3), IL10, IL1R2, REL, CARD9, NKX2.3, ICOSLG, PRDM1, SMAD3 and ORMDL3. |
| 1954 | 21300624 | For Crohn's disease, defective processing of intracellular bacteria has become a central theme, following gene discoveries in autophagy and innate immunity (associations with NOD2, IRGM, ATG16L1 are specific to Crohn's disease). |
| 1955 | 21300624 | Genetic evidence has also demonstrated the importance of barrier function to the development of ulcerative colitis (HNF4A, LAMB1, CDH1 and GNA12). |
| 1956 | 21442235 | Association analyses between the genetic polymorphisms of HNF4A and FOXO1 genes and Chinese Han patients with type 2 diabetes. |
| 1957 | 21442235 | The hepatocyte nuclear factor 4-alpha (HNF4A) and human forkhead box O1 (FOXO1) genes have been discovered to be associated with type 2 diabetes (T2D) in different populations. |
| 1958 | 21442235 | This study aimed to evaluate the association between HNF4A and FOXO1 genetic polymorphisms and type 2 diabetes in the Chinese Han population. |
| 1959 | 21442235 | Six single-nucleotide polymorphisms (SNPs) in HNF4A and seven in FOXO1 were selected and genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan(®) technology. |
| 1960 | 21442235 | Moreover, the authors confirmed the results of previous studies for the interaction between HNF4A and FOXO1 in the pathogenesis of type 2 diabetes. |
| 1961 | 21442235 | Association analyses between the genetic polymorphisms of HNF4A and FOXO1 genes and Chinese Han patients with type 2 diabetes. |
| 1962 | 21442235 | The hepatocyte nuclear factor 4-alpha (HNF4A) and human forkhead box O1 (FOXO1) genes have been discovered to be associated with type 2 diabetes (T2D) in different populations. |
| 1963 | 21442235 | This study aimed to evaluate the association between HNF4A and FOXO1 genetic polymorphisms and type 2 diabetes in the Chinese Han population. |
| 1964 | 21442235 | Six single-nucleotide polymorphisms (SNPs) in HNF4A and seven in FOXO1 were selected and genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan(®) technology. |
| 1965 | 21442235 | Moreover, the authors confirmed the results of previous studies for the interaction between HNF4A and FOXO1 in the pathogenesis of type 2 diabetes. |
| 1966 | 21442235 | Association analyses between the genetic polymorphisms of HNF4A and FOXO1 genes and Chinese Han patients with type 2 diabetes. |
| 1967 | 21442235 | The hepatocyte nuclear factor 4-alpha (HNF4A) and human forkhead box O1 (FOXO1) genes have been discovered to be associated with type 2 diabetes (T2D) in different populations. |
| 1968 | 21442235 | This study aimed to evaluate the association between HNF4A and FOXO1 genetic polymorphisms and type 2 diabetes in the Chinese Han population. |
| 1969 | 21442235 | Six single-nucleotide polymorphisms (SNPs) in HNF4A and seven in FOXO1 were selected and genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan(®) technology. |
| 1970 | 21442235 | Moreover, the authors confirmed the results of previous studies for the interaction between HNF4A and FOXO1 in the pathogenesis of type 2 diabetes. |
| 1971 | 21442235 | Association analyses between the genetic polymorphisms of HNF4A and FOXO1 genes and Chinese Han patients with type 2 diabetes. |
| 1972 | 21442235 | The hepatocyte nuclear factor 4-alpha (HNF4A) and human forkhead box O1 (FOXO1) genes have been discovered to be associated with type 2 diabetes (T2D) in different populations. |
| 1973 | 21442235 | This study aimed to evaluate the association between HNF4A and FOXO1 genetic polymorphisms and type 2 diabetes in the Chinese Han population. |
| 1974 | 21442235 | Six single-nucleotide polymorphisms (SNPs) in HNF4A and seven in FOXO1 were selected and genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan(®) technology. |
| 1975 | 21442235 | Moreover, the authors confirmed the results of previous studies for the interaction between HNF4A and FOXO1 in the pathogenesis of type 2 diabetes. |
| 1976 | 21442235 | Association analyses between the genetic polymorphisms of HNF4A and FOXO1 genes and Chinese Han patients with type 2 diabetes. |
| 1977 | 21442235 | The hepatocyte nuclear factor 4-alpha (HNF4A) and human forkhead box O1 (FOXO1) genes have been discovered to be associated with type 2 diabetes (T2D) in different populations. |
| 1978 | 21442235 | This study aimed to evaluate the association between HNF4A and FOXO1 genetic polymorphisms and type 2 diabetes in the Chinese Han population. |
| 1979 | 21442235 | Six single-nucleotide polymorphisms (SNPs) in HNF4A and seven in FOXO1 were selected and genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan(®) technology. |
| 1980 | 21442235 | Moreover, the authors confirmed the results of previous studies for the interaction between HNF4A and FOXO1 in the pathogenesis of type 2 diabetes. |
| 1981 | 21633728 | Hepatocyte nuclear factor 4 alpha P2 promoter variants associate with insulin resistance. |
| 1982 | 21633728 | This study aimed to investigate the associations of hepatocyte nuclear factor 4 (HNF4) alpha single nucleotide polymorphisms (SNPs) and haplotype with insulin resistance and metabolic syndrome parameters. |
| 1983 | 21633728 | The HNF4 alpha P2 promoter SNPs rs4810424, rs1884613 and rs1884614 were associated with insulin resistance (p = 0.017; 0.037; 0.024) and body mass index (BMI) (p = 0.03; 0.035; 0.039). |
| 1984 | 21633728 | HNF4 alpha common haplotype CCCGTC associated with higher insulin resistance (p = 0.022), fasting blood glucose (FBG) (p = 0.035) and lower HDLc (p = 0.001). |
| 1985 | 21633728 | In conclusion, subjects with HNF4 alpha P2 variants and haplotypes have been shown to have a higher insulin resistance and are therefore at a higher risk for developing type 2 diabetes mellitus. |
| 1986 | 21633728 | Hepatocyte nuclear factor 4 alpha P2 promoter variants associate with insulin resistance. |
| 1987 | 21633728 | This study aimed to investigate the associations of hepatocyte nuclear factor 4 (HNF4) alpha single nucleotide polymorphisms (SNPs) and haplotype with insulin resistance and metabolic syndrome parameters. |
| 1988 | 21633728 | The HNF4 alpha P2 promoter SNPs rs4810424, rs1884613 and rs1884614 were associated with insulin resistance (p = 0.017; 0.037; 0.024) and body mass index (BMI) (p = 0.03; 0.035; 0.039). |
| 1989 | 21633728 | HNF4 alpha common haplotype CCCGTC associated with higher insulin resistance (p = 0.022), fasting blood glucose (FBG) (p = 0.035) and lower HDLc (p = 0.001). |
| 1990 | 21633728 | In conclusion, subjects with HNF4 alpha P2 variants and haplotypes have been shown to have a higher insulin resistance and are therefore at a higher risk for developing type 2 diabetes mellitus. |
| 1991 | 21633728 | Hepatocyte nuclear factor 4 alpha P2 promoter variants associate with insulin resistance. |
| 1992 | 21633728 | This study aimed to investigate the associations of hepatocyte nuclear factor 4 (HNF4) alpha single nucleotide polymorphisms (SNPs) and haplotype with insulin resistance and metabolic syndrome parameters. |
| 1993 | 21633728 | The HNF4 alpha P2 promoter SNPs rs4810424, rs1884613 and rs1884614 were associated with insulin resistance (p = 0.017; 0.037; 0.024) and body mass index (BMI) (p = 0.03; 0.035; 0.039). |
| 1994 | 21633728 | HNF4 alpha common haplotype CCCGTC associated with higher insulin resistance (p = 0.022), fasting blood glucose (FBG) (p = 0.035) and lower HDLc (p = 0.001). |
| 1995 | 21633728 | In conclusion, subjects with HNF4 alpha P2 variants and haplotypes have been shown to have a higher insulin resistance and are therefore at a higher risk for developing type 2 diabetes mellitus. |
| 1996 | 21633728 | Hepatocyte nuclear factor 4 alpha P2 promoter variants associate with insulin resistance. |
| 1997 | 21633728 | This study aimed to investigate the associations of hepatocyte nuclear factor 4 (HNF4) alpha single nucleotide polymorphisms (SNPs) and haplotype with insulin resistance and metabolic syndrome parameters. |
| 1998 | 21633728 | The HNF4 alpha P2 promoter SNPs rs4810424, rs1884613 and rs1884614 were associated with insulin resistance (p = 0.017; 0.037; 0.024) and body mass index (BMI) (p = 0.03; 0.035; 0.039). |
| 1999 | 21633728 | HNF4 alpha common haplotype CCCGTC associated with higher insulin resistance (p = 0.022), fasting blood glucose (FBG) (p = 0.035) and lower HDLc (p = 0.001). |
| 2000 | 21633728 | In conclusion, subjects with HNF4 alpha P2 variants and haplotypes have been shown to have a higher insulin resistance and are therefore at a higher risk for developing type 2 diabetes mellitus. |
| 2001 | 21633728 | Hepatocyte nuclear factor 4 alpha P2 promoter variants associate with insulin resistance. |
| 2002 | 21633728 | This study aimed to investigate the associations of hepatocyte nuclear factor 4 (HNF4) alpha single nucleotide polymorphisms (SNPs) and haplotype with insulin resistance and metabolic syndrome parameters. |
| 2003 | 21633728 | The HNF4 alpha P2 promoter SNPs rs4810424, rs1884613 and rs1884614 were associated with insulin resistance (p = 0.017; 0.037; 0.024) and body mass index (BMI) (p = 0.03; 0.035; 0.039). |
| 2004 | 21633728 | HNF4 alpha common haplotype CCCGTC associated with higher insulin resistance (p = 0.022), fasting blood glucose (FBG) (p = 0.035) and lower HDLc (p = 0.001). |
| 2005 | 21633728 | In conclusion, subjects with HNF4 alpha P2 variants and haplotypes have been shown to have a higher insulin resistance and are therefore at a higher risk for developing type 2 diabetes mellitus. |
| 2006 | 21677915 | This is followed by a discussion on the glucokinase and hepatocyte nuclear factor-1 alpha MODY, which together constitute the most frequent cause of MODY syndromes in all populations. |
| 2007 | 21761282 | Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection. |
| 2008 | 21761282 | The aim of this study was to evaluate the beta cell and incretin function in patients with HNF4A and HNF1A MODY during a test meal. |
| 2009 | 21761282 | Clinical characteristics and biochemical data (glucose, proinsulin, insulin, C-peptide, GLP-1 and GIP) during a test meal were compared between MODY patients from eight different families. |
| 2010 | 21761282 | The early phase of insulin secretion was attenuated in HNF4A, HNF1A MODY and T2D (AUC0-30 controls: 558.2 ± 101.2, HNF4A MODY: 93.8 ± 57.0, HNF1A MODY: 170.2 ± 64.5, T2D: 211.2 ± 65.3, P < 0.01). |
| 2011 | 21761282 | Markedly reduced levels of proinsulin were found in HNF4A MODY compared to T2D and that tended to be so also in HNF1A MODY (HNF4A MODY: 3.7 ± 1.2, HNF1A MODY: 8.3 ± 3.8 vs. |
| 2012 | 21761282 | Patients with HNF4A MODY had similar total GLP-1 and GIP responses as controls (GLP-1 AUC: (control: 823.9 ± 703.8, T2D: 556.4 ± 698.2, HNF4A MODY: 1,257.0 ± 999.3, HNF1A MODY: 697.1 ± 818.4) but with a different secretion pattern. |
| 2013 | 21761282 | Patients with HNF4A and HNF1A MODY showed an attenuated early phase of insulin secretion similar to T2Ds. |
| 2014 | 21761282 | Thus, GIP may be a more important factor for insulin secretion than GLP-1 in MODY patients. |
| 2015 | 21761282 | Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection. |
| 2016 | 21761282 | The aim of this study was to evaluate the beta cell and incretin function in patients with HNF4A and HNF1A MODY during a test meal. |
| 2017 | 21761282 | Clinical characteristics and biochemical data (glucose, proinsulin, insulin, C-peptide, GLP-1 and GIP) during a test meal were compared between MODY patients from eight different families. |
| 2018 | 21761282 | The early phase of insulin secretion was attenuated in HNF4A, HNF1A MODY and T2D (AUC0-30 controls: 558.2 ± 101.2, HNF4A MODY: 93.8 ± 57.0, HNF1A MODY: 170.2 ± 64.5, T2D: 211.2 ± 65.3, P < 0.01). |
| 2019 | 21761282 | Markedly reduced levels of proinsulin were found in HNF4A MODY compared to T2D and that tended to be so also in HNF1A MODY (HNF4A MODY: 3.7 ± 1.2, HNF1A MODY: 8.3 ± 3.8 vs. |
| 2020 | 21761282 | Patients with HNF4A MODY had similar total GLP-1 and GIP responses as controls (GLP-1 AUC: (control: 823.9 ± 703.8, T2D: 556.4 ± 698.2, HNF4A MODY: 1,257.0 ± 999.3, HNF1A MODY: 697.1 ± 818.4) but with a different secretion pattern. |
| 2021 | 21761282 | Patients with HNF4A and HNF1A MODY showed an attenuated early phase of insulin secretion similar to T2Ds. |
| 2022 | 21761282 | Thus, GIP may be a more important factor for insulin secretion than GLP-1 in MODY patients. |
| 2023 | 21761282 | Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection. |
| 2024 | 21761282 | The aim of this study was to evaluate the beta cell and incretin function in patients with HNF4A and HNF1A MODY during a test meal. |
| 2025 | 21761282 | Clinical characteristics and biochemical data (glucose, proinsulin, insulin, C-peptide, GLP-1 and GIP) during a test meal were compared between MODY patients from eight different families. |
| 2026 | 21761282 | The early phase of insulin secretion was attenuated in HNF4A, HNF1A MODY and T2D (AUC0-30 controls: 558.2 ± 101.2, HNF4A MODY: 93.8 ± 57.0, HNF1A MODY: 170.2 ± 64.5, T2D: 211.2 ± 65.3, P < 0.01). |
| 2027 | 21761282 | Markedly reduced levels of proinsulin were found in HNF4A MODY compared to T2D and that tended to be so also in HNF1A MODY (HNF4A MODY: 3.7 ± 1.2, HNF1A MODY: 8.3 ± 3.8 vs. |
| 2028 | 21761282 | Patients with HNF4A MODY had similar total GLP-1 and GIP responses as controls (GLP-1 AUC: (control: 823.9 ± 703.8, T2D: 556.4 ± 698.2, HNF4A MODY: 1,257.0 ± 999.3, HNF1A MODY: 697.1 ± 818.4) but with a different secretion pattern. |
| 2029 | 21761282 | Patients with HNF4A and HNF1A MODY showed an attenuated early phase of insulin secretion similar to T2Ds. |
| 2030 | 21761282 | Thus, GIP may be a more important factor for insulin secretion than GLP-1 in MODY patients. |
| 2031 | 21761282 | Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection. |
| 2032 | 21761282 | The aim of this study was to evaluate the beta cell and incretin function in patients with HNF4A and HNF1A MODY during a test meal. |
| 2033 | 21761282 | Clinical characteristics and biochemical data (glucose, proinsulin, insulin, C-peptide, GLP-1 and GIP) during a test meal were compared between MODY patients from eight different families. |
| 2034 | 21761282 | The early phase of insulin secretion was attenuated in HNF4A, HNF1A MODY and T2D (AUC0-30 controls: 558.2 ± 101.2, HNF4A MODY: 93.8 ± 57.0, HNF1A MODY: 170.2 ± 64.5, T2D: 211.2 ± 65.3, P < 0.01). |
| 2035 | 21761282 | Markedly reduced levels of proinsulin were found in HNF4A MODY compared to T2D and that tended to be so also in HNF1A MODY (HNF4A MODY: 3.7 ± 1.2, HNF1A MODY: 8.3 ± 3.8 vs. |
| 2036 | 21761282 | Patients with HNF4A MODY had similar total GLP-1 and GIP responses as controls (GLP-1 AUC: (control: 823.9 ± 703.8, T2D: 556.4 ± 698.2, HNF4A MODY: 1,257.0 ± 999.3, HNF1A MODY: 697.1 ± 818.4) but with a different secretion pattern. |
| 2037 | 21761282 | Patients with HNF4A and HNF1A MODY showed an attenuated early phase of insulin secretion similar to T2Ds. |
| 2038 | 21761282 | Thus, GIP may be a more important factor for insulin secretion than GLP-1 in MODY patients. |
| 2039 | 21761282 | Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection. |
| 2040 | 21761282 | The aim of this study was to evaluate the beta cell and incretin function in patients with HNF4A and HNF1A MODY during a test meal. |
| 2041 | 21761282 | Clinical characteristics and biochemical data (glucose, proinsulin, insulin, C-peptide, GLP-1 and GIP) during a test meal were compared between MODY patients from eight different families. |
| 2042 | 21761282 | The early phase of insulin secretion was attenuated in HNF4A, HNF1A MODY and T2D (AUC0-30 controls: 558.2 ± 101.2, HNF4A MODY: 93.8 ± 57.0, HNF1A MODY: 170.2 ± 64.5, T2D: 211.2 ± 65.3, P < 0.01). |
| 2043 | 21761282 | Markedly reduced levels of proinsulin were found in HNF4A MODY compared to T2D and that tended to be so also in HNF1A MODY (HNF4A MODY: 3.7 ± 1.2, HNF1A MODY: 8.3 ± 3.8 vs. |
| 2044 | 21761282 | Patients with HNF4A MODY had similar total GLP-1 and GIP responses as controls (GLP-1 AUC: (control: 823.9 ± 703.8, T2D: 556.4 ± 698.2, HNF4A MODY: 1,257.0 ± 999.3, HNF1A MODY: 697.1 ± 818.4) but with a different secretion pattern. |
| 2045 | 21761282 | Patients with HNF4A and HNF1A MODY showed an attenuated early phase of insulin secretion similar to T2Ds. |
| 2046 | 21761282 | Thus, GIP may be a more important factor for insulin secretion than GLP-1 in MODY patients. |
| 2047 | 21761282 | Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection. |
| 2048 | 21761282 | The aim of this study was to evaluate the beta cell and incretin function in patients with HNF4A and HNF1A MODY during a test meal. |
| 2049 | 21761282 | Clinical characteristics and biochemical data (glucose, proinsulin, insulin, C-peptide, GLP-1 and GIP) during a test meal were compared between MODY patients from eight different families. |
| 2050 | 21761282 | The early phase of insulin secretion was attenuated in HNF4A, HNF1A MODY and T2D (AUC0-30 controls: 558.2 ± 101.2, HNF4A MODY: 93.8 ± 57.0, HNF1A MODY: 170.2 ± 64.5, T2D: 211.2 ± 65.3, P < 0.01). |
| 2051 | 21761282 | Markedly reduced levels of proinsulin were found in HNF4A MODY compared to T2D and that tended to be so also in HNF1A MODY (HNF4A MODY: 3.7 ± 1.2, HNF1A MODY: 8.3 ± 3.8 vs. |
| 2052 | 21761282 | Patients with HNF4A MODY had similar total GLP-1 and GIP responses as controls (GLP-1 AUC: (control: 823.9 ± 703.8, T2D: 556.4 ± 698.2, HNF4A MODY: 1,257.0 ± 999.3, HNF1A MODY: 697.1 ± 818.4) but with a different secretion pattern. |
| 2053 | 21761282 | Patients with HNF4A and HNF1A MODY showed an attenuated early phase of insulin secretion similar to T2Ds. |
| 2054 | 21761282 | Thus, GIP may be a more important factor for insulin secretion than GLP-1 in MODY patients. |
| 2055 | 21761282 | Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection. |
| 2056 | 21761282 | The aim of this study was to evaluate the beta cell and incretin function in patients with HNF4A and HNF1A MODY during a test meal. |
| 2057 | 21761282 | Clinical characteristics and biochemical data (glucose, proinsulin, insulin, C-peptide, GLP-1 and GIP) during a test meal were compared between MODY patients from eight different families. |
| 2058 | 21761282 | The early phase of insulin secretion was attenuated in HNF4A, HNF1A MODY and T2D (AUC0-30 controls: 558.2 ± 101.2, HNF4A MODY: 93.8 ± 57.0, HNF1A MODY: 170.2 ± 64.5, T2D: 211.2 ± 65.3, P < 0.01). |
| 2059 | 21761282 | Markedly reduced levels of proinsulin were found in HNF4A MODY compared to T2D and that tended to be so also in HNF1A MODY (HNF4A MODY: 3.7 ± 1.2, HNF1A MODY: 8.3 ± 3.8 vs. |
| 2060 | 21761282 | Patients with HNF4A MODY had similar total GLP-1 and GIP responses as controls (GLP-1 AUC: (control: 823.9 ± 703.8, T2D: 556.4 ± 698.2, HNF4A MODY: 1,257.0 ± 999.3, HNF1A MODY: 697.1 ± 818.4) but with a different secretion pattern. |
| 2061 | 21761282 | Patients with HNF4A and HNF1A MODY showed an attenuated early phase of insulin secretion similar to T2Ds. |
| 2062 | 21761282 | Thus, GIP may be a more important factor for insulin secretion than GLP-1 in MODY patients. |
| 2063 | 21761282 | Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection. |
| 2064 | 21761282 | The aim of this study was to evaluate the beta cell and incretin function in patients with HNF4A and HNF1A MODY during a test meal. |
| 2065 | 21761282 | Clinical characteristics and biochemical data (glucose, proinsulin, insulin, C-peptide, GLP-1 and GIP) during a test meal were compared between MODY patients from eight different families. |
| 2066 | 21761282 | The early phase of insulin secretion was attenuated in HNF4A, HNF1A MODY and T2D (AUC0-30 controls: 558.2 ± 101.2, HNF4A MODY: 93.8 ± 57.0, HNF1A MODY: 170.2 ± 64.5, T2D: 211.2 ± 65.3, P < 0.01). |
| 2067 | 21761282 | Markedly reduced levels of proinsulin were found in HNF4A MODY compared to T2D and that tended to be so also in HNF1A MODY (HNF4A MODY: 3.7 ± 1.2, HNF1A MODY: 8.3 ± 3.8 vs. |
| 2068 | 21761282 | Patients with HNF4A MODY had similar total GLP-1 and GIP responses as controls (GLP-1 AUC: (control: 823.9 ± 703.8, T2D: 556.4 ± 698.2, HNF4A MODY: 1,257.0 ± 999.3, HNF1A MODY: 697.1 ± 818.4) but with a different secretion pattern. |
| 2069 | 21761282 | Patients with HNF4A and HNF1A MODY showed an attenuated early phase of insulin secretion similar to T2Ds. |
| 2070 | 21761282 | Thus, GIP may be a more important factor for insulin secretion than GLP-1 in MODY patients. |
| 2071 | 21768169 | Potential role of estradiol and progesterone in insulin resistance through constitutive androstane receptor. |
| 2072 | 21768169 | The constitutive androstane receptor (CAR) may participate in insulin resistance in pregnancy, and sex steroids, estradiol (E(2)) and progesterone, may also be involved. |
| 2073 | 21768169 | DNA affinity immunoblotting and chromatin immunoprecipitation assay revealed that CAR ligand enhanced the recruitment of the gluconeogenic transcription factors, forkhead box O1 (FOXO1) and hepatocyte nuclear factor 4α (HNF4α), but sex steroids suppressed these recruitments on the CAR responsive element. |
| 2074 | 21814221 | We genotyped 91 polymorphisms in 19 genes (ABCC8, HNF1A, HNF1B, HNF4A, INS, INSM1, ISL1, KCNJ11, MAFA, MNX1, NEUROD1, NEUROG3, NKX2.2, NKX6.1, PAX4, PAX6, PDX1, USF1 and WFS1) in 2025 unrelated North Indians of Indo-European ethnicity comprising of 1019 diabetic and 1006 non-diabetic subjects. |
| 2075 | 21814221 | Variants in USF1, ABCC8, ISL1 and KCNJ11 showed nominal association, while haplotypes in these genes were significantly associated. rs3812704 upstream of NEUROG3 significantly increased risk for type 2 diabetes in normal-weight/lean subjects (OR=1.68 (95%CI 1.25-2.24), P=4.9 × 10(-4)). |
| 2076 | 21845205 | Transcription factors, such as hepatocyte nuclear factor-4α and the forkhead box protein-M1, and cell cycle regulators, such as menin, p27 and p18, are important intracellular signals responsible for these effects. |
| 2077 | 21874001 | In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 × 10(-8) to P = 1.9 × 10(-11)). |
| 2078 | 21874001 | SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). |
| 2079 | 21874001 | In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 × 10(-8) to P = 1.9 × 10(-11)). |
| 2080 | 21874001 | SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). |
| 2081 | 22118586 | Giving insights to beta cell function, CHI mutations are now known in eight genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and UCP2). |
| 2082 | 22158537 | The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. |
| 2083 | 22158537 | The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. |
| 2084 | 22158537 | KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. |
| 2085 | 22231386 | The molecular basis of HH involves defects in key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and UCP2) which regulate insulin secretion. |
| 2086 | 22231386 | The most severe forms of HH are due to loss of function mutations in ABCC8/KCNJ11 which encode the SUR1 and KIR6.2 components respectively of the pancreatic β-cell K(ATP) channel. |
| 2087 | 22436693 | Compared with CC, pre- and postnatal LP (RR) decreased β-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Isl1, Rfx6, and Slc2a2 mRNA levels. |
| 2088 | 22436693 | LP only in pregnancy (RC) also decreased β-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Rfx6, and Ins mRNA levels. |
| 2089 | 22436693 | Postnatal LP offspring (CR) showed decreased β-cell mass but increased β-cell fraction, aggregate number, and Hnf1a, Hnf4a, Rfx6, and Slc2a2 mRNA levels. |
| 2090 | 22436693 | Compared with CC, pre- and postnatal LP (RR) decreased β-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Isl1, Rfx6, and Slc2a2 mRNA levels. |
| 2091 | 22436693 | LP only in pregnancy (RC) also decreased β-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Rfx6, and Ins mRNA levels. |
| 2092 | 22436693 | Postnatal LP offspring (CR) showed decreased β-cell mass but increased β-cell fraction, aggregate number, and Hnf1a, Hnf4a, Rfx6, and Slc2a2 mRNA levels. |
| 2093 | 22436693 | Compared with CC, pre- and postnatal LP (RR) decreased β-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Isl1, Rfx6, and Slc2a2 mRNA levels. |
| 2094 | 22436693 | LP only in pregnancy (RC) also decreased β-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Rfx6, and Ins mRNA levels. |
| 2095 | 22436693 | Postnatal LP offspring (CR) showed decreased β-cell mass but increased β-cell fraction, aggregate number, and Hnf1a, Hnf4a, Rfx6, and Slc2a2 mRNA levels. |
| 2096 | 22701567 | Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene. |
| 2097 | 22719926 | We identified an arsenic exposure related 51-gene signature at PND1 and PND70 with several hubs of interaction (Hspa8, IgM and Hnf4a). |
| 2098 | 22719926 | Western blot analysis confirmed changes in the liver at PND70 that included increases of heat shock protein 70 (Hspa8) and active SREBP1. |
| 2099 | 22796301 | Genetic variants in the transcription factor 7-like 2(Tcf7l2) gene have been found to confer a significant risk of type 2 diabetes and attenuated insulin secretion. |
| 2100 | 22796301 | TCF was also found co-localized with peptides that regulate energy homeostasis including AgRP, POMC and NPY. |
| 2101 | 22796301 | TCF7l2, some variants of which have been shown to impair GLP-1-induced insulin secretion, was also found co-localize with GLP-1 in adult TCF wild type progeny. |
| 2102 | 22802087 | Novel presentations of congenital hyperinsulinism due to mutations in the MODY genes: HNF1A and HNF4A. |
| 2103 | 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. |
| 2104 | 22841397 | The mRNA abundance of glucokinase, Cacna1d, acetyl-CoA carboxylase, and insulin also increased. |
| 2105 | 22859960 | The aim of this study was to perform metabolic profiling in urine from patients with MODY due to mutations in the genes encoding glucokinase (GCK) or hepatocyte nuclear factor 1 alpha (HNF1A), type 2 diabetes (T2D) and normoglycaemic control subjects. |
| 2106 | 22902540 | IL1β down-regulation of sex hormone-binding globulin production by decreasing HNF-4α via MEK-1/2 and JNK MAPK pathways. |
| 2107 | 22902540 | We provide evidence that daily IL1β treatment reduces SHBG production in HepG2 cells by the down-regulation of HNF-4A via the MAPK kinase (MEK)-1/2 and c-Jun N-terminal kinase (JNK) MAPK signaling pathways through the activation c-Jun transcription factors. |
| 2108 | 22902540 | The human SHBG promoter sequence contains two putative activator protein 1 (AP1) binding sites recognized by c-Jun transcription factors, but they are not necessary for the IL1β-induced down-regulation of SHBG promoter activity in luciferase reporter gene assays. |
| 2109 | 22902540 | Daily treatment with IL1β reduces hepatic nuclear factor (HNF)-4α mRNA and protein levels via the MEK-1/2 and JNK MAPK signaling pathways. |
| 2110 | 22902540 | Our results show that IL1β reduces hepatic SHBG production by decreasing HNF-4α via MEK-1/2 and JNK MAPK pathways. |
| 2111 | 23071669 | These included five that were common to both ages (TNF, HNF4A, IL15, Progesterone, and YWHAZ), and others that were unique to 2 weeks (e.g. |
| 2112 | 23071669 | MYC/MYCN, TGFB1, and IL2) and to 4 weeks (e.g. |
| 2113 | 23071669 | IFNG, beta-estradiol, p53, NFKB, AKT, PRKCA, IL12, and HLA-C). |
| 2114 | 23071669 | Based on the literature, genes that may play a role in regulating metabolic pathways at 2 weeks include Myc and HNF4A, and at 4 weeks, beta-estradiol, p53, Akt, HNF4A and AR. |
| 2115 | 23071669 | These included five that were common to both ages (TNF, HNF4A, IL15, Progesterone, and YWHAZ), and others that were unique to 2 weeks (e.g. |
| 2116 | 23071669 | MYC/MYCN, TGFB1, and IL2) and to 4 weeks (e.g. |
| 2117 | 23071669 | IFNG, beta-estradiol, p53, NFKB, AKT, PRKCA, IL12, and HLA-C). |
| 2118 | 23071669 | Based on the literature, genes that may play a role in regulating metabolic pathways at 2 weeks include Myc and HNF4A, and at 4 weeks, beta-estradiol, p53, Akt, HNF4A and AR. |
| 2119 | 23139355 | Mutations in the gene encoding glucokinase (GCK) cause a mild hereditary form of diabetes termed maturity-onset diabetes of the young (MODY)2 or GCK-MODY. |
| 2120 | 23139355 | Here, we profiled metabolites in serum from patients with MODY1 (HNF4A), MODY2 (GCK), MODY3 (HNF1A), and type 2 diabetes and from healthy individuals to characterize metabolic perturbations caused by specific mutations. |
| 2121 | 23139355 | Mutations in the gene encoding glucokinase (GCK) cause a mild hereditary form of diabetes termed maturity-onset diabetes of the young (MODY)2 or GCK-MODY. |
| 2122 | 23139355 | Here, we profiled metabolites in serum from patients with MODY1 (HNF4A), MODY2 (GCK), MODY3 (HNF1A), and type 2 diabetes and from healthy individuals to characterize metabolic perturbations caused by specific mutations. |
| 2123 | 23227446 | Mutations in this gene can lead to maturity-onset diabetes of the young (MODY), an uncommon, autosomal dominant, non-insulin dependent form of diabetes. |
| 2124 | 23306198 | Here we report, for the first time, the derivation of human induced pluripotent stem cells (hiPSCs) from patients with five types of MODY: MODY1 (HNF4A), MODY2 (GCK), MODY3 (HNF1A), MODY5 (HNF1B), and MODY8 (CEL) with a polycistronic lentiviral vector expressing a Cre-excisable human "stem cell cassette" containing the four reprogramming factors OCT4, KLF4, SOX2, and CMYC. |
| 2125 | 23306198 | These MODY-hiPSCs morphologically resemble human pluripotent stem cells (hPSCs), express pluripotency markers OCT4, SOX2, NANOG, SSEA-4, and TRA-1-60, give rise to derivatives of the three germ layers in a teratoma assay, and are karyotypically normal. |
| 2126 | 23348805 | Maturity-onset diabetes of the young (MODY) is a monogenic disorder characterized by autosomal dominant inheritance of young-onset (typically <25 years), noninsulin-dependent diabetes due to defective insulin secretion. |
| 2127 | 23348805 | Mutations in the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are the most common cause of MODY in most adult populations studied. |
| 2128 | 23348805 | Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. |
| 2129 | 23348805 | The identification of an HNF1A or HNF4A gene mutation has important implications for clinical management in diabetes and pregnancy, but MODY is significantly underdiagnosed. |
| 2130 | 23348805 | Maturity-onset diabetes of the young (MODY) is a monogenic disorder characterized by autosomal dominant inheritance of young-onset (typically <25 years), noninsulin-dependent diabetes due to defective insulin secretion. |
| 2131 | 23348805 | Mutations in the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are the most common cause of MODY in most adult populations studied. |
| 2132 | 23348805 | Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. |
| 2133 | 23348805 | The identification of an HNF1A or HNF4A gene mutation has important implications for clinical management in diabetes and pregnancy, but MODY is significantly underdiagnosed. |
| 2134 | 23348805 | Maturity-onset diabetes of the young (MODY) is a monogenic disorder characterized by autosomal dominant inheritance of young-onset (typically <25 years), noninsulin-dependent diabetes due to defective insulin secretion. |
| 2135 | 23348805 | Mutations in the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are the most common cause of MODY in most adult populations studied. |
| 2136 | 23348805 | Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. |
| 2137 | 23348805 | The identification of an HNF1A or HNF4A gene mutation has important implications for clinical management in diabetes and pregnancy, but MODY is significantly underdiagnosed. |
| 2138 | 23348805 | Maturity-onset diabetes of the young (MODY) is a monogenic disorder characterized by autosomal dominant inheritance of young-onset (typically <25 years), noninsulin-dependent diabetes due to defective insulin secretion. |
| 2139 | 23348805 | Mutations in the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are the most common cause of MODY in most adult populations studied. |
| 2140 | 23348805 | Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. |
| 2141 | 23348805 | The identification of an HNF1A or HNF4A gene mutation has important implications for clinical management in diabetes and pregnancy, but MODY is significantly underdiagnosed. |
| 2142 | 23433541 | One of the mutations, the deletion 96_98delAAG (p.Lys32del), had not been previously described, reinforcing the worldwide prevalence of GCK MODY and widespread existence of undetected new mutations. |
| 2143 | 23463236 | Persistent effects of an early suboptimal environment, known to increase risk of type 2 diabetes in later life, can alter the epigenetic control of transcriptional master regulators, such as Hnf4a and Pdx1. |
| 2144 | 23551881 | Digenic heterozygous HNF1A and HNF4A mutations in two siblings with childhood-onset diabetes. |
| 2145 | 23551881 | Monogenic diabetes due to mutations in the transcription factor genes hepatocyte nuclear factor 1A (HNF1A) and HNF4A is characterized by islet cell antibody negative, familial diabetes with residual insulin secretion. |
| 2146 | 23551881 | We report two sisters with childhood onset diabetes who are both heterozygous for the most common mutation in each of two transcription factors, HNF1A, and HNF4A. |
| 2147 | 23551881 | Both sisters inherited the HNF4A gene mutation R127W from their mother and the HNF1A gene mutation P291fsinsC (c.872dup) from their father. |
| 2148 | 23551881 | Digenic inheritance of HNF1A and HNF4A mutations is very rare and has only been reported in two families where conclusive evidence for the pathogenicity of their mutations was lacking. |
| 2149 | 23551881 | Follow-up studies in this family co-segregating the two most commonly reported HNF1A/HNF4A mutations will be informative for understanding the effect of digenic inheritance upon phenotypic severity and response to sulfonylurea therapy. |
| 2150 | 23551881 | Digenic heterozygous HNF1A and HNF4A mutations in two siblings with childhood-onset diabetes. |
| 2151 | 23551881 | Monogenic diabetes due to mutations in the transcription factor genes hepatocyte nuclear factor 1A (HNF1A) and HNF4A is characterized by islet cell antibody negative, familial diabetes with residual insulin secretion. |
| 2152 | 23551881 | We report two sisters with childhood onset diabetes who are both heterozygous for the most common mutation in each of two transcription factors, HNF1A, and HNF4A. |
| 2153 | 23551881 | Both sisters inherited the HNF4A gene mutation R127W from their mother and the HNF1A gene mutation P291fsinsC (c.872dup) from their father. |
| 2154 | 23551881 | Digenic inheritance of HNF1A and HNF4A mutations is very rare and has only been reported in two families where conclusive evidence for the pathogenicity of their mutations was lacking. |
| 2155 | 23551881 | Follow-up studies in this family co-segregating the two most commonly reported HNF1A/HNF4A mutations will be informative for understanding the effect of digenic inheritance upon phenotypic severity and response to sulfonylurea therapy. |
| 2156 | 23551881 | Digenic heterozygous HNF1A and HNF4A mutations in two siblings with childhood-onset diabetes. |
| 2157 | 23551881 | Monogenic diabetes due to mutations in the transcription factor genes hepatocyte nuclear factor 1A (HNF1A) and HNF4A is characterized by islet cell antibody negative, familial diabetes with residual insulin secretion. |
| 2158 | 23551881 | We report two sisters with childhood onset diabetes who are both heterozygous for the most common mutation in each of two transcription factors, HNF1A, and HNF4A. |
| 2159 | 23551881 | Both sisters inherited the HNF4A gene mutation R127W from their mother and the HNF1A gene mutation P291fsinsC (c.872dup) from their father. |
| 2160 | 23551881 | Digenic inheritance of HNF1A and HNF4A mutations is very rare and has only been reported in two families where conclusive evidence for the pathogenicity of their mutations was lacking. |
| 2161 | 23551881 | Follow-up studies in this family co-segregating the two most commonly reported HNF1A/HNF4A mutations will be informative for understanding the effect of digenic inheritance upon phenotypic severity and response to sulfonylurea therapy. |
| 2162 | 23551881 | Digenic heterozygous HNF1A and HNF4A mutations in two siblings with childhood-onset diabetes. |
| 2163 | 23551881 | Monogenic diabetes due to mutations in the transcription factor genes hepatocyte nuclear factor 1A (HNF1A) and HNF4A is characterized by islet cell antibody negative, familial diabetes with residual insulin secretion. |
| 2164 | 23551881 | We report two sisters with childhood onset diabetes who are both heterozygous for the most common mutation in each of two transcription factors, HNF1A, and HNF4A. |
| 2165 | 23551881 | Both sisters inherited the HNF4A gene mutation R127W from their mother and the HNF1A gene mutation P291fsinsC (c.872dup) from their father. |
| 2166 | 23551881 | Digenic inheritance of HNF1A and HNF4A mutations is very rare and has only been reported in two families where conclusive evidence for the pathogenicity of their mutations was lacking. |
| 2167 | 23551881 | Follow-up studies in this family co-segregating the two most commonly reported HNF1A/HNF4A mutations will be informative for understanding the effect of digenic inheritance upon phenotypic severity and response to sulfonylurea therapy. |
| 2168 | 23551881 | Digenic heterozygous HNF1A and HNF4A mutations in two siblings with childhood-onset diabetes. |
| 2169 | 23551881 | Monogenic diabetes due to mutations in the transcription factor genes hepatocyte nuclear factor 1A (HNF1A) and HNF4A is characterized by islet cell antibody negative, familial diabetes with residual insulin secretion. |
| 2170 | 23551881 | We report two sisters with childhood onset diabetes who are both heterozygous for the most common mutation in each of two transcription factors, HNF1A, and HNF4A. |
| 2171 | 23551881 | Both sisters inherited the HNF4A gene mutation R127W from their mother and the HNF1A gene mutation P291fsinsC (c.872dup) from their father. |
| 2172 | 23551881 | Digenic inheritance of HNF1A and HNF4A mutations is very rare and has only been reported in two families where conclusive evidence for the pathogenicity of their mutations was lacking. |
| 2173 | 23551881 | Follow-up studies in this family co-segregating the two most commonly reported HNF1A/HNF4A mutations will be informative for understanding the effect of digenic inheritance upon phenotypic severity and response to sulfonylurea therapy. |
| 2174 | 23551881 | Digenic heterozygous HNF1A and HNF4A mutations in two siblings with childhood-onset diabetes. |
| 2175 | 23551881 | Monogenic diabetes due to mutations in the transcription factor genes hepatocyte nuclear factor 1A (HNF1A) and HNF4A is characterized by islet cell antibody negative, familial diabetes with residual insulin secretion. |
| 2176 | 23551881 | We report two sisters with childhood onset diabetes who are both heterozygous for the most common mutation in each of two transcription factors, HNF1A, and HNF4A. |
| 2177 | 23551881 | Both sisters inherited the HNF4A gene mutation R127W from their mother and the HNF1A gene mutation P291fsinsC (c.872dup) from their father. |
| 2178 | 23551881 | Digenic inheritance of HNF1A and HNF4A mutations is very rare and has only been reported in two families where conclusive evidence for the pathogenicity of their mutations was lacking. |
| 2179 | 23551881 | Follow-up studies in this family co-segregating the two most commonly reported HNF1A/HNF4A mutations will be informative for understanding the effect of digenic inheritance upon phenotypic severity and response to sulfonylurea therapy. |
| 2180 | 23616187 | Hepatocyte nuclear factor 1 alpha (HNF1A) mutations cause maturity-onset diabetes of the young (MODY) type 3. |
| 2181 | 23647541 | According to their different action mechanisms or functions, NR superfamily has been classified into seven families: NR1 (thyroid hormone like), NR2 (HNF4-like), NR3 (estrogen like), NR4 (nerve growth factor IB-like), NR5 (fushi tarazu-F1 like), NR6 (germ cell nuclear factor like), and NR0 (knirps or DAX like). |
| 2182 | 23665043 | Hepatocyte nuclear factor 4α regulates the expression of the murine pyruvate carboxylase gene through the HNF4-specific binding motif in its proximal promoter. |
| 2183 | 23761103 | Silencing either of these MODY genes (Hnf1a and Neurod1) mimicked the cellular phenotype caused by miR-24 overexpression, whereas restoring their expression rescued β-cell function. |
| 2184 | 23771925 | Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: results from the SEARCH for Diabetes in Youth. |
| 2185 | 23878349 | Mutations in the GCK and HNF1A/4 A genes account for up to 80% of all MODY cases. |
| 2186 | 23878349 | In contrast, mutations in the genes encoding the transcription factors HNF1A and HNF4A cause a progressive insulin secretory defect and hyperglycaemia that can lead to vascular complications. |
| 2187 | 15615695 | RSK4 and PAK5 are novel candidate genes in diabetic rat kidney and brain. |
| 2188 | 15615695 | In multiple ChIP assays, ribosomal S6 kinase 4 (RSK4) and p21-activated kinase 5 (PAK5) were confirmed, and in vitro binding of HNF4alpha was evidenced by electrophoretic mobility shift assays (EMSA) using oligonucleotides, which harbor novel binding sites. |
| 2189 | 15615695 | We also used EMSA to probe for binding sites in promoters of HNF1alpha, apolipoprotein B, alpha1-antitrypsin, and angiotensinogen. |
| 2190 | 15615695 | We further studied RSK4 and PAK5 kinase expression in streptozotocin-induced diabetic rat kidney and brain and observed significant repression of HNF4alpha, RSK4, and PAK5 as determined by quantitative real-time reverse transcriptase-polymerase chain reaction. |
| 2191 | 15615695 | RSK4 and PAK5 may provide a molecular rationale for late-stage complications in disease, and further studies are warranted to explore these targets for the treatment of diabetic nephro- and neuropathy, frequently seen in patients with HNF4alpha dysfunction. |
| 2192 | 15615695 | RSK4 and PAK5 are novel candidate genes in diabetic rat kidney and brain. |
| 2193 | 15615695 | In multiple ChIP assays, ribosomal S6 kinase 4 (RSK4) and p21-activated kinase 5 (PAK5) were confirmed, and in vitro binding of HNF4alpha was evidenced by electrophoretic mobility shift assays (EMSA) using oligonucleotides, which harbor novel binding sites. |
| 2194 | 15615695 | We also used EMSA to probe for binding sites in promoters of HNF1alpha, apolipoprotein B, alpha1-antitrypsin, and angiotensinogen. |
| 2195 | 15615695 | We further studied RSK4 and PAK5 kinase expression in streptozotocin-induced diabetic rat kidney and brain and observed significant repression of HNF4alpha, RSK4, and PAK5 as determined by quantitative real-time reverse transcriptase-polymerase chain reaction. |
| 2196 | 15615695 | RSK4 and PAK5 may provide a molecular rationale for late-stage complications in disease, and further studies are warranted to explore these targets for the treatment of diabetic nephro- and neuropathy, frequently seen in patients with HNF4alpha dysfunction. |
| 2197 | 15615695 | RSK4 and PAK5 are novel candidate genes in diabetic rat kidney and brain. |
| 2198 | 15615695 | In multiple ChIP assays, ribosomal S6 kinase 4 (RSK4) and p21-activated kinase 5 (PAK5) were confirmed, and in vitro binding of HNF4alpha was evidenced by electrophoretic mobility shift assays (EMSA) using oligonucleotides, which harbor novel binding sites. |
| 2199 | 15615695 | We also used EMSA to probe for binding sites in promoters of HNF1alpha, apolipoprotein B, alpha1-antitrypsin, and angiotensinogen. |
| 2200 | 15615695 | We further studied RSK4 and PAK5 kinase expression in streptozotocin-induced diabetic rat kidney and brain and observed significant repression of HNF4alpha, RSK4, and PAK5 as determined by quantitative real-time reverse transcriptase-polymerase chain reaction. |
| 2201 | 15615695 | RSK4 and PAK5 may provide a molecular rationale for late-stage complications in disease, and further studies are warranted to explore these targets for the treatment of diabetic nephro- and neuropathy, frequently seen in patients with HNF4alpha dysfunction. |