General Information:
Id: | 4,140 |
Diseases: |
Diabetes mellitus, type II
- [OMIM]
Insulin resistance |
Mus musculus | |
article | |
Reference: | Cheng K et al.(2010) Hypoxia-inducible factor-1alpha regulates beta cell function in mouse and human islets J. Clin. Invest. 120: 2171-2183 [PMID: 20440072] |
Interaction Information:
Comment | To confirm that ARNT was bound to HIF-1alpha, coimmunoprecipitation studies were performed in Min6 cells. Immunoprecipitation with ARNT antibodies revealed low levels of associated HIF-1alpha in the cytoplasm and nucleus, under normoxic conditions. |
Formal Description Interaction-ID: 42685 |
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Drugbank entries | Show/Hide entries for HIF1A |
Comment | C57BL/6 mice with beta cell-specific Hif1a disruption (beta-Hif1a-null mice) exhibited glucose intolerance, beta cell dysfunction, and developed severe glucose intolerance on a high-fat diet. |
Formal Description Interaction-ID: 42689 |
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Drugbank entries | Show/Hide entries for HIF1A |
Comment | C57BL/6 mice with beta cell-specific Hif1a disruption (beta-Hif1a-null mice) exhibited glucose intolerance, beta cell dysfunction, and developed severe glucose intolerance on a high-fat diet. |
Formal Description Interaction-ID: 42690 |
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Drugbank entries | Show/Hide entries for HIF1A |
Comment | In beta-Hif1a-null islets, there was a more than 40% decrease in Glut2, glucokinase (Gck), glucose-6-phosphoisomerase (G6pi), phosphofructokinase (Pfk), hepatocyte nuclear factor 4alpha (Hnf4a), phosphoglycerate mutase 2 (Pgam2), and Akt2. |
Formal Description Interaction-ID: 42691 |
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Drugbank entries | Show/Hide entries for HIF1A or SLC2A2 |
Comment | In beta-Hif1a-null islets, there was a more than 40% decrease in Glut2, glucokinase (Gck), glucose-6-phosphoisomerase (G6pi), phosphofructokinase (Pfk), hepatocyte nuclear factor 4alpha (Hnf4a), phosphoglycerate mutase 2 (Pgam2), and Akt2. |
Formal Description Interaction-ID: 42692 |
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Drugbank entries | Show/Hide entries for HIF1A or GCK |
Comment | In beta-Hif1a-null islets, there was a more than 40% decrease in Glut2, glucokinase (Gck), glucose-6-phosphoisomerase (G6pi), phosphofructokinase (Pfk), hepatocyte nuclear factor 4alpha (Hnf4a), phosphoglycerate mutase 2 (Pgam2), and Akt2. |
Formal Description Interaction-ID: 42693 |
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Drugbank entries | Show/Hide entries for HIF1A or GPI |
Comment | In beta-Hif1a-null islets, there was a more than 40% decrease in Glut2, glucokinase (Gck), glucose-6-phosphoisomerase (G6pi), phosphofructokinase (Pfk), hepatocyte nuclear factor 4alpha (Hnf4a), phosphoglycerate mutase 2 (Pgam2), and Akt2. |
Formal Description Interaction-ID: 42694 |
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Drugbank entries | Show/Hide entries for HIF1A |
Comment | In beta-Hif1a-null islets, there was a more than 40% decrease in Glut2, glucokinase (Gck), glucose-6-phosphoisomerase (G6pi), phosphofructokinase (Pfk), hepatocyte nuclear factor 4alpha (Hnf4a), phosphoglycerate mutase 2 (Pgam2), and Akt2. |
Formal Description Interaction-ID: 42695 |
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Drugbank entries | Show/Hide entries for HIF1A or HNF4A |
Comment | In beta-Hif1a-null islets, there was a more than 40% decrease in Glut2, glucokinase (Gck), glucose-6-phosphoisomerase (G6pi), phosphofructokinase (Pfk), hepatocyte nuclear factor 4alpha (Hnf4a), phosphoglycerate mutase 2 (Pgam2), and Akt2. |
Formal Description Interaction-ID: 42696 |
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Drugbank entries | Show/Hide entries for HIF1A or PGAM2 |
Comment | In beta-Hif1a-null islets, there was a more than 40% decrease in Glut2, glucokinase (Gck), glucose-6-phosphoisomerase (G6pi), phosphofructokinase (Pfk), hepatocyte nuclear factor 4alpha (Hnf4a), phosphoglycerate mutase 2 (Pgam2), and Akt2. |
Formal Description Interaction-ID: 42697 |
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Drugbank entries | Show/Hide entries for HIF1A or AKT2 |
Comment | Control islets had higher ATP content after exposure to high glucose. Islets from beta-Hif1a-null mice had significantly lower basal ATP levels (60% decrease) and the increase in ATP levels with 25 mmol/l glucose was severely blunted. This was despite similar islet insulin content and nonsignificant, higher beta cell content in beta-Hif1a-null mice. |
Formal Description Interaction-ID: 42698 |
gene/protein affects_activity of phenotype decreased intracellular ATP level |
Drugbank entries | Show/Hide entries for HIF1A |
Comment | RNAi-mediated knockdown of Hif1a in Min6 cells caused a more than 80% decrease in Arnt expression, and islets from beta-Hif1a-null mice had a 50% decrease in Arnt expression, which was similar to the reduction in Hif1a itself. This was paralleled by a decrease in ARNT protein in immunostained pancreas of beta-Hif1a-null versus floxed control mice. Together these experiments show that decreasing HIF-1alpha in islets and beta cells led to decreased ARNT. |
Formal Description Interaction-ID: 42708 |
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Drugbank entries | Show/Hide entries for HIF1A |
Comment | Removing iron by chelation improved HIF-1alpha activity and beta cell function. |
Formal Description Interaction-ID: 42717 |
drug/chemical compound Iron chelator increases_activity of gene/protein |
Drugbank entries | Show/Hide entries for HIF1A |
Comment | Removing iron by chelation improved HIF-1alpha activity and beta cell function. |
Formal Description Interaction-ID: 42723 |
drug/chemical compound Iron chelator decreases_activity of phenotype reduced pancreatic beta cell function |
Comment | The effect of adding iron in the form of ferric citrate was studied. At high doses, there was obvious cell death. At lower doses, there were significant decreases in Hif1a, Hnf4a, Glut1, and Glut2 expression. There was also significantly impaired glucose-stimulated insulin secretion (GSIS), with only a nonsignificant 13% increase, following high glucose in iron-treated cells. |
Formal Description Interaction-ID: 42724 |
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Drugbank entries | Show/Hide entries for HIF1A |
Comment | The effect of adding iron in the form of ferric citrate was studied. At high doses, there was obvious cell death. At lower doses, there were significant decreases in Hif1a, Hnf4a, Glut1, and Glut2 expression. There was also significantly impaired glucose-stimulated insulin secretion (GSIS), with only a nonsignificant 13% increase, following high glucose in iron-treated cells. |
Formal Description Interaction-ID: 42725 |
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Drugbank entries | Show/Hide entries for HNF4A |
Comment | The effect of adding iron in the form of ferric citrate was studied. At high doses, there was obvious cell death. At lower doses, there were significant decreases in Hif1a, Hnf4a, Glut1, and Glut2 expression. There was also significantly impaired glucose-stimulated insulin secretion (GSIS), with only a nonsignificant 13% increase, following high glucose in iron-treated cells. |
Formal Description Interaction-ID: 42726 |
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Comment | The effect of adding iron in the form of ferric citrate was studied. At high doses, there was obvious cell death. At lower doses, there were significant decreases in Hif1a, Hnf4a, Glut1, and Glut2 expression. There was also significantly impaired glucose-stimulated insulin secretion (GSIS), with only a nonsignificant 13% increase, following high glucose in iron-treated cells. |
Formal Description Interaction-ID: 42727 |
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Drugbank entries | Show/Hide entries for SLC2A2 |
Comment | The effect of adding iron in the form of ferric citrate was studied. At high doses, there was obvious cell death. At lower doses, there were significant decreases in Hif1a, Hnf4a, Glut1, and Glut2 expression. There was also significantly impaired glucose-stimulated insulin secretion (GSIS), with only a nonsignificant 13% increase, following high glucose in iron-treated cells. |
Formal Description Interaction-ID: 42728 |
drug/chemical compound decreases_activity of |
Comment | Increasing HIF-1alpha levels by inhibiting its degradation through iron chelation markedly improved insulin secretion and glucose tolerance in control mice fed a high-fat diet but not in beta-Hif1a-null mice. |
Formal Description Interaction-ID: 42729 |
drug/chemical compound Iron chelator increases_activity of |
Comment | Increasing HIF-1alpha levels by inhibiting its degradation through iron chelation markedly improved insulin secretion and glucose tolerance in control mice fed a high-fat diet but not in beta-Hif1a-null mice. |
Formal Description Interaction-ID: 42730 |
drug/chemical compound Iron chelator increases_activity of phenotype |