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

gene/protein

HIF1A

interacts (colocalizes) with

gene/protein

ARNT

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

gene/protein

HIF1A

affects_activity of

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

gene/protein

HIF1A

affects_activity of

phenotype

reduced pancreatic beta cell function

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

gene/protein

HIF1A

affects_expression of

gene/protein

SLC2A2

in pancreas, in pancreatic beta cells
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

gene/protein

HIF1A

affects_expression of

gene/protein

GCK

in pancreas, in pancreatic beta cells
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

gene/protein

HIF1A

affects_expression of

gene/protein

GPI

in pancreas, in pancreatic beta cells
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

gene/protein

HIF1A

affects_expression of

gene/protein

PFK

in pancreas, in pancreatic beta cells
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

gene/protein

HIF1A

affects_expression of

gene/protein

HNF4A

in pancreas, in pancreatic beta cells
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

gene/protein

HIF1A

affects_expression of

gene/protein

PGAM2

in pancreas, in pancreatic beta cells
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

gene/protein

HIF1A

affects_expression of

gene/protein

AKT2

in pancreas, in pancreatic beta cells
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

HIF1A

affects_activity of

phenotype

decreased intracellular ATP level

in pancreas, in pancreatic beta cells
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

gene/protein

HIF1A

increases_expression of

gene/protein

ARNT

in pancreas, in pancreatic beta cells
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

HIF1A

in pancreas, in pancreatic beta cells
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

in pancreas, in pancreatic beta cells
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

drug/chemical compound

Iron

decreases_expression of

gene/protein

HIF1A

in pancreas, in pancreatic beta cells
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

drug/chemical compound

Iron

decreases_expression of

gene/protein

HNF4A

in pancreas, in pancreatic beta cells
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

drug/chemical compound

Iron

decreases_expression of

gene/protein

SLC2A1

in pancreas, in pancreatic beta cells
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

drug/chemical compound

Iron

decreases_expression of

gene/protein

SLC2A2

in pancreas, in pancreatic beta cells
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

Iron

decreases_activity of

in pancreas, in pancreatic beta cells
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

in pancreas, in pancreatic beta cells
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

in pancreas, in pancreatic beta cells