General Information:

Id: 6,130
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Mus musculus
BTO:0002284 MIN-6 cell
article
Reference: Sato Y et al.(2014) Moderate hypoxia induces beta-cell dysfunction with HIF-1-independent gene expression changes PLoS ONE 9 [PMID: 25503986]

Interaction Information:

Comment It has been demonstrated that beta-cells become hypoxic under high glucose conditions due to increased oxygen consumption and that the pancreatic islets of diabetic mice but not those of control mice are moderately hypoxic. In the present study, moderate hypoxia induced a hypoxic response in MIN6 cells, as evidenced by increased levels of HIF-1alpha protein and target genes. Under these conditions, a selective downregulation of Mafa, Pdx1, Slc2a2, Ndufa5, Kcnj11, Ins1, Wfs1, Foxa2, and Neurod1, which play important roles in beta-cells, was also observed in both MIN6 cells and isolated pancreatic islets.
Formal Description
Interaction-ID: 57351

increases_expression of

gene/protein

HIF1A

Drugbank entries Show/Hide entries for HIF1A
Comment It has been demonstrated that beta-cells become hypoxic under high glucose conditions due to increased oxygen consumption and that the pancreatic islets of diabetic mice but not those of control mice are moderately hypoxic. In the present study, moderate hypoxia induced a hypoxic response in MIN6 cells, as evidenced by increased levels of HIF-1alpha protein and target genes. Under these conditions, a selective downregulation of Mafa, Pdx1, Slc2a2, Ndufa5, Kcnj11, Ins1, Wfs1, Foxa2, and Neurod1, which play important roles in beta-cells, was also observed in both MIN6 cells and isolated pancreatic islets.
Formal Description
Interaction-ID: 57416

decreases_expression of

gene/protein

MAFA

Comment It has been demonstrated that beta-cells become hypoxic under high glucose conditions due to increased oxygen consumption and that the pancreatic islets of diabetic mice but not those of control mice are moderately hypoxic. In the present study, moderate hypoxia induced a hypoxic response in MIN6 cells, as evidenced by increased levels of HIF-1alpha protein and target genes. Under these conditions, a selective downregulation of Mafa, Pdx1, Slc2a2, Ndufa5, Kcnj11, Ins1, Wfs1, Foxa2, and Neurod1, which play important roles in beta-cells, was also observed in both MIN6 cells and isolated pancreatic islets.
Formal Description
Interaction-ID: 57417

decreases_expression of

gene/protein

PDX1

Comment It has been demonstrated that beta-cells become hypoxic under high glucose conditions due to increased oxygen consumption and that the pancreatic islets of diabetic mice but not those of control mice are moderately hypoxic. In the present study, moderate hypoxia induced a hypoxic response in MIN6 cells, as evidenced by increased levels of HIF-1alpha protein and target genes. Under these conditions, a selective downregulation of Mafa, Pdx1, Slc2a2, Ndufa5, Kcnj11, Ins1, Wfs1, Foxa2, and Neurod1, which play important roles in beta-cells, was also observed in both MIN6 cells and isolated pancreatic islets.
Formal Description
Interaction-ID: 57418

decreases_expression of

gene/protein

SLC2A2

Drugbank entries Show/Hide entries for SLC2A2
Comment It has been demonstrated that beta-cells become hypoxic under high glucose conditions due to increased oxygen consumption and that the pancreatic islets of diabetic mice but not those of control mice are moderately hypoxic. In the present study, moderate hypoxia induced a hypoxic response in MIN6 cells, as evidenced by increased levels of HIF-1alpha protein and target genes. Under these conditions, a selective downregulation of Mafa, Pdx1, Slc2a2, Ndufa5, Kcnj11, Ins1, Wfs1, Foxa2, and Neurod1, which play important roles in beta-cells, was also observed in both MIN6 cells and isolated pancreatic islets.
Formal Description
Interaction-ID: 57419

decreases_expression of

gene/protein

NDUFA5

Drugbank entries Show/Hide entries for NDUFA5
Comment It has been demonstrated that beta-cells become hypoxic under high glucose conditions due to increased oxygen consumption and that the pancreatic islets of diabetic mice but not those of control mice are moderately hypoxic. In the present study, moderate hypoxia induced a hypoxic response in MIN6 cells, as evidenced by increased levels of HIF-1alpha protein and target genes. Under these conditions, a selective downregulation of Mafa, Pdx1, Slc2a2, Ndufa5, Kcnj11, Ins1, Wfs1, Foxa2, and Neurod1, which play important roles in beta-cells, was also observed in both MIN6 cells and isolated pancreatic islets.
Formal Description
Interaction-ID: 57420

decreases_expression of

gene/protein

KCNJ11

Drugbank entries Show/Hide entries for KCNJ11
Comment It has been demonstrated that beta-cells become hypoxic under high glucose conditions due to increased oxygen consumption and that the pancreatic islets of diabetic mice but not those of control mice are moderately hypoxic. In the present study, moderate hypoxia induced a hypoxic response in MIN6 cells, as evidenced by increased levels of HIF-1alpha protein and target genes. Under these conditions, a selective downregulation of Mafa, Pdx1, Slc2a2, Ndufa5, Kcnj11, Ins1, Wfs1, Foxa2, and Neurod1, which play important roles in beta-cells, was also observed in both MIN6 cells and isolated pancreatic islets.
Formal Description
Interaction-ID: 57421

decreases_expression of

gene/protein

INS

Drugbank entries Show/Hide entries for INS
Comment It has been demonstrated that beta-cells become hypoxic under high glucose conditions due to increased oxygen consumption and that the pancreatic islets of diabetic mice but not those of control mice are moderately hypoxic. In the present study, moderate hypoxia induced a hypoxic response in MIN6 cells, as evidenced by increased levels of HIF-1alpha protein and target genes. Under these conditions, a selective downregulation of Mafa, Pdx1, Slc2a2, Ndufa5, Kcnj11, Ins1, Wfs1, Foxa2, and Neurod1, which play important roles in beta-cells, was also observed in both MIN6 cells and isolated pancreatic islets.
Formal Description
Interaction-ID: 57422

decreases_expression of

gene/protein

WFS1

Comment It has been demonstrated that beta-cells become hypoxic under high glucose conditions due to increased oxygen consumption and that the pancreatic islets of diabetic mice but not those of control mice are moderately hypoxic. In the present study, moderate hypoxia induced a hypoxic response in MIN6 cells, as evidenced by increased levels of HIF-1alpha protein and target genes. Under these conditions, a selective downregulation of Mafa, Pdx1, Slc2a2, Ndufa5, Kcnj11, Ins1, Wfs1, Foxa2, and Neurod1, which play important roles in beta-cells, was also observed in both MIN6 cells and isolated pancreatic islets.
Formal Description
Interaction-ID: 57423

decreases_expression of

gene/protein

FOXA2

Comment It has been demonstrated that beta-cells become hypoxic under high glucose conditions due to increased oxygen consumption and that the pancreatic islets of diabetic mice but not those of control mice are moderately hypoxic. In the present study, moderate hypoxia induced a hypoxic response in MIN6 cells, as evidenced by increased levels of HIF-1alpha protein and target genes. Under these conditions, a selective downregulation of Mafa, Pdx1, Slc2a2, Ndufa5, Kcnj11, Ins1, Wfs1, Foxa2, and Neurod1, which play important roles in beta-cells, was also observed in both MIN6 cells and isolated pancreatic islets.
Formal Description
Interaction-ID: 57424

decreases_expression of

gene/protein

NEUROD1

Comment Consistent with the altered expression of these genes, abnormal insulin secretion was detected in hypoxic MIN6 cells.
Formal Description
Interaction-ID: 57425

affects_activity of

Comment Moderate hypoxia induced apoptosis in MIN6 cells.
Formal Description
Interaction-ID: 57426

increases_activity of

Comment HIF-1 activates the transcription of genes encoding glucose transporters, glycolytic enzymes, Pdk1 (encoding pyruvate dehydrogenase kinase), and Ldha (encoding lactate dehydrogenase). Expression of the HIF-1 target genes was significantly increased in the hypoxic MIN6 cells. Consistent with the changes in the gene expression of Pdk1 and Ldha, MIN6 cells under hypoxic conditions secreted more lactate.
Formal Description
Interaction-ID: 57427

increases_expression of

gene/protein

PDK1

via HIF1A
Drugbank entries Show/Hide entries for PDK1
Comment HIF-1 activates the transcription of genes encoding glucose transporters, glycolytic enzymes, Pdk1 (encoding pyruvate dehydrogenase kinase), and Ldha (encoding lactate dehydrogenase). Expression of the HIF-1 target genes was significantly increased in the hypoxic MIN6 cells. Consistent with the changes in the gene expression of Pdk1 and Ldha, MIN6 cells under hypoxic conditions secreted more lactate.
Formal Description
Interaction-ID: 57428

increases_expression of

gene/protein

LDHA

via HIF1A
Drugbank entries Show/Hide entries for LDHA
Comment Expression of Hnf1a, Nkx2.2, and Hnf4a mRNA was also significantly decreased in hypoxic MIN6 cells.
Formal Description
Interaction-ID: 57429

decreases_expression of

gene/protein

HNF1A

Drugbank entries Show/Hide entries for HNF1A
Comment Expression of Hnf1a, Nkx2.2, and Hnf4a mRNA was also significantly decreased in hypoxic MIN6 cells.
Formal Description
Interaction-ID: 57430

decreases_expression of

gene/protein

NKX2-2

Comment Expression of Hnf1a, Nkx2.2, and Hnf4a mRNA was also significantly decreased in hypoxic MIN6 cells.
Formal Description
Interaction-ID: 57431

decreases_expression of

gene/protein

HNF4A

Drugbank entries Show/Hide entries for HNF4A
Comment There was a significant reduction in Slc2a2 (encoding GLUT2), Kcnj11 (encoding Kir6.2), Ins1, Wfs1, Glp1r, Irs1, and Abcc8 (encoding SUR1) mRNA expression in MIN6 cells under hypoxia.
Formal Description
Interaction-ID: 57432

decreases_expression of

gene/protein

GLP1R

Drugbank entries Show/Hide entries for GLP1R
Comment There was a significant reduction in Slc2a2 (encoding GLUT2), Kcnj11 (encoding Kir6.2), Ins1, Wfs1, Glp1r, Irs1, and Abcc8 (encoding SUR1) mRNA expression in MIN6 cells under hypoxia.
Formal Description
Interaction-ID: 57433

decreases_expression of

gene/protein

ABCC8

Drugbank entries Show/Hide entries for ABCC8
Comment There was a significant reduction in Slc2a2 (encoding GLUT2), Kcnj11 (encoding Kir6.2), Ins1, Wfs1, Glp1r, Irs1, and Abcc8 (encoding SUR1) mRNA expression in MIN6 cells under hypoxia.
Formal Description
Interaction-ID: 57434

decreases_expression of

gene/protein

IRS1

Drugbank entries Show/Hide entries for IRS1
Comment Islet amyloid polypeptide (IAPP) aggregates into oligomers and forms fibrils in the islets, and the amyloid deposits are associated with reduced beta-cell mass in type 2 diabetic patients. An increased Iapp mRNA level was detected in the hypoxic MIN6 cells.
Formal Description
Interaction-ID: 57435

increases_expression of

gene/protein

IAPP

Comment Regarding the receptors, Glp1r mRNA was significantly decreased, whereas expression of Igf1r, Insr, and Gipr mRNA was significantly increased under hypoxic conditions.
Formal Description
Interaction-ID: 57436

increases_expression of

gene/protein

IGF1R

Drugbank entries Show/Hide entries for IGF1R
Comment Regarding the receptors, Glp1r mRNA was significantly decreased, whereas expression of Igf1r, Insr, and Gipr mRNA was significantly increased under hypoxic conditions.
Formal Description
Interaction-ID: 57437

increases_expression of

gene/protein

INSR

Drugbank entries Show/Hide entries for INSR
Comment Regarding the receptors, Glp1r mRNA was significantly decreased, whereas expression of Igf1r, Insr, and Gipr mRNA was significantly increased under hypoxic conditions.
Formal Description
Interaction-ID: 57438

increases_expression of

gene/protein

GIPR