| First Author | Sato Y | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 12 | Pages | e114868 |
| PubMed ID | 25503986 | Mgi Jnum | J:225196 |
| Mgi Id | MGI:5691847 | Doi | 10.1371/journal.pone.0114868 |
| Citation | Sato Y, et al. (2014) Moderate hypoxia induces beta-cell dysfunction with HIF-1-independent gene expression changes. PLoS One 9(12):e114868 |
| abstractText | Pancreatic beta-cell failure is central to the development and progression of type 2 diabetes. We recently 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. However, the impact of moderate hypoxia on beta-cell number and function is unknown. 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. Consistent with the altered expression of these genes, abnormal insulin secretion was detected in hypoxic MIN6 cells. Most of the hypoxia-induced gene downregulation in MIN6 cells was not affected by the suppression of HIF-1alpha, suggesting a HIF-1-independent mechanism. Moderate hypoxia also induced apoptosis in MIN6 cells. These results suggest that hypoxia is a novel stressor of beta-cells and that hypoxic stress may play a role in the deterioration of beta-cell function. |
