| First Author | Khoo C | Year | 2011 |
| Journal | Endocrinology | Volume | 152 |
| Issue | 7 | Pages | 2599-608 |
| PubMed ID | 21540283 | Mgi Jnum | J:174900 |
| Mgi Id | MGI:5141385 | Doi | 10.1210/en.2010-1420 |
| Citation | Khoo C, et al. (2011) Endoplasmic reticulum oxidoreductin-1-like {beta} (ERO1l{beta}) regulates susceptibility to endoplasmic reticulum stress and is induced by insulin flux in {beta}-cells. Endocrinology 152(7):2599-608 |
| abstractText | Hyperglycemia increases insulin flux through the endoplasmic reticulum (ER) of pancreatic beta-cells, and the unfolded protein response pathway is required to enhance insulin processing. Pancreatic and duodenal homeobox 1 (PDX1), a key pancreatic transcription factor, regulates insulin along with targets involved in insulin processing and secretion. Here we find that PDX1 is a direct transcriptional regulator of ER oxidoreductin-1-like beta (Ero1lbeta), which maintains the oxidative environment of the ER to facilitate disulfide bond formation. PDX1 deficiency reduced Ero1lbeta transcript levels in mouse islets and mouse insulinoma (MIN6) cells; moreover, PDX1 occupied the Ero1lbeta promoter in beta-cells. ERO1lbeta levels were induced by high glucose concentrations and by the reducing agent dithiothreitol, indicating potential roles in adaptation to increased oxidative protein folding load in the beta-cell ER. In MIN6 cells, small interfering RNA-mediated silencing of Ero1lbeta decreased insulin content and increased susceptibility to ER stress-induced apoptosis. These findings demonstrate roles for the PDX1 target ERO1lbeta in maintaining insulin content and regulating cell survival during ER stress. |
