| First Author | Ren D | Year | 2014 |
| Journal | Diabetes | Volume | 63 |
| Issue | 8 | Pages | 2744-50 |
| PubMed ID | 24658302 | Mgi Jnum | J:229796 |
| Mgi Id | MGI:5754470 | Doi | 10.2337/db13-1513 |
| Citation | Ren D, et al. (2014) Role of BH3-only molecules Bim and Puma in beta-cell death in Pdx1 deficiency. Diabetes 63(8):2744-50 |
| abstractText | Mutations in pancreatic duodenal homeobox-1 (PDX1) are associated with diabetes in humans. Pdx1-haploinsufficient mice develop diabetes due to an increase in beta-cell death leading to reduced beta-cell mass. For definition of the molecular link between Pdx1 deficiency and beta-cell death, Pdx1-haploinsufficient mice in which the genes for the BH3-only molecules Bim and Puma had been ablated were studied on a high-fat diet. Compared with Pdx1(+/-) mice, animals haploinsufficient for both Pdx1 and Bim or Puma genes showed improved glucose tolerance, enhanced beta-cell mass, and reduction in the number of TUNEL-positive cells in islets. These results suggest that Bim and Puma ablation improves beta-cell survival in Pdx1(+/-) mice. For exploration of the mechanisms responsible for these findings, Pdx1 gene expression was knocked down in mouse MIN6 insulinoma cells resulting in apoptotic cell death that was found to be associated with increased expression of BH3-only molecules Bim and Puma. If the upregulation of Bim and Puma that occurs during Pdx1 suppression was prevented, apoptotic beta-cell death was reduced in vitro. These results suggest that Bim and Puma play an important role in beta-cell apoptosis in Pdx1-deficient diabetes. |
