| First Author | Yamamoto Y | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 483 |
| Issue | 1 | Pages | 418-424 |
| PubMed ID | 28017717 | Mgi Jnum | J:241963 |
| Mgi Id | MGI:5904094 | Doi | 10.1016/j.bbrc.2016.12.128 |
| Citation | Yamamoto Y, et al. (2017) Preserving expression of Pdx1 improves beta-cell failure in diabetic mice. Biochem Biophys Res Commun 483(1):418-424 |
| abstractText | Pdx1, a beta-cell-specific transcription factor, has been shown to play a crucial role in maintaining beta-cell function through transactivation of beta-cell-related genes. In addition, it has been reported that the expression levels of Pdx1 are compromised under diabetic conditions in human and rodent models. We therefore aimed to clarify the possible beneficial role of Pdx1 against beta-cell failure and generated the transgenic mouse that expressed Pdx1 conditionally and specifically in beta cells (betaPdx1) and crossed these mice with Ins2Akita diabetic mice. Whereas Pdx1 mRNA levels were reduced in Ins2Akita mice compared with their non-diabetic littermates, the mRNA levels of Pdx1 were significantly recovered in the islets of betaPdx1; Ins2Akita mice. The betaPdx1; Ins2Akita mice exhibited significantly improved glucose tolerance, compared with control Ins2Akita littermates, accompanied by increased insulin secretion after glucose loading. Furthermore, histological examination demonstrated that betaPdx1; Ins2Akita mice had improved localization of SLC2A2 (GLUT2), and quantitative RT-PCR showed the recovered expression of Mafa and Gck mRNAs in the islets of betaPdx1; Ins2Akita mice. These findings suggest that the sustained expression of Pdx1 improves beta-cell failure in Ins2Akita mice, at least partially through the preserving expression of beta-cell-specific genes as well as improved localization of GLUT2. |
