| First Author | Miyazaki S | Year | 2012 |
| Journal | Genes Cells | Volume | 17 |
| Issue | 9 | Pages | 758-67 |
| PubMed ID | 22845550 | Mgi Jnum | J:195101 |
| Mgi Id | MGI:5476421 | Doi | 10.1111/j.1365-2443.2012.01625.x |
| Citation | Miyazaki S, et al. (2012) Analysis of Foxo1-regulated genes using Foxo1-deficient pancreatic beta cells. Genes Cells 17(9):758-67 |
| abstractText | Several reports have suggested that Foxo1, a key regulator in differentiation, growth and metabolism, is involved in pancreatic beta-cell function. However, detailed analyses have been hampered by a lack of Foxo1-deficient beta cells. To elucidate Foxo1's function in beta cells, we produced a beta-cell line with inducible Foxo1 deletion. We generated a conditional knockout mouse line, in which Cre recombinase deletes the Foxo1 gene. We then established a beta-cell line from an insulinoma induced in this knockout mouse by the beta-cell-specific expression of simian virus 40 T antigen. In this cell line, designated MIN6-Foxo1flox/flox, adenovirus-mediated Cre expression ablates the Foxo1 gene, generating MIN6-Foxo1-KO cells. Using these knockout and floxed cell lines, we found that Foxo1 ablation enhanced the glucose-stimulated insulin secretion (GSIS) at high glucose concentrations and enhanced beta-cell proliferation. We also conducted DNA microarray analyses of MIN6-Foxo1-KO cells infected with either an adenovirus vector expressing a constitutively active FOXO1 or a control vector and identified several Foxo1-regulated genes, including some known to be related to beta-cell function. These cells should be useful for further studies on Foxo1's roles in beta-cells and may lead to novel strategies for treating the impaired insulin secretion in type 2 diabetes mellitus. |
