Analysis of Foxo1-regulated genes using Foxo1-deficient pancreatic ß cells.
Genes Cells
; 17(9): 758-67, 2012 Sep.
Article
em En
| MEDLINE
| ID: mdl-22845550
ABSTRACT
Several reports have suggested that Foxo1, a key regulator in differentiation, growth and metabolism, is involved in pancreatic ß-cell function. However, detailed analyses have been hampered by a lack of Foxo1-deficient ß cells. To elucidate Foxo1's function in ß cells, we produced a ß-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 ß-cell line from an insulinoma induced in this knockout mouse by the ß-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 ß-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 ß-cell function. These cells should be useful for further studies on Foxo1's roles in ß-cells and may lead to novel strategies for treating the impaired insulin secretion in type 2 diabetes mellitus.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
/
Células Secretoras de Insulina
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Fatores de Transcrição Forkhead
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Insulina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article