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Analysis of Foxo1 ‐regulated genes using Foxo1‐ deficient pancreatic β cells
Author(s) -
Miyazaki Satsuki,
Minamida Rie,
Furuyama Tatsuo,
Tashiro Fumi,
Yamato Eiji,
Inagaki Shinobu,
Miyazaki Junichi
Publication year - 2012
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2012.01625.x
Subject(s) - foxo1 , biology , cell culture , knockout mouse , conditional gene knockout , transfection , insulinoma , cell , gene expression , microbiology and biotechnology , endocrinology , gene , insulin , phenotype , signal transduction , genetics , protein kinase b
Several reports have suggested that Foxo1 , a key regulator in differentiation, growth and metabolism, is involved in pancreatic β‐cell function. However, detailed analyses have been hampered by a lack of Foxo1 ‐deficient β cells. To elucidate Foxo1's function in β cells, we produced a β‐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 β‐cell line from an insulinoma induced in this knockout mouse by the β‐cell‐specific expression of simian virus 40 T antigen. In this cell line, designated MIN 6‐Foxo1 flox/flox , adenovirus‐mediated Cre expression ablates the Foxo1 gene, generating MIN 6‐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 β‐cell proliferation. We also conducted DNA microarray analyses of MIN 6‐Foxo1‐ KO cells infected with either an adenovirus vector expressing a constitutively active FOXO 1 or a control vector and identified several Foxo1 ‐regulated genes, including some known to be related to β‐cell function. These cells should be useful for further studies on Foxo1 's roles in β‐cells and may lead to novel strategies for treating the impaired insulin secretion in type 2 diabetes mellitus.