title: Analysis of Foxo1-regulated genes using Foxo1-deficient pancreatic β cells.
abstract: 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 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 β-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 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.
authors: Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
authors: Satsuki
authors: S
authors: Miyazaki
authors: Rie
authors: R
authors: Minamida
authors: Tatsuo
authors: T
authors: Furuyama
authors: Fumi
authors: F
authors: Tashiro
authors: Eiji
authors: E
authors: Yamato
authors: Shinobu
authors: S
authors: Inagaki
authors: Jun-ichi
authors: J
authors: Miyazaki
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000483:Alleles; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation; D002678:Chimera / Q000235:genetics / Q000378:metabolism; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D013539:Simian virus 40 / Q000235:genetics / Q000378:metabolism
chemical_list: D000952:Antigens, Polyomavirus Transforming; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D007328:Insulin; C045073:Cre recombinase; D019426:Integrases; D005947:Glucose