title: Microarray analysis of insulin-regulated gene expression in the liver: the use of transgenic mice co-expressing insulin-siRNA and human IDE as an animal model.
abstract: To characterize the changes in global gene expression in the livers of H1/siRNAinsulin-CMV/hIDE transgenic (Tg) mice in response to the reduced bioavailability of insulin, total RNA extracted from the livers of 20-week-old Tg and non-Tg mice was converted to cDNA, labeled with biotin and hybridized to oligonucleotide microarrays. The microarray results were confirmed by a real-time reverse transcription-polymerase chain reaction. Two hundred and fifty-one and 73 genes were up- and down-regulated, respectively by insulin in H1/siRNAinsulin-CMV/hIDE Tg mice compared to the controls. Genes encoding for physiological processes, extracellular defense response and response to biotic stimuli were significantly over-represented in the up-regulated group. Among the down-regulated transcripts, those encoding for extracellular matrix proteins were dramatically over-represented, followed by those related to monooxygenase and oxidoreductase activities. The major genes in the up-regulated categories included Egr1, Saa2, Atf3, DNAJB1 and cCL2, whereas those in the down-regulated categories were Cyp17a1, Adn, Gadd45g, Eno3 and Moxd1. These results indicate that the microarray analysis identifies several gene functional groups and individual genes that respond to a sustained reduction in the insulin levels in the livers of Tg mice. These results also suggest that microarray testing is a useful tool for the better understanding of insulin-regulated diabetes-related diseases.
authors.affiliation: Laboratory Animal Resources Team, National Institute of Toxicological Research, Korea FDA, Seoul 122-704, Korea.
authors.forename: Seungwan
authors.initials: S
authors.lastname: Jee
authors.forename: Daeyoun
authors.initials: D
authors.lastname: Hwang
authors.forename: Sujin
authors.initials: S
authors.lastname: Seo
authors.forename: Yongkyu
authors.initials: Y
authors.lastname: Kim
authors.forename: Chuelkyu
authors.initials: C
authors.lastname: Kim
authors.forename: Byungguk
authors.initials: B
authors.lastname: Kim
authors.forename: Sunbo
authors.initials: S
authors.lastname: Shim
authors.forename: Suhae
authors.initials: S
authors.lastname: Lee
authors.forename: Jisoon
authors.initials: J
authors.lastname: Sin
authors.forename: Changjun
authors.initials: C
authors.lastname: Bae
authors.forename: Byoungchun
authors.initials: B
authors.lastname: Lee
authors.forename: Meekyung
authors.initials: M
authors.lastname: Jang
authors.forename: Minsun
authors.initials: M
authors.lastname: Kim
authors.forename: Suyoun
authors.initials: S
authors.lastname: Yim
authors.forename: Insurk
authors.initials: I
authors.lastname: Jang
authors.forename: Jungsik
authors.initials: J
authors.lastname: Cho
authors.forename: Kabryong
authors.initials: K
authors.lastname: Chae
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D007339:Insulysin / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D034741:RNA, Small Interfering; D007339:Insulysin