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

作者：Jee Seungwan; Hwang Daeyoun^*; Seo Sujin; Kim Yongkyu; Kim Chuelkyu; Kim Byungguk; Shim Sunbo; Lee Suhae; Sin Jisoon; Bae Changjun; Lee Byoungchun; Jang Meekyung; Kim Minsun; Yim Suyoun; Jang Insurk; Cho Jungsik; Chae Kabryong

来源：International Journal of Molecular Medicine, 2007, 20(6): 829-835.

• microarray
• siRNA
• IDE
• insulin
• diabetes model

To characterize the changes in global gene expression in the livers of H1/siRNA(insulin)-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/siRNA(insulin)-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.

• 出版日期2007-12