101. Transcriptional Profiling of Diabetic Neuropathy in the BKS db/db Mouse.
- Author
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Pande, Manjusha, Hur, Junguk, Yu Hong, Backus, Carey, Hayes, John M., Sang Su Oh, Kretzler, Matthias, and Feldman, Eva L.
- Subjects
DIABETES ,DIABETIC neuropathies ,GENE expression ,LIPID metabolism ,GENES - Abstract
OBJECTIVE -- A better understanding of the molecular mechanisms underlying the development and progression of diabetic neuropathy (DN) is essential for the design of mechanism-based therapies. We examined changes in global gene expression to define pathways regulated by diabetes in peripheral nerve. RESEARCH DESIGN AND METHODS -- Microarray data for 24-week-old BKS db/db and db/+ mouse sciatic nerve were analyzed to define significantly differentially expressed genes (DEGs); DEGs were further analyzed to identify regulated biological processes and pathways. Expression profile clustering was performed to identify coexpressed DEGs. A set of coexpressed lipid metabolism genes was used for promoter sequence analysis. RESULTS -- Gene expression changes are consistent with structural changes of axonal degeneration. Pathways regulated in the db/db nerve include lipid metabolism, carbohydrate metabolism, energy metabolism, peroxisome proliferator-activated receptor signaling, apoptosis, and axon guidance. Promoter sequences of lipid metabolism-related genes exhibit evidence of coregulation of lipid metabolism and nervous system development genes. CONCLUSIONS -- Our data support existing hypotheses regarding hyperglycemia-mediated nerve damage in DN. Moreover, our analyses revealed a possible coregulation mechanism connecting hyperlipidemia and axonal degeneration. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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