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Publication : Transcriptional profiling of diabetic neuropathy in the BKS db/db mouse: a model of type 2 diabetes.

First Author  Pande M Year  2011
Journal  Diabetes Volume  60
Issue  7 Pages  1981-9
PubMed ID  21617178 Mgi Jnum  J:186750
Mgi Id  MGI:5433004 Doi  10.2337/db10-1541
Citation  Pande M, et al. (2011) Transcriptional profiling of diabetic neuropathy in the BKS db/db mouse: a model of type 2 diabetes. Diabetes 60(7):1981-9
abstractText  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.
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