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

Manjusha Pande, Junguk Hur, Yu Hong, Carey Backus, John M. Hayes, Sang Su Oh, Matthias Kretzler, Eva L. Feldman

Research output: Contribution to journalArticle

59 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1981-1989
Number of pages9
JournalDiabetes
Volume60
Issue number7
DOIs
StatePublished - Jul 2011

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Pande, M., Hur, J., Hong, Y., Backus, C., Hayes, J. M., Oh, S. S., Kretzler, M., & Feldman, E. L. (2011). Transcriptional profiling of diabetic neuropathy in the BKS db/db mouse: A model of type 2 diabetes. Diabetes, 60(7), 1981-1989. https://doi.org/10.2337/db10-1541