Transcriptional Profiling of Diabetic Neuropathy in the BKS db/db Mouse: A Model of Type 2 Diabetes
Diabetes, 2011•Am Diabetes Assoc
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 …
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 …
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.
Am Diabetes Assoc