Rosiglitazone Treatment Reduces Diabetic Neuropathy in STZ treated DBA/2J mice
Authors Timothy D Wiggin, Matthias Kretzler, Subramaniam Pennathur, Kelli A. Sullivan,
Frank C Brosius, Eva L Feldman
Submitted By Eva Feldman on 4/4/2008
Status Published
Journal Endocrinology
Year 2008
Date Published 10/1/2008
Volume : Pages 149(10) : 4928 - 4937
PubMed Reference 18583417
Abstract Diabetic Neuropathy (DN) is a common complication of diabetes. Currently, there
is no drug treatment to prevent or slow the development of DN. Rosiglitazone
(Rosi) is a potent insulin sensitizer and may also slow the development of DN by
a mechanism independent of its effect on hyperglycemia. A two by two design was
used to test the effect of Rosi treatment on the development of DN.
Streptozotocin-induced diabetic DBA/2J mice were treated with Rosi. DN and
oxidative stress were quantified, and gene expression was profiled using the
Affymetrix Mouse Genome 430 2.0 microarray platform. An informatics approach
identified key regulatory elements activated by Rosi. Diabetic DBA/2J mice
developed severe hyperglycemia, DN and elevated oxidative stress. Rosi treatment
did not affect hyperglycemia but did reduce oxidative stress and prevented
development of thermal hypoalgesia. Two novel transcription factor binding
modules were identified that may control genes correlated to changes in DN
following Rosi treatment: SP1F_ZBPF and EGRF_EGRF. Rosi treatment reduced
oxidative stress and DN independent of its insulin sensitizing effects. Gene
expression profiling identified two novel targets activated by Rosi treatment.
These targets may be useful in designing drugs with the same efficacy as Rosi in
treating DN but with fewer undesirable effects.

Investigators with authorship
Frank BrosiusUniversity of Arizona
Eva FeldmanUniversity of Michigan
Matthias KretzlerUniversity of Michigan