Rosiglitazone treatment reduces diabetic neuropathy in streptozotocin-treated DBA/2J mice.
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 the development of thermal hypoalgesia. Two novel transcription factor binding modules were identified that may control genes correlated to changes in DN after Rosi treatment: SP1F_ZBPF and EGRF_EGRF. These targets may be useful in designing drugs with the same efficacy as Rosi in treating DN but with fewer undesirable effects.
Wiggin
Timothy D
TD
University of Michigan, Department of Neurology, 5017 Basic Science Research Building, 109 Zina Pitcher Road, Ann Arbor, Michigan 48109-2200, USA.
Kretzler
Matthias
M
Pennathur
Subramaniam
S
Sullivan
Kelli A
KA
Brosius
Frank C
FC
Feldman
Eva L
EL
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000235:genetics*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D023281:Genomics; D013006:Growth Hormone / Q000097:blood; D006930:Hyperalgesia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000502:physiology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D013006:Growth Hormone