Rosiglitazone treatment reduces diabetic neuropathy in streptozotocin-treated DBA/2J mice

Endocrinology. 2008 Oct;149(10):4928-37. doi: 10.1210/en.2008-0869. Epub 2008 Jun 26.

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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / genetics*
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / genetics*
  • Female
  • Gene Expression / drug effects
  • Genomics
  • Growth Hormone / blood
  • Hyperalgesia / drug therapy
  • Hypoglycemic Agents / pharmacology*
  • Male
  • Mice
  • Mice, Inbred DBA
  • Oligonucleotide Array Sequence Analysis
  • Oxidative Stress / drug effects
  • Promoter Regions, Genetic / physiology
  • Rosiglitazone
  • Thiazolidinediones / pharmacology*

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Thiazolidinediones
  • Rosiglitazone
  • Growth Hormone