Transcriptomic analysis of insulin-sensitive tissues from anti-diabetic drug treated ZDF rats, a T2DM animal model

PLoS One. 2013 Jul 26;8(7):e69624. doi: 10.1371/journal.pone.0069624. Print 2013.

Abstract

Gene expression changes have been associated with type 2 diabetes mellitus (T2DM); however, the alterations are not fully understood. We investigated the effects of anti-diabetic drugs on gene expression in Zucker diabetic fatty (ZDF) rats using oligonucleotide microarray technology to identify gene expression changes occurring in T2DM. Global gene expression in the pancreas, adipose tissue, skeletal muscle, and liver was profiled from Zucker lean control (ZLC) and anti-diabetic drug treated ZDF rats compared with those in ZDF rats. We showed that anti-diabetic drugs regulate the expression of a large number of genes. We provided a more integrated view of the diabetic changes by examining the gene expression networks. The resulting sub-networks allowed us to identify several biological processes that were significantly enriched by the anti-diabetic drug treatment, including oxidative phosphorylation (OXPHOS), systemic lupus erythematous, and the chemokine signaling pathway. Among them, we found that white adipose tissue from ZDF rats showed decreased expression of a set of OXPHOS genes that were normalized by rosiglitazone treatment accompanied by rescued blood glucose levels. In conclusion, we suggest that alterations in OXPHOS gene expression in white adipose tissue may play a role in the pathogenesis and drug mediated recovery of T2DM through a comprehensive gene expression network study after multi-drug treatment of ZDF rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cluster Analysis
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / genetics*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics*
  • Disease Models, Animal
  • Gene Expression Profiling*
  • Gene Regulatory Networks / drug effects
  • Glucose Tolerance Test
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Insulin / pharmacology*
  • Male
  • Organ Specificity / drug effects
  • Organ Specificity / genetics*
  • Oxidative Phosphorylation / drug effects
  • Rats
  • Rats, Zucker
  • Real-Time Polymerase Chain Reaction
  • Reproducibility of Results
  • Transcription, Genetic / drug effects

Substances

  • Hypoglycemic Agents
  • Insulin

Grants and funding

This work was supported by the grant from the Korea Food and Drug Administration (1470001450) to SJK and KKS; a grant by National Research Foundation (NRF), which is funded by the Korean government (MEST)(2012055344 and 2012M3A9D1054622) to SJK. This study was also partially supported by the Research Institute for Veterinary Science, Seoul National University. SJK, KYN, SJH, and KIY were supported by the Brain Korea 21 Program for Veterinary Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.