PMID- 23922760 OWN - NLM STAT- MEDLINE DCOM- 20140429 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 7 DP - 2013 TI - Transcriptomic analysis of insulin-sensitive tissues from anti-diabetic drug treated ZDF rats, a T2DM animal model. PG - e69624 LID - 10.1371/journal.pone.0069624 [doi] LID - e69624 AB - 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. FAU - Kim, Yo Na AU - Kim YN AD - Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, Research Institute for Veterinary Science, BK21 Program for Veterinary Science, Seoul National University, Seoul, Korea. FAU - Kim, Sangok AU - Kim S FAU - Kim, Il-Yong AU - Kim IY FAU - Shin, Jae Hoon AU - Shin JH FAU - Cho, Sooyoung AU - Cho S FAU - Yi, Sun Shin AU - Yi SS FAU - Kim, Wan Kyu AU - Kim WK FAU - Kim, Kyung-Sub AU - Kim KS FAU - Lee, Sanghyuk AU - Lee S FAU - Seong, Je Kyung AU - Seong JK LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130726 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) SB - IM MH - Animals MH - Cluster Analysis MH - Diabetes Mellitus, Experimental/drug therapy/*genetics MH - Diabetes Mellitus, Type 2/*drug therapy/*genetics MH - Disease Models, Animal MH - *Gene Expression Profiling MH - Gene Regulatory Networks/drug effects MH - Glucose Tolerance Test MH - Hypoglycemic Agents/*pharmacology/therapeutic use MH - Insulin/*pharmacology MH - Male MH - Organ Specificity/drug effects/*genetics MH - Oxidative Phosphorylation/drug effects MH - Rats MH - Rats, Zucker MH - Real-Time Polymerase Chain Reaction MH - Reproducibility of Results MH - Transcription, Genetic/drug effects PMC - PMC3724940 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2013/08/08 06:00 MHDA- 2014/04/30 06:00 PMCR- 2013/07/26 CRDT- 2013/08/08 06:00 PHST- 2013/04/12 00:00 [received] PHST- 2013/06/12 00:00 [accepted] PHST- 2013/08/08 06:00 [entrez] PHST- 2013/08/08 06:00 [pubmed] PHST- 2014/04/30 06:00 [medline] PHST- 2013/07/26 00:00 [pmc-release] AID - PONE-D-13-15132 [pii] AID - 10.1371/journal.pone.0069624 [doi] PST - epublish SO - PLoS One. 2013 Jul 26;8(7):e69624. doi: 10.1371/journal.pone.0069624. Print 2013.