Transcriptomic analysis of insulin-sensitive tissues from anti-diabetic drug treated ZDF rats, a T2DM animal model.
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.
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.
Yo Na
YN
Kim
Sangok
S
Kim
Il-Yong
IY
Kim
Jae Hoon
JH
Shin
Sooyoung
S
Cho
Sun Shin
SS
Yi
Wan Kyu
WK
Kim
Kyung-Sub
KS
Kim
Sanghyuk
S
Lee
Je Kyung
JK
Seong
D000818:Animals; D016000:Cluster Analysis; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000187:drug effects; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D051381:Rats; D011924:Rats, Zucker; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D014158:Transcription, Genetic / Q000187:drug effects
D007004:Hypoglycemic Agents; D007328:Insulin