title: Expression profile of mitrogen-activated protein kinase (MAPK) signaling genes in the skeletal muscle & liver of rat with type 2 diabetes: role in disease pathology.
abstract: OBJECTIVE
  Type 2 diabetes (T2D) is characterized as hyperglycaemia caused by defects in insulin secretion, and it affects target tissues, such as skeletal muscle, liver and adipose tissue. Therefore, analyzing the changes of gene expression profiles in these tissues is important to elucidate the pathogenesis of T2D. We, therefore, measured the gene transcript alterations in liver and skeletal muscle of rat with induced T2D, to detect differentially expressed genes in liver and skeletal muscle and perform gene-annotation enrichment analysis.
  
  
  METHODS
  In the present study, skeletal muscle and liver tissue from 10 streptozotocin-induced diabetic rats and 10 control rats were analyzed using gene expression microarrays. KEGG pathways enriched by differentially expressed genes (DEGs) were identified by WebGestalt Expander and GATHER software. DEGs were validated by the method of real-time PCR and western blot.
  
  
  RESULTS
  From the 9,929 expressed genes across the genome, 1,305 and 997 differentially expressed genes (DEGs, P<0.01) were identified in comparisons of skeletal muscle and liver, respectively. Large numbers of DEGs (200) were common in both comparisons, which was clearly more than the predicted number (131 genes, P<0.001). For further interpretation of the gene expression data, three over-representation analysis softwares (WebGestalt, Expander and GATHER) were used. All the tools detected one KEGG pathway (MAPK signaling) and two GO (gene ontology) biological processes (response to stress and cell death), with enrichment of DEGs in both tissues. In addition, PPI (protein-protein interaction) networks constructed using human homologues not only revealed the tendency of DEGs to form a highly connected module, but also suggested a "hub" role of p38-MAPK-related genes (such as MAPK14) in the pathogenesis of T2D.
  
  
  CONCLUSIONS
  Our results indicated the considerably aberrant MAPK signaling in both insulin-sensitive tissues of T2D rat, and that the p38 may play a role as a common "hub" in the gene module response to hyperglycaemia. Furthermore, our research pinpoints the role of several new T2D-associated genes (such as Srebf1 and Ppargc1) in the human population.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Tang
authors.forename: Libin
authors.initials: L
authors.lastname: Deng
authors.forename: Huangui
authors.initials: H
authors.lastname: Xiong
authors.forename: Guilin
authors.initials: G
authors.lastname: Li
authors.forename: Jiari
authors.initials: J
authors.lastname: Lin
authors.forename: Shuangmei
authors.initials: S
authors.lastname: Liu
authors.forename: Jinyan
authors.initials: J
authors.lastname: Xie
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Fanjun
authors.initials: F
authors.lastname: Kong
authors.forename: Guihua
authors.initials: G
authors.lastname: Tu
authors.forename: Haiying
authors.initials: H
authors.lastname: Peng
authors.affiliation: Department of Physiology, Medical School of Nanchang University, Nanchang, China.
authors.forename: Shangdong
authors.initials: S
authors.lastname: Liang
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics* / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D008099:Liver / Q000378:metabolism / Q000473:pathology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000096:biosynthesis* / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D051381:Rats; D015398:Signal Transduction
chemical_list: D007328:Insulin; D020929:Mitogen-Activated Protein Kinase Kinases