title: Genes involved in oxidative phosphorylation are coordinately upregulated with fasting hyperglycaemia in livers of patients with type 2 diabetes.
abstract: OBJECTIVE
  Mitochondrial oxidative phosphorylation (OXPHOS) plays an important role in the pathophysiology of type 2 diabetes. Genes involved in OXPHOS have been reported to be down-regulated in skeletal muscle from patients with type 2 diabetes; however, hepatic regulation is unknown.
  
  
  METHODS
  We analysed expression of genes involved in OXPHOS from the livers of 14 patients with type 2 diabetes and 14 subjects with NGT using serial analysis of gene expression (SAGE) and DNA chip analysis. We evaluated the correlation between expression levels of genes involved in OXPHOS and the clinical parameters of individuals with type 2 diabetes and NGT.
  
  
  RESULTS
  Both gene analyses showed that genes involved in OXPHOS were significantly upregulated in the type 2 diabetic liver. In the SAGE analysis, tag count comparisons of mitochondrial transcripts showed that ribosomal RNAs (rRNA) were 3.5-fold over-expressed, and mRNAs were 1.2-fold over-expressed in the type 2 diabetes library. DNA chip analysis revealed that expression of genes involved in OXPHOS, which correlated with several nuclear factors, including estrogen-related receptor-alpha or peroxisome proliferator-activated receptor-gamma, was a predictor of fasting plasma glucose levels, independently of age, BMI, insulin resistance and fasting insulin levels (p = 0.04). Surprisingly, genes involved in OXPHOS did not correlate with peroxisome proliferator-activated receptor-gamma coactivator-1alpha or nuclear respiratory factor 1.
  
  
  CONCLUSIONS
  Our results indicate that upregulation of genes involved in OXPHOS in the liver, which are regulated by different mechanisms from genes in the skeletal muscle, is associated with fasting hyperglycaemia in patients with type 2 diabetes.
authors.affiliation: Deparment of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Misu
authors.forename: T
authors.initials: T
authors.lastname: Takamura
authors.forename: N
authors.initials: N
authors.lastname: Matsuzawa
authors.forename: A
authors.initials: A
authors.lastname: Shimizu
authors.forename: T
authors.initials: T
authors.lastname: Ota
authors.forename: M
authors.initials: M
authors.lastname: Sakurai
authors.forename: H
authors.initials: H
authors.lastname: Ando
authors.forename: K
authors.initials: K
authors.lastname: Arai
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: S
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000368:Aged; D003110:Colonic Neoplasms / Q000150:complications / Q000473:pathology; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D020224:Expressed Sequence Tags; D005215:Fasting; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000150:complications / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010085:Oxidative Phosphorylation; D013274:Stomach Neoplasms / Q000145:classification / Q000473:pathology
chemical_list: D017931:DNA Primers