title: Tissue-specific differences in mitochondrial DNA content in type 2 diabetes.
abstract: BACKGROUND
  To investigate whether the effect of hyperglycemia on mitochondrial DNA (mtDNA) content is tissue-specific.
  
  
  METHODS
  We compared the mtDNA contents in leg muscle, blood vessel, and peripheral leucocytes in seventeen patients with type 2 diabetes (T2DM) with those of seven controls. We measured 8-hydroxydeoxyguanosine (8-OHdG) expression in the muscles and thiobarbituric acid reactive substance (TBARS) in sera to evaluate oxidative stress. Immunohistochemical detection of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1-α), mitochondrial transcription factor A (Tfam), and apoptosis were performed in the muscle tissue.
  
  
  RESULTS
  The mtDNA copy number was highest in muscle tissue, followed by blood vessel tissue, and lowest in leucocytes in both the diabetic and control subjects. The diabetic patients had less mtDNA content in the muscle than the controls (2.86±0.33 vs. 3.20±0.14, P=0.025), but more mtDNA content in the leucocytes (2.25±0.26 vs. 1.98±0.06, P=0.04). In both groups, there was a positive correlation between muscle tissue mtDNA content and the expression of 8-OHdG. Patients with T2DM had significantly increased 8-OHdG and TUNEL labeling index and non-significant increases in the expression of PGC1-α and Tfam.
  
  
  CONCLUSIONS
  Oxidative stress stimulates mitochondrial biogenesis but induces a greater degree of apoptosis in diabetic patients, resulting in a decrease in muscle tissue mtDNA content.
authors.affiliation: Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Ching-Jung
authors.initials: CJ
authors.lastname: Hsieh
authors.forename: Shao-Wen
authors.initials: SW
authors.lastname: Weng
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Liou
authors.forename: Tsu-Kung
authors.initials: TK
authors.lastname: Lin
authors.forename: Jin-Bor
authors.initials: JB
authors.lastname: Chen
authors.forename: Mao-Meng
authors.initials: MM
authors.lastname: Tiao
authors.forename: Yun-Ting
authors.initials: YT
authors.lastname: Hung
authors.forename: I-Ya
authors.initials: IY
authors.lastname: Chen
authors.forename: Wen-Te
authors.initials: WT
authors.lastname: Huang
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D004272:DNA, Mitochondrial / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D016133:Polymerase Chain Reaction
chemical_list: D004272:DNA, Mitochondrial