title: Decreased expression of genes involved in oxidative phosphorylation in human pancreatic islets from patients with type 2 diabetes.
abstract: OBJECTIVE
  Gene expression alterations, especially in target tissues of insulin, have been associated with type 2 diabetes (T2D). In this study, we examined if genes involved in oxidative phosphorylation (OXPHOS) show differential gene expression and DNA methylation in pancreatic islets from patients with T2D compared with non-diabetic donors.
  
  
  METHODS
  Gene expression was analyzed in human pancreatic islets from 55 non-diabetic donors and nine T2D donors using microarray.
  
  
  RESULTS
  While the expected number of OXPHOS genes with reduced gene expression is 7.21, we identified 21 downregulated OXPHOS genes in pancreatic islets from patients with T2D using microarray analysis. This gives a ratio of observed over expected OXPHOS genes of 26.37 by a χ(2)-test with P=2.81 × 10(-7). The microarray data was validated by qRT-PCR for four selected OXPHOS genes: NDUFA5, NDUFA10, COX11, and ATP6V1H. All four OXPHOS genes were significantly downregulated in islets from patients with T2D compared with non-diabetic donors using qRT-PCR (P ≤ 0.01). Furthermore, HbAlc levels correlated negatively with gene expression of NDUFA5, COX11, and ATP6V1H (P<0.05). Gene expression of NDUFA5, NDUFA10, COX11, and ATP6V1H correlated positively with glucose-stimulated insulin secretion (P<0.03). Finally, DNA methylation was analyzed upstream of the transcription start for NDUFA5, COX11, and ATP6V1H. However, none of the analyzed CpG sites in the three genes showed differences in DNA methylation in islets from donors with T2D compared with non-diabetic donors.
  
  
  CONCLUSIONS
  Pancreatic islets from patients with T2D show decreased expression of a set of OXPHOS genes, which may lead to impaired insulin secretion.
authors.affiliation: Department of Clinical Sciences, Lund University Diabetes Centre, CRC, Scania University Hospital, Malmo, Sweden.
authors.forename: Anders H
authors.initials: AH
authors.lastname: Olsson
authors.forename: Beatrice T
authors.initials: BT
authors.lastname: Yang
authors.forename: Elin
authors.initials: E
authors.lastname: Hall
authors.forename: Jalal
authors.initials: J
authors.lastname: Taneera
authors.forename: Albert
authors.initials: A
authors.lastname: Salehi
authors.forename: Marloes Dekker
authors.initials: MD
authors.lastname: Nitert
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ling
mesh_terms: D000328:Adult; D000368:Aged; D000079922:Copper Transport Proteins; D019175:DNA Methylation; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D045222:Electron Transport Chain Complex Proteins; D003576:Electron Transport Complex IV / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins; D009245:NADH Dehydrogenase / Q000235:genetics; D010085:Oxidative Phosphorylation; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C484188:COX11 protein, human; D000079922:Copper Transport Proteins; D045222:Electron Transport Chain Complex Proteins; D024101:Mitochondrial Proteins; C508060:NDUFA5 protein, human; D012313:RNA; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV