Decreased expression of genes involved in oxidative phosphorylation in human pancreatic islets from patients with type 2 diabetes

Olsson, Anders H., Yang, Beatrice T., Hall, Elin., Taneera, Jalal, Salehi, Albert, Nitert, Marloes Dekker and Ling, Charlotte (2011) Decreased expression of genes involved in oxidative phosphorylation in human pancreatic islets from patients with type 2 diabetes. European Journal of Endocrinology, 165 4: 589-595. doi:10.1530/EJE-11-0282


Author Olsson, Anders H.
Yang, Beatrice T.
Hall, Elin.
Taneera, Jalal
Salehi, Albert
Nitert, Marloes Dekker
Ling, Charlotte
Title Decreased expression of genes involved in oxidative phosphorylation in human pancreatic islets from patients with type 2 diabetes
Journal name European Journal of Endocrinology   Check publisher's open access policy
ISSN 0804-4643
1479-683X
Publication date 2011-10
Sub-type Article (original research)
DOI 10.1530/EJE-11-0282
Volume 165
Issue 4
Start page 589
End page 595
Total pages 7
Place of publication Woodlands, Bristol, U.K.
Publisher BioScientifica
Collection year 2012
Language eng
Formatted 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.

Design and 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 χ2-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.

Conclusion Pancreatic islets from patients with T2D show decreased expression of a set of OXPHOS genes, which may lead to impaired insulin secretion.
Keyword Human skeletal-muscle
Insulin-secretion
beta-Cells
Mitochondria
Methylation
Dysfunction
Metabolism
Resistance
PPARGC1A
Lists
β-Cells
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 21 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 23 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Thu, 02 Feb 2012, 14:34:59 EST by Marloes Dekker on behalf of School of Medicine