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

Olsson, Anders H LU ; Yang, Beatrice LU ; Hall, Elin LU ; Taneera, Jalal LU ; Salehi, S Albert LU ; Dekker Nitert, Marloes LU and Ling, Charlotte LU (2011) In European Journal of Endocrinology 165. p.589-595
Abstract
OBJECTIVE:

Gene expression alterations, especially in target tissues of insulin, have been associated with type 2 diabetes (T2D). Here, 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 9 T2D donors using microarray.



RESULTS:

While the expected number of OXPHOS genes with reduced gene expression is 7.21 we identified 21 down-regulated OXPHOS genes in pancreatic islets from patients with T2D using microarray analysis. This... (More)
OBJECTIVE:

Gene expression alterations, especially in target tissues of insulin, have been associated with type 2 diabetes (T2D). Here, 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 9 T2D donors using microarray.



RESULTS:

While the expected number of OXPHOS genes with reduced gene expression is 7.21 we identified 21 down-regulated 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 using a Χ(2)-test with p = 1.52•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 down-regulated in islets from patients with T2D compared with non-diabetic donors using qRT-PCR (p≤0.01). Furthermore, HbA1c levels correlated negatively with gene expression of NDUFA5, COX11 and ATP6V1H (p less than 0.05). Gene expression of NDUFA5, NDUFA10, COX11 and ATP6V1H correlated positively with glucose-stimulated insulin secretion (p less than 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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Endocrinology
volume
165
pages
589 - 595
publisher
Society of the European Journal of Endocrinology
external identifiers
  • wos:000295958700013
  • pmid:21775499
  • scopus:80052618443
ISSN
1479-683X
DOI
10.1530/EJE-11-0282
language
English
LU publication?
yes
id
efa73bc5-a8f7-46a9-990b-a10d778310dd (old id 2058435)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21775499?dopt=Abstract
date added to LUP
2011-08-01 20:17:52
date last changed
2017-11-12 04:08:53
@article{efa73bc5-a8f7-46a9-990b-a10d778310dd,
  abstract     = {OBJECTIVE:<br/><br>
Gene expression alterations, especially in target tissues of insulin, have been associated with type 2 diabetes (T2D). Here, 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.<br/><br>
<br/><br>
DESIGN AND METHODS:<br/><br>
Gene expression was analyzed in human pancreatic islets from 55 non-diabetic donors and 9 T2D donors using microarray.<br/><br>
<br/><br>
RESULTS:<br/><br>
While the expected number of OXPHOS genes with reduced gene expression is 7.21 we identified 21 down-regulated 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 using a Χ(2)-test with p = 1.52•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 down-regulated in islets from patients with T2D compared with non-diabetic donors using qRT-PCR (p≤0.01). Furthermore, HbA1c levels correlated negatively with gene expression of NDUFA5, COX11 and ATP6V1H (p less than 0.05). Gene expression of NDUFA5, NDUFA10, COX11 and ATP6V1H correlated positively with glucose-stimulated insulin secretion (p less than 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.<br/><br>
<br/><br>
CONCLUSION:<br/><br>
Pancreatic islets from patients with T2D show decreased expression of a set of OXPHOS genes, which may lead to impaired insulin secretion.},
  author       = {Olsson, Anders H and Yang, Beatrice and Hall, Elin and Taneera, Jalal and Salehi, S Albert and Dekker Nitert, Marloes and Ling, Charlotte},
  issn         = {1479-683X},
  language     = {eng},
  pages        = {589--595},
  publisher    = {Society of the European Journal of Endocrinology},
  series       = {European Journal of Endocrinology},
  title        = {Decreased expression of genes involved in oxidative phosphorylation in human pancreatic islets from patients with type 2 diabetes.},
  url          = {http://dx.doi.org/10.1530/EJE-11-0282},
  volume       = {165},
  year         = {2011},
}