Lund University is celebrating 350 years. Read more on lunduniversity.lu.se

Menu

Javascript is not activated in your browser. This website needs javascript activated to work properly.
You are here

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

Author:
  • Anders H Olsson
  • Beatrice Yang
  • Elin Hall
  • Jalal Taneera
  • S Albert Salehi
  • Marloes Dekker Nitert
  • Charlotte Ling
Publishing year: 2011
Language: English
Pages: 589-595
Publication/Series: European Journal of Endocrinology
Volume: 165
Document type: Journal article
Publisher: Society of the European Journal of Endocrinology

Abstract english

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.

Keywords

  • Endocrinology and Diabetes

Other

Published
  • Diabetes and Endocrinology
  • Epigenetics and Diabetes
  • Islet cell physiology
  • ISSN: 1479-683X
E-mail: beatrice.yang [at] med.lu.se

Research student

Epigenetics and Diabetes

33

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00