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Genes involved in oxidative phosphorylation are coordinately upregulated with fasting hyperglycaemia in livers of patients with type 2 diabetes
- Source :
- Diabetologia. 50:268-277
- Publication Year :
- 2006
- Publisher :
- Springer Science and Business Media LLC, 2006.
-
Abstract
- Mitochondrial oxidative phosphorylation (OXPHOS) plays an important role in the pathophysiology of type 2 diabetes. Genes involved in OXPHOS have been reported to be down-regulated in skeletal muscle from patients with type 2 diabetes; however, hepatic regulation is unknown.We analysed expression of genes involved in OXPHOS from the livers of 14 patients with type 2 diabetes and 14 subjects with NGT using serial analysis of gene expression (SAGE) and DNA chip analysis. We evaluated the correlation between expression levels of genes involved in OXPHOS and the clinical parameters of individuals with type 2 diabetes and NGT.Both gene analyses showed that genes involved in OXPHOS were significantly upregulated in the type 2 diabetic liver. In the SAGE analysis, tag count comparisons of mitochondrial transcripts showed that ribosomal RNAs (rRNA) were 3.5-fold over-expressed, and mRNAs were 1.2-fold over-expressed in the type 2 diabetes library. DNA chip analysis revealed that expression of genes involved in OXPHOS, which correlated with several nuclear factors, including estrogen-related receptor-alpha or peroxisome proliferator-activated receptor-gamma, was a predictor of fasting plasma glucose levels, independently of age, BMI, insulin resistance and fasting insulin levels (p = 0.04). Surprisingly, genes involved in OXPHOS did not correlate with peroxisome proliferator-activated receptor-gamma coactivator-1alpha or nuclear respiratory factor 1.Our results indicate that upregulation of genes involved in OXPHOS in the liver, which are regulated by different mechanisms from genes in the skeletal muscle, is associated with fasting hyperglycaemia in patients with type 2 diabetes.
- Subjects :
- Male
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
Type 2 diabetes
Oxidative phosphorylation
Biology
Oxidative Phosphorylation
Downregulation and upregulation
Stomach Neoplasms
Internal medicine
Gene expression
Internal Medicine
medicine
Humans
Serial analysis of gene expression
Gene
Aged
DNA Primers
Expressed Sequence Tags
Liver Neoplasms
Skeletal muscle
Fasting
Middle Aged
medicine.disease
Pathophysiology
medicine.anatomical_structure
Endocrinology
Diabetes Mellitus, Type 2
Liver
Hyperglycemia
Colonic Neoplasms
Female
Subjects
Details
- ISSN :
- 14320428 and 0012186X
- Volume :
- 50
- Database :
- OpenAIRE
- Journal :
- Diabetologia
- Accession number :
- edsair.doi.dedup.....22130de5f8188a3e02b50dcd9b1d3e2a