Genes involved in oxidative phosphorylation are coordinately upregulated with fasting hyperglycaemia in livers of patients with type 2 diabetes
Genes involved in oxidative phosphorylation are coordinately upregulated with fasting hyperglycaemia in livers of patients with type 2 diabetes
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DOI：
10.1007/s00125-006-0489-8
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发表时间：
2007-02-01
期刊：
影响因子：
8.2
通讯作者：
Kaneko, S.
中科院分区：
文献类型：
--
作者：
Misu, H.;Takamura, T.;Kaneko, S.
目的/假设线粒体氧化磷酸化（OXPHOS）在2型糖尿病的病理生理学中起重要作用。参与OXPHOS的基因已被报道下调，从2型糖尿病患者的骨骼肌，但是，肝脏调节是unknown.Methods我们分析了参与OXPHOS的基因表达从14例2型糖尿病患者和14例NGT使用基因表达系列分析（SAGE）和DNA芯片分析。我们评估了参与OXPHOS的基因表达水平与2型糖尿病和NGT.Results的个体的临床参数之间的相关性，这两种基因分析表明，参与OXPHOS的基因在2型糖尿病肝脏中显著上调。在SAGE分析中，线粒体转录物的标签计数比较显示，在2型糖尿病文库中，核糖体RNA（rRNA）过表达3.5倍，mRNA过表达1.2倍。DNA芯片分析显示，OXPHOS相关基因的表达与几种核因子相关，包括雌激素相关受体-α或过氧化物酶体增殖物激活受体-γ，是空腹血糖水平的预测因子，与年龄、BMI、胰岛素抵抗和空腹胰岛素水平无关（p=0.04）。令人惊讶的是，参与OXPHOS的基因与过氧化物酶体增殖物激活受体-γ共激活因子-1 α或核呼吸因子1无关。结论/解释我们的研究结果表明，肝脏中参与OXPHOS的基因上调与2型糖尿病患者的空腹高血糖相关，这些基因受骨骼肌中基因不同机制的调控。
Aims/hypothesis 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.Methods 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.Results 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-1 alpha or nuclear respiratory factor 1.Conclusions/interpretation 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.