DNA microarray analysis of type 2 diabetes-related genes co-regulated between white blood cells and livers of diabetic Otsuka long-evans Tokushima fatty (OLETF) rats
DNA microarray analysis of type 2 diabetes-related genes co-regulated between white blood cells and livers of diabetic Otsuka long-evans Tokushima fatty (OLETF) rats
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DOI：
10.1248/bpb.30.763
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发表时间：
2007-04-01
影响因子：
2
通讯作者：
Harashima, Hideyoshi
中科院分区：
文献类型：
--
作者：
Hayashi, Yasuhiro;Iida, Shinya;Harashima, Hideyoshi
在先前的研究中，我们假设一些2型糖尿病易感基因可能在大冢长埃文斯德岛脂肪（OLETF）大鼠的白色血细胞（WBC）中上调/下调，反映了它们在糖尿病发作前在主要胰岛素靶组织（如肝脏）中的上调/下调。我们确定了57个预测糖尿病的潜在候选基因。在这项研究中，我们通过将实验条件从糖尿病发作前（6周）扩展到糖尿病发作后（24周），进一步验证了这一假设，即2型糖尿病易感基因在WBC中共调节，反映了它们在肝脏中的表达。使用大鼠寡核苷酸DNA微阵列，我们发现48个基因的上调/下调OLETF大鼠相比，控制Long-Evans德岛大冢（LETO）大鼠在白细胞和肝脏空腹或胰岛素给药条件下。分别在空腹和胰岛素给药条件下，WBC和肝脏中分别有29个和33个基因上调/下调。空腹条件下29个基因中的8个和胰岛素给药条件下33个基因中的12个已被报道为2型糖尿病易感基因，其余基因尚未被报道与2型糖尿病相关。这些结果支持了我们的假设，即白细胞中2型糖尿病相关基因的表达水平反映了糖尿病发病后肝脏中的表达水平。
In a previous study, we hypothesized that some type 2 diabetes mellitus susceptible genes may be up/down-regulated in white blood cells (WBC) of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, reflecting their up/down-regulation in major insulin-target tissues such as the liver before the onset of diabetes. We identified 57 potential candidate genes for predicting diabetes. In this study, we examined this hypothesis further by extending the experimental conditions from before the onset (6 weeks) to after the onset (24 weeks) of diabetes that type 2 diabetes mellitus susceptible genes are co-regulated in WBC, reflecting their expression in the liver. Using rat oligo DNA microarrays, we found that 48 genes are up/down-regulated in OLETF rats compared to control Long-Evans Tokushima Otsuka (LETO) rats in WBC and liver under fasting or insulin administration conditions. Twenty nine and 33 genes were up/down-regulated in both WBC and livers, respectively, under fasting and insulin administration conditions, respectively. Eight out of 29 genes in fasting condition and 12 out of 33 genes in insulin administration conditions have been reported to be type 2 diabetes mellitus susceptible genes and the remainder have not been reported to be related to type 2 diabetes mellitus. These results support our hypothesis that the expression levels of type 2 diabetes mellitus related genes in WBC are reflective of those in the liver after the onset of diabetes.