Clock gene expression in peripheral leucocytes of patients with type 2 diabetes
Clock gene expression in peripheral leucocytes of patients with type 2 diabetes
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DOI：
10.1007/s00125-008-1194-6
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发表时间：
2009-02-01
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：
Ando, H.;Takamura, T.;Kaneko, S.
最近的研究表明，生物钟功能与2型糖尿病等代谢性疾病的发生有关系。从8名糖尿病患者和6名比较年轻的非糖尿病志愿者在9：00、15：00、21：00和03：00采集外周血白细胞(研究1)，从12名男性糖尿病患者和14名年龄匹配的男性志愿者(研究2)在09：00采集外周血白细胞。时钟基因(Clock、BMAL1[又称ARNTL]、PER1、PER2、PER3和CRY1)的转录水平通过实时定量聚合酶链式反应测定。在研究1中，BMAL1、PER1、PER2和PER3在所有14个个体的白细胞中的表达模式都表现出24小时的节律性。在一个或多个时间点，糖尿病患者的这些mRNAs的表达水平显著低于非糖尿病患者(p<；0.05)。此外，糖尿病患者PER1和PER3基因表达节律的幅度有降低的趋势。在研究2中，糖尿病患者外周血白细胞BMAL1、PER1和PER3的转录水平显著低于对照组(p<；0.05)，且其转录水平与HbA(1c)水平呈负相关(rho=-0.47~-0.55，p<；0.05)。生物钟的损伤似乎与人类2型糖尿病的病理生理学密切相关。
Recent studies have demonstrated relationships between circadian clock function and the development of metabolic diseases such as type 2 diabetes. We investigated whether the peripheral circadian clock is impaired in patients with type 2 diabetes.Peripheral leucocytes were obtained from eight patients with diabetes and six comparatively young non-diabetic volunteers at 09:00, 15:00, 21:00 and 03:00 hours (study 1) and from 12 male patients with diabetes and 14 age-matched men at 09:00 hours (study 2). Transcript levels of clock genes (CLOCK, BMAL1 [also known as ARNTL], PER1, PER2, PER3 and CRY1) were determined by real-time quantitative PCR.In study 1, mRNA expression patterns of BMAL1, PER1, PER2 and PER3 exhibited 24 h rhythmicity in the leucocytes of all 14 individuals. The expression levels of these mRNAs were significantly (p < 0.05) lower in patients with diabetes than in non-diabetic individuals at one or more time points. Moreover, the amplitudes of mRNA expression rhythms of PER1 and PER3 genes tended to diminish in patients with diabetes. In study 2, leucocytes obtained from patients with diabetes expressed significantly (p < 0.05) lower transcript levels of BMAL1, PER1 and PER3 compared with leucocytes from control individuals, and transcript expression was inversely correlated with HbA(1c) levels (rho = -0.47 to -0.55, p < 0.05).These results suggest that rhythmic mRNA expression of clock genes is dampened in peripheral leucocytes of patients with type 2 diabetes. The impairment of the circadian clock appears to be closely associated with the pathophysiology of type 2 diabetes in humans.