|
|
|
|
| 衰老大鼠肝葡萄糖促进因子的过度甲基化潜在的致糖尿病作用 |
|
|
|
|
|
| Hypermethylation of hepatic Gck promoter in ageing rats contributes to diabetogenic potential |
|
|
|
|
|
| Jiang M.H., Fei J., Lan M.S., Lu Z.P., Liu M., Fan W.W., Gao X., Lu D.R. 2009/5/29 18:38:57 |
|
|
【发表评论】
|
|
|
|
|
打印|
推荐给好友
|
|
|
Diabetologia, 2008, Volume 51, Issue 8
|
|
|
|
|
|
|
| Aims/hypothesis: Hepatic glucokinase (GCK) is a key enzyme in glucose utilisation. Downregulation of its activity is associated with insulin resistance and type 2 diabetes mellitus. However, it is unknown whether hepatic Gck expression is influenced by age and is involved in ageing-mediated diabetes, and whether the degree of methylation of the hepatic Gck promoter is correlated with the transcription of Gck. To address the question, we evaluated hepatic Gck transcription and promoter methylation in young (14 weeks), adult (40 weeks) and aged (80 weeks) rats. Methods: Hepatic glycogen, Gck expression and the kinase activity of GCK were measured in three age groups. The CpG methylation status was determined by both bisulphite direct sequencing and clone sequencing of the PCR amplificates of Gck promoter. The causal relationship between Gck methylation and mRNA expression was confirmed by treating rat primary hepatocytes with 5-aza-2′-deoxycytidine (5-Aza-CdR). Results: We have shown an age-associated decline in hepatic glycogen, Gck expression levels and the kinase activity of hepatic GCK. The eleven CpG sites studied displayed age-related progressive methylation changes in hepatic Gck promoter, which were confirmed by two methods: direct and clone sequencing. After 5-Aza-CdR treatment of rat primary hepatocytes, there was a fourfold increase in Gck expression. Conclusions/interpretation: Our results demonstrate that an age-related increase in methylation is negatively associated with hepatic Gck expression, suggesting that DNA methylation could be involved in increasing age-dependent susceptibility to hepatic insulin resistance and diabetes. Thus, the epigenetic modification of the hepatic Gck promoter may represent an important marker for diabetogenic potential during the ageing process. © 2008 Springer-Verlag. |
|
|
|
|
|
|
| Correspondence Address: Lu, D. R.; State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, 220 Handan Road, Shanghai 200433, China; email: drlu@fudan.edu.cn |
|
|
|
|
|
|
|
|
|
|
|
请登录后发表评论，点击此处登录。
|
|
|
 疾病资源中心
摘自：《西氏内科学》，第23版
患者女性，21岁，因干咳、间歇性气促2个月到急诊科就诊。开始症状为上呼吸道感染引起的鼻塞、流涕和咳嗽。医生检查后开了抗生素。服药后鼻部症状缓解，但仍有轻微干咳和呼吸困难。其他症状包括疲劳和焦虑。否认发热、体重减轻、胸痛、端坐呼吸、气喘、鼻后滴漏、胃灼热以及神经系统症状。
医学数据库
|
