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学科主题: 基础医学
题名:
Differential expression of genes and changes in glucose metabolism in the liver of liver-specific glucokinase gene knockout mice
作者: Wang, Rong1; Gao, Hui1; Xu, Wei1; Li, Hui1; Mao, Yiqing1; Wang, Yi1; Guo, Tingting1; Wang, Xi1; Song, Rongjing1; Li, Zhixin2; Irwin, David M.1,3; Niu, Gang4; Tan, Huanran1
关键词: Glucokinase (GCK) ; MODY2 ; Differentially expressed genes ; Liver
刊名: GENE
发表日期: 2013-03-10
DOI: 10.1016/j.gene.2012.12.036
卷: 516, 期:2, 页:248-254
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Genetics & Heredity
研究领域[WOS]: Genetics & Heredity
关键词[WOS]: DEPENDENT DIABETES-MELLITUS ; HEPATIC GLYCOGEN-SYNTHESIS ; BETA-CELL GLUCOKINASE ; PHOSPHOENOLPYRUVATE CARBOXYKINASE ; CHOLESTEROL ACYLTRANSFERASE ; NEONATAL-RAT ; ANIMAL-MODEL ; INSULIN ; MUTATIONS ; YOUNG
英文摘要:

To investigate the role of liver-specific expression of glucokinase (GCK) in the pathogenesis of hyperglycemia and to identify candidate genes involved in mechanisms of the onset and progression of maturity onset diabetes of the young, type 2 (MODY-2), we examined changes in biochemical parameters and gene expression in GCK knockout (gck(w/-)) and wild-type (gck(w/w)) mice as they aged. Fasting blood glucose levels were found to be significantly higher in the gck(w/-) mice, compared to age-matched gck(w/w) mice, at all ages (P<0.05), except at 2 weeks. GCK activity of gck(w/-) mice was about 50% of that of wild type (gck(w/w)) mice (P<0.05). Glycogen content at 4 and 40 weeks of age was lower in gck(w/-) mice compared to gck(w/w) mice. Differentially expressed genes in the livers of 2 and 26 week-old liver-specific GCK knockout (gck(w/-)) mice were identified by suppression subtractive hybridization (SSH), which resulted in the identification of phosphoenolpyruvatecarboxykinase (PEPCK, also called PCK1) and Sterol O-acyltransferase 2 (SOAT2) as candidate genes involved in pathogenesis. The expressions of PEPCK and SOAT2 along with glycogen phosphorylase (GP) and glycogen synthase (GS) were then examined in GCK knockout (gck(w/-)) and wild-type (gck(w/w)) mice at different ages. Changes in PEPCK mRNA levels were confirmed by real-time RT-PCR, while no differences in the levels of expression of SOAT2 or GS were observed in age-matched GCK knockout (gck(w/-)) and wild-type (gck(w/w)) mice. GP mRNA levels were decreased in 40-week old gck(w/-) mice compared to age-matched gck(w/w) mice. Changes in gluconeogenesis, delayed development of GCK and impaired hepatic glycogen synthesis in the liver potentially lead to the onset and progression of MODY2. (C) 2012 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 30772603 ; 81061120525 ; 2006BAF07B01 ; 2009BAK61B04 ; 2009ZX09301-010
项目资助者: National Natural Science Foundation of China ; CIHR-NSFC China-Canada Joint Health Research Initiative Program from the National Natural Science Foundation of China ; National Key Scientific and Technology Program and the National "211 Project" in Peking University
WOS记录号: WOS:000315430900008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64669
Appears in Collections:基础医学院_药理学系_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Dept Pharmacol, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Integrated Tradit Chinese & Western Med, Beijing 100191, Peoples R China
3.Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada
4.Beijing N&N Genetech Co, Beijing 100082, Peoples R China

Recommended Citation:
Wang, Rong,Gao, Hui,Xu, Wei,et al. Differential expression of genes and changes in glucose metabolism in the liver of liver-specific glucokinase gene knockout mice[J]. GENE,2013,516(2):248-254.
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