| Title | Differential expression of genes and changes in glucose metabolism in the liver of liver-specific glucokinase gene knockout mice |
| Authors | Wang, Rong Gao, Hui Xu, Wei Li, Hui Mao, Yiqing Wang, Yi Guo, Tingting Wang, Xi Song, Rongjing Li, Zhixin Irwin, David M. Niu, Gang Tan, Huanran |
| Affiliation | Peking Univ, Hlth Sci Ctr, Dept Pharmacol, Beijing 100191, Peoples R China. Peking Univ, Hlth Sci Ctr, Dept Integrated Tradit Chinese & Western Med, Beijing 100191, Peoples R China. Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada. Beijing N&N Genetech Co, Beijing 100082, Peoples R China. Peking Univ, Hlth Sci Ctr, Dept Pharmacol, Sheng Li Bldg 232,38 Xue Yuan Rd, Beijing 100191, Peoples R China. |
| Keywords | Glucokinase (GCK) MODY2 Differentially expressed genes Liver DEPENDENT DIABETES-MELLITUS HEPATIC GLYCOGEN-SYNTHESIS BETA-CELL GLUCOKINASE PHOSPHOENOLPYRUVATE CARBOXYKINASE CHOLESTEROL ACYLTRANSFERASE NEONATAL-RAT ANIMAL-MODEL INSULIN MUTATIONS YOUNG |
| Issue Date | 2013 |
| Publisher | gene |
| Citation | GENE.2013,516,(2),248-254. |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/190614 |
| ISSN | 0378-1119 |
| DOI | 10.1016/j.gene.2012.12.036 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 医学部待认领 |
