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学科主题基础医学
Evolution of Hepatic Glucose Metabolism: Liver-Specific Glucokinase Deficiency Explained by Parallel Loss of the Gene for Glucokinase Regulatory Protein (GCKR)
Wang, Zhao Yang1; Jin, Ling2; Tan, Huanran2; Irwin, David M.1,2,3
刊名PLOS ONE
2013-04-01
DOI10.1371/journal.pone.0060896
8期:4
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
资助者National Science Foundation of China (NSFC) ; Canadian Institutes of Health Research (CIHR) ; China-Canada Joint Health Research Initiative ; DMI ; National Science Foundation of China (NSFC) ; Canadian Institutes of Health Research (CIHR) ; China-Canada Joint Health Research Initiative ; DMI
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]GENOMIC DNA-SEQUENCES ; PHOSPHORYLATING ISOENZYMES ; SUBCELLULAR-LOCALIZATION ; MAMMALIAN GLUCOKINASE ; DIABETES-MELLITUS ; RAT-LIVER ; INSULIN ; HEXOKINASES ; VERTEBRATES ; IDENTIFICATION
英文摘要

Background: Glucokinase (GCK) plays an important role in the regulation of carbohydrate metabolism. In the liver, phosphorylation of glucose to glucose-6-phosphate by GCK is the first step for both glycolysis and glycogen synthesis. However, some vertebrate species are deficient in GCK activity in the liver, despite containing GCK genes that appear to be compatible with function in their genomes. Glucokinase regulatory protein (GCKR) is the most important post-transcriptional regulator of GCK in the liver; it participates in the modulation of GCK activity and location depending upon changes in glucose levels. In experimental models, loss of GCKR has been shown to associate with reduced hepatic GCK protein levels and activity.

Methodology/Principal Findings: GCKR genes and GCKR-like sequences were identified in the genomes of all vertebrate species with available genome sequences. The coding sequences of GCKR and GCKR-like genes were identified and aligned; base changes likely to disrupt coding potential or splicing were also identified.

Conclusions/Significance: GCKR genes could not be found in the genomes of 9 vertebrate species, including all birds. In addition, in multiple mammalian genomes, whereas GCKR-like gene sequences could be identified, these genes could not predict a functional protein. Vertebrate species that were previously reported to be deficient in hepatic GCK activity were found to have deleted (birds and lizard) or mutated (mammals) GCKR genes. Our results suggest that mutation of the GCKR gene leads to hepatic GCK deficiency due to the loss of the stabilizing effect of GCKR.

语种英语
所属项目编号81061120525 ; CCI-109605
资助者National Science Foundation of China (NSFC) ; Canadian Institutes of Health Research (CIHR) ; China-Canada Joint Health Research Initiative ; DMI ; National Science Foundation of China (NSFC) ; Canadian Institutes of Health Research (CIHR) ; China-Canada Joint Health Research Initiative ; DMI
WOS记录号WOS:000316930900082
引用统计
被引频次:8[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67112
专题基础医学院_药理学系
作者单位1.Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada
2.Peking Univ, Hlth Sci Ctr, Dept Pharmacol, Beijing 100871, Peoples R China
3.Univ Toronto, Banting & Best Diabet Ctr, Toronto, ON M5G 1L5, Canada
推荐引用方式
GB/T 7714
Wang, Zhao Yang,Jin, Ling,Tan, Huanran,et al. Evolution of Hepatic Glucose Metabolism: Liver-Specific Glucokinase Deficiency Explained by Parallel Loss of the Gene for Glucokinase Regulatory Protein (GCKR)[J]. PLOS ONE,2013,8(4).
APA Wang, Zhao Yang,Jin, Ling,Tan, Huanran,&Irwin, David M..(2013).Evolution of Hepatic Glucose Metabolism: Liver-Specific Glucokinase Deficiency Explained by Parallel Loss of the Gene for Glucokinase Regulatory Protein (GCKR).PLOS ONE,8(4).
MLA Wang, Zhao Yang,et al."Evolution of Hepatic Glucose Metabolism: Liver-Specific Glucokinase Deficiency Explained by Parallel Loss of the Gene for Glucokinase Regulatory Protein (GCKR)".PLOS ONE 8.4(2013).
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