Developmental regulation of genes mediating murine brain glucose uptake

被引:34
作者
Khan, JY [1 ]
Rajakumar, RA [1 ]
McKnight, RA [1 ]
Devaskar, UP [1 ]
Devaskar, SU [1 ]
机构
[1] Univ Pittsburgh, Magee Womens Res Inst, Dept Pediat, Div Neonatol & Dev Biol, Pittsburgh, PA 15213 USA
关键词
glucose transporters; hexokinase; neurons; endothelial cells; glial cells;
D O I
10.1152/ajpregu.1999.276.3.R892
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
We examined the molecular mechanisms that mediate the developmental increase in murine whole brain 2-deoxyglucose uptake. Northern and Western blot analyses revealed an age-dependent increase in brain GLUT-1 (endothelial cell and glial) and GLUT-3 (neuronal) membrane-spanning facilitative glucose transporter mRNA and protein concentrations. Nuclear run-on experiments revealed that these developmental changes in GLUT-1 and -3 were regulated posttranscriptionally. In contrast, the mRNA and protein levels of the mitochondrially bound glucose phosphorylating hexokinase I enzyme were unaltered. However, hexokinase I enzyme activity increased in an age-dependent manner suggestive of a posttranslational modification that is necessary for enzymatic activation. Together, the postnatal increase in GLUT-1 and -3 concentrations and hexokinase I enzymatic activity led to a parallel increase in murine brain 2-deoxyglucose uptake. Whereas the molecular mechanisms regulating the increase in the three different gene products may vary, the age-dependent increase of all three constituents appears essential for meeting the increasing demand of the maturing brain to fuel the processes of cellular growth, differentiation, and neurotransmission.
引用
收藏
页码:R892 / R900
页数:9
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