Effects of altered glucokinase gene copy number on blood glucose homoeostasis.
Effects of altered glucokinase gene copy number on blood glucose homoeostasis.
复制标题
改变葡萄糖激酶基因拷贝数对血糖稳态的影响。
DOI：
10.1042/bst0250113
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发表时间：
1997
影响因子：
3.9
通讯作者：
Magnuson,MA
中科院分区：
文献类型：
--
作者：
Niswender,KD;Postic,C;Shiota,M;Jetton,TL;Magnuson,MA
葡萄糖激酶(GK)基因的表达是维持葡萄糖稳态所必需的。这种高-己糖激酶在肝脏和胰腺P细胞中都有表达[L-31，以及其他罕见的神经内分泌细胞类型，这些细胞可能也在葡萄糖稳态调节中发挥作用[4，5]。在人类中，GK基因的编码序列突变会导致青年2型糖尿病(MODY-2)，这是一种非胰岛素依赖型糖尿病[6-81.由于MODY-2是作为常染色体显性杂合子遗传的，其发病机制被认为是由于丢失了一个功能基因拷贝而导致GK活性降低[7，9-111]。由于目前尚不清楚这些细胞类型中GK活性降低实际上是如何导致糖尿病的，我们和其他人已经研究了改变小鼠GK基因功能拷贝数的后果([12-141；KD Niswender，M.Shiota，C.Postic，TL Jetton，B.Bennett，D.Piston，S.Efrat，A.D.Chemington和M.A.Magnuson，未发表的工作)。对这些小鼠模型的分析为干扰GK基因表达对葡萄糖稳态的影响提供了新的见解。
Glucokinase (GK) gene expression is essential for glucose homoeostasis. This high& hexokinase is expressed in both the liver and pancreatic P-cell [l-31, as well as in other rare neuraVneuroendocrine cell types that may also play a role in the regulation of glucose homoeostasis [4, 5]. In humans, coding sequence mutations in the GK gene cause maturity-onset diabetes of the young, type 2 (MODY-2), a form of non-insulin-dependent diabetes mellitus [6-81. Since MODY-2 is inherited as an autosoma1 dominant heterozygous trait, its pathogenesis is thought to be due to reduced GK activity from the loss of one functional gene copy [7, 9-111. Because it is not yet clear how diminished GK activity within these cell types actually causes diabetes, we and others have studied the consequences of altering the number of functional copies of the GK gene in mice ([12-141; KD Niswender, M. Shiota, C. Postic, TL Jetton, B. Bennett, D. Piston, S. Efrat, A. D. Chemington and M. A. Magnuson, unpublished work). Analysis of these mouse models provides new insights into the effects of perturbed GK gene expression on glucose homoeostasis.