Roles of hepatic glucokinase in intertissue metabolic communication: Examination of novel liver-specific glucokinase knockout mice
Roles of hepatic glucokinase in intertissue metabolic communication: Examination of novel liver-specific glucokinase knockout mice
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DOI：
10.1016/j.bbrc.2015.03.097
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发表时间：
2015-05-08
影响因子：
3.1
通讯作者：
Yamagata, Kazuya
中科院分区：
文献类型：
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作者：
Hayashi, Hirofumi;Sato, Yoshifumi;Yamagata, Kazuya
葡萄糖激酶主要在胰腺β细胞和肝细胞中表达，并催化葡萄糖磷酸化为葡萄糖-6-磷酸，这是糖酵解的限速步骤。为了更好地了解肝脏葡萄糖激酶的作用，我们通过切除肝脏特异性外显子1b产生Gck敲除小鼠。基因敲除小鼠表现出糖耐量受损、肝糖原含量降低以及肝脏中Pklr和Fas基因表达减少，表明肝脏葡萄糖激酶在葡萄糖代谢中起重要作用。据报道，肝葡萄糖激酶调节棕色脂肪组织（BAT）中产热相关基因的表达和胰岛素分泌对葡萄糖的反应。然而，肝脏特异性Gck敲除小鼠在正常饮食下既没有显示BAT中产热相关基因的表达改变，也没有显示β细胞的胰岛素分泌受损。这些结果表明，肝脏葡萄糖激酶的慢性抑制对组织间（肝脏至BAT以及肝脏至β细胞）代谢通讯的影响很小。(C)2015 Elsevier Inc. All rights reserved.
Glucokinase is expressed principally in pancreatic beta-cells and hepatocytes, and catalyzes the phosphorylation of glucose to glucose-6-phosphate, a rate-limiting step of glycolysis. To better understand the roles of hepatic glucokinase, we generated Gck knockout mice by ablating liver-specific exon 1b. The knockout mice exhibited impaired glucose tolerance, decreased hepatic glycogen content, and reduced Pklr and Fas gene expression in the liver, indicating that hepatic glucokinase plays important roles in glucose metabolism. It has also been reported that hepatic glucokinase regulates the expression of thermogenesis-related genes in brown adipose tissue (BAT) and insulin secretion in response to glucose. However, the liver-specific Gck knockout mice displayed neither altered expression of thermogenesis-related genes in BAT nor impaired insulin secretion by beta-cells under a normal chow diet. These results suggest that chronic suppression of hepatic glucokinase has a small influence on intertissue (liver-to-BAT as well as liver-to-beta-cell) metabolic communication. (C) 2015 Elsevier Inc. All rights reserved.