A modest glucokinase overexpression in the liver promotes fed expression levels of glycolytic and lipogenic enzyme genes in the fasted state without altering SREBP-1c expression.
A modest glucokinase overexpression in the liver promotes fed expression levels of glycolytic and lipogenic enzyme genes in the fasted state without altering SREBP-1c expression.
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肝脏中适度的葡萄糖激酶过度表达可促进禁食状态下糖酵解和脂肪生成酶基因的进食表达水平，而不改变 SREBP-1c 表达。
DOI：
10.1023/a:1027306122336
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发表时间：
2003
影响因子：
4.3
通讯作者：
O'Doherty,RM
中科院分区：
文献类型：
--
作者：
Scott,DK;Collier,JJ;Doan,TTT;Bunnell,AS;Daniels,MC;Eckert,DT;O'Doherty,RM
对于碳水化合物和脂质稳态至关重要的肝脏基因受到胰岛素和葡萄糖代谢的调节。然而，胰岛素和葡萄糖对代谢基因表达调节的相对贡献在体内尚不清楚。为了解决这个问题，使用腺病毒介导的肝脏葡萄糖激酶过度表达来确定禁食或自由喂养的大鼠中肝脏葡萄糖代谢增加对基因表达的影响。在禁食状态下，3倍的葡萄糖激酶过度表达足以模拟进食诱导的丙酮酸激酶和乙酰辅酶A羧化酶mRNA水平的增加，证明葡萄糖代谢在体内调节这些基因中的主要作用。相反，葡萄糖激酶过表达无法模拟进食诱导的脂肪酸合酶、6-磷酸葡萄糖脱氢酶、肉毒碱棕榈酰转移酶 I 或 PEPCK mRNA 的改变，表明胰岛素是这些基因的主要调节因子。有趣的是，在禁食和进食状态下，葡萄糖激酶过度表达都会增加葡萄糖-6-磷酸酶 mRNA 的增加，这为在这些条件下该基因的体内葡萄糖信号传导对胰岛素信号传导的主导作用提供了证据。重要的是，葡萄糖激酶过表达不会改变体内甾醇调节元件结合蛋白1-c mRNA水平，并且葡萄糖信号传导不会改变该基因在原代肝细胞中的表达。我们得出的结论是，肝脏中葡萄糖激酶的适度过度表达足以改变代谢基因的表达，而不改变 SREBP-1c 的表达。
Hepatic genes crucial for carbohydrate and lipid homeostasis are regulated by insulin and glucose metabolism. However, the relative contributions of insulin and glucose to the regulation of metabolic gene expression are poorly definedin vivo. To address this issue, adenovirus-mediated hepatic overexpression of glucokinase was used to determine the effects of increased hepatic glucose metabolism on gene expression in fasted orad libitumfed rats. In the fasted state, a 3 fold glucokinase overexpression was sufficient to mimic feeding-induced increases in pyruvate kinase and acetyl CoA carboxylase mRNA levels, demonstrating a primary role for glucose metabolism in the regulation of these genesin vivo. Conversely, glucokinase overexpression was unable to mimic feeding-induced alterations of fatty acid synthase, glucose-6-phosphate dehydrogenase, carnitine palmitoyl transferase I or PEPCK mRNAs, indicating insulin as the primary regulator of these genes. Interestingly, glucose-6-phosphatase mRNA was increased by glucokinase overexpression in both the fasted and fed states, providing evidence, under these conditions, for the dominance of glucose over insulin signaling for this genein vivo. Importantly, glucokinase overexpression did not alter sterol regulatory element binding protein 1-c mRNA levelsin vivoand glucose signaling did not alter the expression of this gene in primary hepatocytes. We conclude that a modest hepatic overexpression of glucokinase is sufficient to alter expression of metabolic genes without changing the expression of SREBP-1c.