Regulation of rat liver glucose-6-phosphatase gene expression in different nutritional and hormonal states - Gene structure and 5'-flanking sequence
Regulation of rat liver glucose-6-phosphatase gene expression in different nutritional and hormonal states - Gene structure and 5'-flanking sequence
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DOI：
10.2337/diabetes.45.11.1563
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发表时间：
1996-11-01
期刊：
影响因子：
7.7
通讯作者：
Lange, AJ
中科院分区：
文献类型：
--
作者：
Argaud, D;Zhang, Q;Lange, AJ
大鼠肝脏葡萄糖-6-磷酸酶（Glu-6-phosphatase）催化亚基的mRNA水平受激素调节，与体内活性变化相称。胰岛素对谷氨酸-6-磷酸酶的mRNA水平产生显着的负作用。在胰岛素水平升高的进食和再进食状态下，该酶的mRNA水平和活性均较低。对糖尿病大鼠施用胰岛素也降低mRNA水平和Glu-6-β活性。在FAO肝癌细胞中，浓度为1 nmol/l的胰岛素完全克服糖皮质激素对Glu-6-β信息水平的刺激作用。FAO细胞对糖皮质激素的刺激反应是双相的，在激素添加后3和18 h观察到最大值（分别为1.6倍和3.3倍），8-（4-氯苯硫基）-cAMP（CPT-cAMP）在FAO细胞中3 h时导致Glu-6-cAMP mRNA增加4倍。大鼠肝Glu-6-Arg基因全长13个碱基，由5个外显子组成。与小鼠和人的基因相比，外显子-内含子结构是完全保守的，在大鼠和小鼠肝Glu-6-β cDNA中存在的0.5-kb的3 '非翻译区在本文报道的Glu-6-β基因中缺失，表明末端第五外显子或整个基因可能是重复的，启动子区含有一个位于-207位的核心CCAAT元件和一个位于-31位的TATAAA元件。在5 ′侧翼区已鉴定出几个可能的反应元件共有糖皮质激素反应元件位于碱基对-1552处，胰岛素反应序列的9/10匹配位于位置-1449处，cAMP应答元件的7/8匹配位于-164位。
The mRNA level of the catalytic subunit of rat liver glucose-6-phosphatase (Glu-6-Pase) was regulated by hormones commensurate with activity changes in vivo. Insulin exerts a dominant negative effect on the mRNA levels of Glu-6-Pase. Both mRNA levels and activities of the enzyme are low in the fed and refed state where insulin levels are elevated. Insulin administration to diabetic rats also decreases levels of mRNA and Glu-6-Pase activity, Insulin at a concentration of 1 nmol/l completely overcomes the stimulatory effect of glucocorticoids on Glu-6-Pase message levels in FAO hepatoma cells. The stimulatory response to glucocorticoid in FAO cells is biphasic, with maxima seen at 3 and 18 h after hormone addition (respectively 1.6- and 3.3-fold), 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) causes a fourfold increase in Glu-6-Pase mRNA at 3 h in FAO cells. The gene of rat liver Glu-6-Pase is 13 kilobases in length and comprised of 5 exons. The exon-intron structure is completely conserved when compared with the mouse and human genes, A 0.5-kb 3'-untranslated region, which is present in rat and mouse liver Glu-6-Pase cDNA, is absent in the Glu-6-Pase gene reported here, indicating the possible duplication of either the terminal fifth exon or the entire gene, The promoter region contains a consensus core CCAAT element at position -207 and a TATAAA at position -31, Several possible response elements have been identified in the 5'-flanking region (from a HindIII site at position -1641), A consensus glucocorticoid response element is located at base pair -1552, a 9/10 match of the insulin response sequence is located at position -1449, and a 7/8 match of the cAMP response element is located at position -164.