Transcriptional regulation of the glucose-6-phosphatase gene by cAMP/vasoactive intestinal peptide in the intestine -: Role of HNF4α, CREM, HNF1α, and C/EBPα
Transcriptional regulation of the glucose-6-phosphatase gene by cAMP/vasoactive intestinal peptide in the intestine -: Role of HNF4α, CREM, HNF1α, and C/EBPα
复制标题
DOI：
10.1074/jbc.m603258200
复制
发表时间：
2006-10-20
影响因子：
4.8
通讯作者：
Rajas, Fabienne
中科院分区：
文献类型：
--
作者：
Gautier-Stein, Amandine;Zitoun, Carine;Rajas, Fabienne
葡萄糖异生在肝脏和肠中通过增加cAMP水平诱导。然而，肝脏和肠道葡萄糖的产生可能对葡萄糖稳态产生相反的影响。葡萄糖通过肠释放到门静脉中增加葡萄糖摄取并减少食物摄入。相反，肝脏产生的葡萄糖导致II型糖尿病的高血糖症。葡萄糖-6-磷酸酶（Glc 6-phosphatase，Glc 6-P）是肝脏和肠道中肠化生的关键酶。在这里，我们指定的cAMP/蛋白激酶A调节的Glc 6 β基因在肠道相比，肝脏。与肝脏相似，cAMP/蛋白激酶A调节的分子机制涉及cAMP反应元件结合蛋白、HNF 4 α、CAAT/增强子结合蛋白和HNF 1。与肝脏中的情况相反，我们发现CAAT/增强子结合蛋白和HNF 1的不同亚型有助于肠道中Glc 6 β基因的特异性调节。此外，我们表明，cAMP-反应元件结合调节剂特别有助于调节的Glc 6 β基因在肠道中，而不是在肝脏中。这些结果使我们能够识别Glc 6 β基因的精氨酸特异性调节剂，并提高对肠道与肝脏相比调节肠异生差异的理解。
Gluconeogenesis is induced in both the liver and intestine by increased cAMP levels. However, hepatic and intestinal glucose production can have opposite effects on glucose homeostasis. Glucose release into the portal vein by the intestine increases glucose uptake and reduces food intake. In contrast, glucose production by the liver contributes to hyperglycemia in type II diabetes. Glucose-6-phosphatase (Glc6Pase) is the key enzyme of gluconeogenesis in both the liver and intestine. Here we specify the cAMP/protein kinase A regulation of the Glc6Pase gene in the intestine compared with the liver. Similarly to the liver, the molecular mechanism of cAMP/protein kinase A regulation involves cAMP-response element-binding protein, HNF4 alpha, CAAT/enhancer-binding protein, and HNF1. In contrast to the situation in the liver, we find that different isoforms of CAAT/enhancer-binding protein and HNF1 contribute to the specific regulation of the Glc6Pase gene in the intestine. Moreover, we show that cAMP-response element binding modulator specifically contributes to the regulation of the Glc6Pase gene in the intestine but not in the liver. These results allow us to identify intestine-specific regulators of the Glc6Pase gene and to improve the understanding of the differences in the regulation of gluconeogenesis in the intestine compared with the liver.