Munnich A, Besmond C, Darquy S, Reach G, Vaulont S, Dreyfus J C, Kahn A
J Clin Invest. 1985 Mar;75(3):1045-52. doi: 10.1172/JCI111766.
Aldolase B is an enzyme of the glycolytic pathway whose activity and mRNA levels in the liver fluctuate according to dietary status. Both the enzyme activity and the mRNA concentration decline during fasting and increase four- to eightfold upon refeeding of a carbohydrate-rich diet. The mechanism, however, of the mRNA induction remains unknown. To elucidate the mechanisms that regulate this induction responsive to dietary stimuli, we have studied the roles of hormones and glycolytic substrates on aldolase B gene expression in three tissues that synthesize the enzyme. Using a cDNA probe complementary to rat aldolase B mRNA, we determined the amount of cytoplasmic RNAs in the liver, kidney, and small intestine of normal, adrenalectomized, thyroidectomized, diabetic, and glucagon- or cAMP-treated animals refed either a fructose-rich or a maltose-rich diet. The in vivo hormonal control of gene expression was found to be very different in the three organs tested. In the liver, cortisone and thyroid hormones were required for the induction of the specific mRNA by carbohydrates, while in the kidney none of the hormonal modifications tested altered the level of mRNA induction. In the liver, but not in the kidney, diabetes and glucagon administration abolished the induction of aldolase B mRNAs in animals refed the maltose-rich diets. In the small intestine, only diabetes and thyroidectomy affected the gene expression. Finally, no induction occurred when normal fasted rats were given any of the hormones. Thus, the in vivo hormonal control of liver aldolase B gene expression differs significantly from that of kidney and small intestine. In the liver, the mRNA induction requires the presence of dietary carbohydrates, of permissive hormones, and the cessation of glucagon release, while in the kidney, the induction of the mRNAs by fructose occurs regardless of the hormonal status of the animals. The hormonal control of aldolase B mRNA levels in the small intestine is intermediate.
醛缩酶B是糖酵解途径中的一种酶，其在肝脏中的活性和mRNA水平会根据饮食状态而波动。在禁食期间，该酶的活性和mRNA浓度都会下降，而在重新喂食富含碳水化合物的饮食后，二者会增加4至8倍。然而，mRNA诱导的机制仍然未知。为了阐明调节这种对饮食刺激产生反应的诱导机制，我们研究了激素和糖酵解底物在合成该酶的三种组织中对醛缩酶B基因表达的作用。使用与大鼠醛缩酶B mRNA互补的cDNA探针，我们测定了正常、肾上腺切除、甲状腺切除、糖尿病以及用胰高血糖素或cAMP处理的动物在重新喂食富含果糖或富含麦芽糖的饮食后，肝脏、肾脏和小肠中的细胞质RNA量。结果发现，在所测试的三个器官中，基因表达的体内激素控制差异很大。在肝脏中，碳水化合物诱导特异性mRNA需要可的松和甲状腺激素，而在肾脏中，所测试的任何激素改变都不会改变mRNA诱导水平。在肝脏中，而非肾脏中，糖尿病和给予胰高血糖素会消除重新喂食富含麦芽糖饮食的动物中醛缩酶B mRNA的诱导。在小肠中，只有糖尿病和甲状腺切除术会影响基因表达。最后，正常禁食的大鼠给予任何一种激素后都不会发生诱导。因此，肝脏醛缩酶B基因表达的体内激素控制与肾脏和小肠的显著不同。在肝脏中，mRNA诱导需要饮食中的碳水化合物、允许性激素的存在以及胰高血糖素释放的停止，而在肾脏中，果糖对mRNA的诱导与动物的激素状态无关。小肠中醛缩酶B mRNA水平的激素控制处于中间状态。
