Iynedjian P B, Marie S, Gjinovci A, Genin B, Deng S P, Buhler L, Morel P, Mentha G
Division of Clinical Biochemistry and Diabetes Research, University of Geneva School of Medicine, Switzerland.
J Clin Invest. 1995 May;95(5):1966-73. doi: 10.1172/JCI117880.
Glucokinase and phosphoenolpyruvate carboxykinase are key enzymes of glucose metabolism in the rat liver. The former is considered to be instrumental in regulating glucose hepatic release/uptake according to the glycaemia level, and cytosolic phosphoenolpyruvate carboxykinase is a major flux-generating enzyme for gluconeogenesis. The level of expression of both enzymes and the regulation of their mRNAs in the human liver cell were investigated. Surgical biopsies of liver from patients undergoing partial hepatectomies and parenchymal hepatocytes derived from the biopsies were used to assay glucokinase, hexokinase and phosphoenolpyruvate carboxykinase activities. Hepatocytes were placed in culture and the actions of insulin, glucagon and cAMP on glucokinase and phosphoenolpyruvate carboxykinase mRNAs were studied. The main results are: (a) glucokinase accounts for 95% of the glucose phosphorylation activity of human hepatocytes, although this fact is masked in assays of total liver tissue; (b) glucokinase activity is set at a lower level in human hepatocytes than in rat hepatocytes, and vice-versa for the gluconeogenic enzyme phosphoenolpyruvate carboxykinase; and (c) as previously shown in rat liver, glucokinase and phosphoenolpyruvate carboxykinase mRNAs are regulated in a reciprocal fashion in human hepatocytes, insulin inducing the first enzyme and repressing the latter, whereas glucagon has opposite effects. These data have interesting implications with respect to metabolic regulation and intracellular hormone signaling in the human liver.
葡萄糖激酶和磷酸烯醇式丙酮酸羧激酶是大鼠肝脏葡萄糖代谢的关键酶。前者被认为有助于根据血糖水平调节肝脏葡萄糖的释放/摄取，而胞质磷酸烯醇式丙酮酸羧激酶是糖异生的主要通量生成酶。研究了这两种酶在人肝细胞中的表达水平及其mRNA的调控。对接受部分肝切除术患者的肝脏进行手术活检，并将活检获得的实质肝细胞用于检测葡萄糖激酶、己糖激酶和磷酸烯醇式丙酮酸羧激酶的活性。将肝细胞置于培养中，研究胰岛素、胰高血糖素和cAMP对葡萄糖激酶和磷酸烯醇式丙酮酸羧激酶mRNA的作用。主要结果如下：(a)葡萄糖激酶占人肝细胞葡萄糖磷酸化活性的95%，尽管这一事实在全肝组织检测中被掩盖；(b)人肝细胞中葡萄糖激酶活性设定在低于大鼠肝细胞的水平，而糖异生酶磷酸烯醇式丙酮酸羧激酶则相反；(c)如先前在大鼠肝脏中所示，葡萄糖激酶和磷酸烯醇式丙酮酸羧激酶mRNA在人肝细胞中以相反的方式受到调控，胰岛素诱导第一种酶并抑制第二种酶，而胰高血糖素则具有相反的作用。这些数据对人类肝脏的代谢调节和细胞内激素信号传导具有有趣的启示。
