Krause Ulrike, Bertrand Luc, Maisin Liliane, Rosa Maria, Hue Louis
Hormone and Metabolic Research Unit, Christian de Duve International Institute of Cellular and Molecular Pathology, and University of Louvain Medical School, Brussels, Belgium.
Eur J Biochem. 2002 Aug;269(15):3742-50. doi: 10.1046/j.1432-1033.2002.03069.x.
Liver metabolism is influenced by hormones and nutrients. Amino acids such as glutamine or leucine induce an anabolic response, which resembles that of insulin in muscle and adipose tissue. In this work, the signalling pathways and the effects of insulin were compared to those of glutamine and leucine in isolated hepatocytes from normal and streptozotocin-diabetic rats. Glutamine increased cell volume and induced an anabolic response characterized by an activation of acetyl-CoA carboxylase (ACC), glycogen synthase (GS) and p70 ribosomal S6 kinase (p70S6K), the key enzymes in fatty acid, glycogen and protein synthesis, respectively. The effects of glutamine were independent of insulin and did not share its signalling components. Leucine, which is poorly metabolized by the liver and does not modify cell volume, activated ACC and p70S6K, and exerted a synergistic effect on the glutamine-induced activation of ACC and p70S6K. These amino acids did not affect insulin signalling. Insulin alone had no anabolic effect in hepatocytes, despite the activation of protein kinase B. Nevertheless, it enhanced the activation of ACC and p70S6K induced by leucine. However, insulin injected intravenously activated rat liver p70S6K. In hepatocytes from streptozotocin-diabetic animals, the metabolic responses to the amino acids and insulin were similar to those in normal hepatocytes. We conclude that glutamine, insulin and leucine exert different effects that are mediated by different signalling pathways, although their effects are combinatory. The anabolic effect of insulin in hepatocytes was strictly dependent on the permissive action of leucine.
肝脏代谢受激素和营养物质的影响。谷氨酰胺或亮氨酸等氨基酸可诱导合成代谢反应，这类似于胰岛素在肌肉和脂肪组织中的作用。在本研究中，将胰岛素与谷氨酰胺和亮氨酸在正常大鼠和链脲佐菌素诱导的糖尿病大鼠分离的肝细胞中的信号通路及作用进行了比较。谷氨酰胺增加细胞体积，并诱导以乙酰辅酶A羧化酶（ACC）、糖原合酶（GS）和p70核糖体S6激酶（p70S6K）激活为特征的合成代谢反应，这三种酶分别是脂肪酸、糖原和蛋白质合成中的关键酶。谷氨酰胺的作用不依赖于胰岛素，且不共享其信号成分。亮氨酸在肝脏中代谢较差且不改变细胞体积，它激活ACC和p70S6K，并对谷氨酰胺诱导的ACC和p70S6K激活发挥协同作用。这些氨基酸不影响胰岛素信号传导。尽管蛋白激酶B被激活，但单独的胰岛素在肝细胞中没有合成代谢作用。然而，它增强了亮氨酸诱导的ACC和p70S6K的激活。然而，静脉注射胰岛素可激活大鼠肝脏中的p70S6K。在链脲佐菌素诱导的糖尿病动物的肝细胞中，对氨基酸和胰岛素的代谢反应与正常肝细胞中的相似。我们得出结论，谷氨酰胺、胰岛素和亮氨酸发挥不同的作用，由不同的信号通路介导，尽管它们的作用具有组合性。胰岛素在肝细胞中的合成代谢作用严格依赖于亮氨酸的允许作用。
