Induction of IGF-I production by amino acids in the liver : Its significance in the cirrhotic liver

胰岛素样生长因子I(IGF-I)在各种类型细胞的生长、代谢、生存和氧化应激中起着重要作用。IGF-I主要由肝脏产生，尤其是肝细胞。肝硬变患者血清IGF-I水平降低。补充IGF-I可改善肝硬变患者的肝功能。本研究通过检测氨基酸对肝细胞产生IGF-I的刺激作用，以及IGF-I对肝细胞生长和功能的影响，探讨氨基酸对肝硬变患者肝功能改善的可能性。在多种氨基酸中，支链氨基酸尤其是亮氨酸能促进大鼠原代培养肝细胞产生IGF-I。加入IGF-I可促进大鼠肝细胞增殖、蛋白质合成和葡萄糖代谢。在这些细胞中，mTOR依赖的信号通路上调。加入mTOR途径的阻断剂可消除IGF-I的刺激作用。这些观察结果表明，IGF-I直接刺激肝细胞功能，刺激IGF-I的产生可能是肝硬变患者的一种治疗方案。

Insulin-like growth factor I (IGF-I) plays an important role in growth, metabolism, survival and oxidative stress of various types of cells. IGF-I is produced predominantly by the liver, especially by hepatocytes. Serum IGF-I levels are decreased in patients with liver cirrhosis. Supplementation of IGF-I induces the improvement of liver function in patients with liver cirrhosis. In this study, we examined stimulatory effect of amino acids on IGF-I production by hepatocytes, and the effect of IGF-I on hepatocyte growth and function to investigate the possibility that amino acid administration improves liver function in patients with liver cirrhosis.Among various amino acids, branched-chain amino acids, especially leucine, increased IGF-I production by rat primary cultured hepatocytes. Addition of IGF-I stimulated proliferation, protein production and glucose metabolism by rat hepatocytes. In these cells, mTOR dependent signaling pathway was up-regulated. The stimulatory effect of IGF-I was abrogated by the addition of an inhibitor of mTOR pathway. These observations suggest that IGF-I stimulates hepatocyte function directly, and stimulation of IGF-I production is a possible therapeutic candidate in patients with liver cirrhosis.