甘氨酸调控肝脏IGF-1的表达及信号通路

Effects of Glycine on Hepatic IGF-I Expression Regulation and the Underlying Signaling Pathways

为研究甘氨酸(Glycine,Gly)对肝脏IGF-1表达和分泌的影响,本文一方面采用不同浓度Gly离体处理HepG2肝细胞,另一方面采用小鼠尾静脉注射1.0 g/kg Gly和等摩尔Ala,0.5 h和1 h后采集血液、肝脏和肌肉样品。研究采用定量PCR检测了IGF-1以及IGFBPs基因表达水平的影响,同时运用Western blot法分析了肝细胞和肝脏生长激素受体通路(JAK2/STAT5)与肌肉IGF-I受体通路(ERK/Akt/m TOR)的变化。研究结果发现,不同浓度的Gly能剂量依赖性提高HepG2细胞IGF-1的蛋白和m RNA表达水平;1.0 g/kg Gly能显著提高小鼠血清中的IGF-1和白蛋白含量,且极显著提高肝脏IGF-1和IGFBP-3 m RNA水平,下调IGFBP-1 m RNA水平。细胞和活体试验均表明,Gly能够有效激活肝细胞和肝脏JAK2/STAT5信号通路,同时提高腓肠肌IGF-I受体信号通路磷酸化水平。这些研究说明甘氨酸可能直接提高肝脏生长激素受体信号通路敏感性,从而促进IGF-1的表达和分泌。研究结果为深入揭示甘氨酸的分子营养学功能和作用机制提供了实验依据。

To investigate the effects of Glycine（Gly） on the expression and secretion of hepatic insulin-like growth factor 1（IGF-1）, HepG2 cells were treated with different concentrations of Gly in vitro. Meanwhile, mice were injected（i.v.） with 1.0 g/kg Gly or equimolar alanine（Ala） via tail veins, and blood, liver, and gastrocnemius samples were collected at 0.5 h and 1 h post-injection. The expression of IGF-1 and insulin-like growth factor binding proteins（IGFBPs） m RNAs in hepatocytes and mouse liver was analyzed by quantitative polymerase chain reaction（q PCR）. Meanwhile, changes in the hepatic growth hormone receptor pathway（JAK2/STAT5） and muscular IGF-I receptor pathway（ERK/Akt/m TOR） were also detected by western blot. The results showed that the expression levels of IGF-1 protein and m RNA in HepG2 cells were elevated by Gly in a dose-dependent manner. The in vivo data demonstrated that 1.0 g/kg Gly could remarkably increase the serum IGF-1 and albumin levels, significantly upregulate the expression levels of hepatic IGF-1 and IGFBP-3 m RNA, and downregulate that of IGFBP-1 m RNA. In vitro and in vivo experiments both indicated that Gly could effectively activate the JAK2/STAT5 signaling pathway in HepG2 cells and mouse liver, and enhance the phosphorylation level of the IGF-I receptor signaling pathway in gastrocnemius. These results suggest that glycine may directly improve the sensitivity of hepatic growth hormone receptor signaling pathways, thus promoting the expression and secretion of IGF-1. These results provide the experimental basis for revealing the molecular nutrition function and action mechanism of Gly.