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

XU Jing-ren; LIU Shi-zhong; ZHANG Meng-yuan; WAN Xiao-juan; CAI Xing-cai; WANG Li-na; ZHU Xiao-tong; GAO Ping; WANG Song-bo; JIANG Qing-yan; SHU Gang

doi:10.13982/j.mfst.1673-9078.2017.3.001

Abstract：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) mRNAs in hepatocytes and mouse liver was analyzed by quantitative polymerase chain reaction (qPCR).Meanwhile,changes in the hepatic growth hormone receptorpathway (JAK2/STAT5) and muscular IGF-I receptor pathway (ERK/Akt/mTOR) were also detected by westem blot.The results showed that the expression levels of IGF-1 protein and mRNA 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 mRNA,and downregulate that of IGFBP-1 mRNA.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.