Effects of Glycine on Hepatic IGF-I Expression Regulation and the Underlying Signaling Pathways
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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 receptor pathway (JAK2/STAT5) and muscular IGF-I receptor pathway (ERK/Akt/mTOR) were also detected by western 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.
