Ribaux Pascale, Gjinovci Asllan, Sadowski Henry B, Iynedjian Patrick B
Division of Clinical Biochemistry and Experimental Diabetes Research, University of Geneva School of Medicine, Switzerland.
Endocrinology. 2002 Oct;143(10):3766-72. doi: 10.1210/en.2002-220304.
Insulin and GH can activate common signaling elements in many tissues and cell lines. We investigated the possibility of overlap in signaling pathways activated by insulin and GH in a key target cell, the hepatocyte. In primary cultures of rat hepatocytes, GH caused a dose- and time-dependent increase in tyrosine phosphorylation of signal transducer and activator of transcription 5. This was accompanied by the induction of the mRNA encoding suppressor of cytokine signaling 2. Neither of these effects took place in companion hepatocytes challenged with insulin. By contrast, insulin caused a rapid and sustained phosphorylation of protein kinase B, accompanied by a massive induction of the mRNA encoding glucokinase. GH had no detectable effect on phosphorylation of protein kinase B or level of glucokinase mRNA. Insulin also elicited brief hyperphosphorylation of ERK1 and 2, an effect not seen in GH-stimulated hepatocytes. Thus, there was a clear demarcation of signaling events triggered in hepatocytes by insulin and GH, and this was accompanied by hormone-specific responses with respect to the induction of gene expression. Additionally, the current results show that signal transducer and activator of transcription 5 activation is neither necessary nor sufficient for the insulin-dependent induction of hepatic glucokinase.
胰岛素和生长激素（GH）可在许多组织和细胞系中激活共同的信号元件。我们研究了在关键靶细胞——肝细胞中，胰岛素和GH激活的信号通路是否存在重叠。在原代培养的大鼠肝细胞中，GH导致信号转导及转录激活因子5的酪氨酸磷酸化呈剂量和时间依赖性增加。这伴随着细胞因子信号转导抑制因子2编码mRNA的诱导。在用胰岛素刺激的对照肝细胞中，这两种效应均未发生。相比之下，胰岛素导致蛋白激酶B迅速且持续磷酸化，同时伴随着葡萄糖激酶编码mRNA的大量诱导。GH对蛋白激酶B的磷酸化或葡萄糖激酶mRNA水平无明显影响。胰岛素还引发细胞外信号调节激酶1和2的短暂过度磷酸化，这在GH刺激的肝细胞中未观察到。因此，胰岛素和GH在肝细胞中触发的信号事件有明显区分，并且伴随着基因表达诱导方面的激素特异性反应。此外，目前的结果表明，信号转导及转录激活因子5的激活对于胰岛素依赖性诱导肝葡萄糖激酶既非必要条件也非充分条件。
