Role of hepatic STAT3 in brain-insulin action on hepatic glucose production
Role of hepatic STAT3 in brain-insulin action on hepatic glucose production
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DOI：
10.1016/j.cmet.2006.02.009
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发表时间：
2006-04-01
期刊：
影响因子：
29
通讯作者：
Kasuga, M
中科院分区：
文献类型：
--
作者：
Inoue, H;Ogawa, W;Kasuga, M
STAT 3通过抑制肝脏中致炎基因的表达来调节葡萄糖稳态。然而，肝脏STAT 3受营养或激素状态调节的机制仍然未知。在这里，我们表明，无论是通过葡萄糖给药或静脉注射胰岛素实现的血浆胰岛素浓度的增加，刺激肝脏中的STAT 3的酪氨酸磷酸化。胰岛素的这种作用是由激素在脑中的作用介导的，并且由脑胰岛素作用诱导的肝IL-6的增加对于STAT 3的激活是必需的。在肝脏特异性STAT 3缺乏或IL-6缺乏的小鼠中，脑室内胰岛素输注诱导的肝葡萄糖产生和致炎基因表达的抑制作用受损。因此，这些结果表明，肝脏中的IL-6-STAT 3信号传导有助于大脑中的胰岛素作用，导致肝脏葡萄糖产生的抑制。
STAT3 regulates glucose homeostasis by suppressing the expression of gluconeogenic genes in the liver. The mechanism by which hepatic STAT3 is regulated by nutritional or hormonal status has remained unknown, however. Here, we show that an increase in the plasma insulin concentration, achieved either by glucose administration or by intravenous insulin infusion, stimulates tyrosine phosphorylation of STAT3 in the liver. This effect of insulin was mediated by the hormone's effects in the brain, and the increase in hepatic IL-6 induced by the brain-insulin action is essential for the activation of STAT3. The inhibition of hepatic glucose production and of expression of gluconeogenic genes induced by intracerebral ventricular insulin infusion was impaired in mice with liver-specific STAT3 deficiency or in mice with IL-6 deficiency. These results thus indicate that IL-6-STAT3 signaling in the liver contributes to insulin action in the brain, leading to the suppression of hepatic glucose production.