Acute alterations in growth hormone insulin-like growth factor axis in humans injected with endotoxin
Acute alterations in growth hormone insulin-like growth factor axis in humans injected with endotoxin
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DOI：
10.1152/ajpregu.1997.273.1.r371
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发表时间：
1997-07-01
影响因子：
2.8
通讯作者：
Prough, DS
中科院分区：
文献类型：
--
作者：
Lang, CH;Pollard, V;Prough, DS
本研究的目的是研究内毒素(脂多糖)对人胰岛素样生长因子(IGF)系统的急性影响。健康成人静脉注射大肠杆菌脂多糖(4 ng/kg)，连续5h采集血样；注射生理盐水作为时间匹配对照。在实验的最后2小时内，可提取的IGF-I浓度逐渐下降，降幅接近20%；游离IGF-I水平无明显变化。此外，脂多糖还可显著提高生长激素(GH)浓度，但这种升高是短暂的。内毒素注射后2小时，胰岛素样生长因子结合蛋白(BP)-1水平升高5倍以上，此后逐渐恢复到基线水平。注射内毒素后，IGFBP-2浓度也升高，但最大升幅(接近基础水平的50%)出现在方案的最后2小时。相反，IGFBP-3水平在检测的内毒素反应期间没有变化，BP-3蛋白降解片段的数量也没有明显增加。皮质醇水平早期升高，并在整个方案中保持为基线水平的两到三倍。血糖和胰岛素的血清浓度没有明显变化。脂多糖还可使肿瘤坏死因子早期升高，随后产生白细胞介素6的升高。这些数据表明，人类对脂多糖的GH-IGF轴的急性变化与在其他创伤条件下观察到的人类以及内毒素血症和感染的动物模型中观察到的变化相似。
The purpose of the present study was to characterize the acute changes in the insulin-like growth factor (IGF) system in humans after administration of endotoxin (lipopolysaccharide; LPS). Escherichia coli LPS (4 ng/kg) was injected intravenously into healthy adults, and serial blood samples were collected for the next 5 h; subjects injected with saline served as time-matched controls. LPS administration resulted in a gradual decrease in the total extractable IGF-I concentration, which was reduced by similar to 20% over the final 2 h of the experiment; levels of free IGF-I were not significantly altered. LPS also produced a marked but transient elevation in growth hormone (GH) concentration. IGF-binding protein (BP)-1 levels were elevated more than fivefold 2 h after LPS injection, and thereafter levels gradually returned toward baseline. IGFBP-2 concentration also increased after LPS injection, but the maximal increase (similar to 50% above basal) was observed during the final 2 h of the protocol. In contrast, IGFBP-3 levels did not vary over the period examined in response to LPS, and there was no apparent increase in number of BP-3 proteolytic fragments. Cortisol levels were increased early and remained two- to threefold above baseline throughout the protocol. No significant alterations in serum concentration of glucose or insulin were noted. LPS also produced an early elevation in tumor necrosis factor and a later increase in interleukin-6. These data indicate that the acute changes in the GH-IGF axis in humans in response to LPS are comparable with those observed in humans in other traumatic conditions and in animal models of endotoxemia and infection.