Endotoxin-induced alterations in hepatic glucose-6-phosphatase activity and gene expression
Endotoxin-induced alterations in hepatic glucose-6-phosphatase activity and gene expression
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DOI：
10.1023/a:1006970229704
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发表时间：
1999-06-01
影响因子：
4.3
通讯作者：
Henry, MC
中科院分区：
文献类型：
--
作者：
Maitra, SR;Gestring, ML;Henry, MC
与内毒素休克相关的血糖变化的机制尚未完全了解，但已知涉及肝脏产生葡萄糖的能力。本研究旨在探讨内毒素（LPS）是否影响葡萄糖-6-磷酸酶（Glu-6-phosphatase，Glu-6-P）在高血糖早期和低血糖后期的表达和活性。给大鼠注射相对大剂量的LPS（20 mg/kg）或生理盐水（对照），并在注射后1或5 h处死。血浆葡萄糖浓度和葡萄糖产生在LPS后1小时升高（2倍），并且在注射后5小时降低（50%）。与时间匹配的对照值相比，肝脏葡萄糖-6-磷酸和果糖-6-磷酸水平在1小时和5小时均显著降低。注射LPS后1 h，肝脏Glu-6-Glu活性和mRNA水平中度升高。5 h时，Glu-6-Pase mRNA丰度下降88%，与该酶活性下降30%相关。血浆胰岛素浓度在LPS后1小时没有不同，并且在5小时从对照值升高2倍。循环中胰高血糖素和皮质酮水平在LPS后的两个时间点均升高。我们的数据表明，LPS诱导的低血糖症和肝葡萄糖产生的减少伴随着Glu-6-β活性和基因表达的抑制。
The mechanisms responsible for the glycemic changes associated with endotoxic shock are not fully understood, but are known to involve the ability of the liver to produce glucose. The purpose of the present study was to determine whether endotoxin (LPS) influences the expression and activity of glucose-6-phosphatase (Glu-6-Pase) during the early hyperglycemic phase and the later hypoglycemic phase. Rats were injected with a relatively large dose of LPS (20 mg/kg) or saline (control), and sacrificed at 1 or 5 h post-injection. Both the plasma glucose concentration and glucose production were elevated 1 h post-LPS (2-fold) and both decreased at 5 h postinjection (50%). Compared to time-matched control values, hepatic glucose-6-phosphate and fructose-6-phosphate levels were significantly decreased at both 1 and 5 h. Hepatic Glu-6-Pase activity and mRNA levels were moderately increased, 1 h after injection of LPS. At 5 h, an 88% decrease in mRNA abundance for Glu-6-Pase was associated with a 30% decrease in activity of this enzyme. Plasma insulin concentrations were not different 1 h after LPS and were elevated 2-fold from control values at 5 h. Circulating levels of glucagon and corticosterone were elevated at both time points following LPS. Our data indicate that the LPS-induced hypoglycemia and reduction in hepatic glucose production were accompanied by a depression in Glu-6-Pase activity and gene expression.