Hill M, McCallum R
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
J Clin Invest. 1991 Sep;88(3):811-6. doi: 10.1172/JCI115381.
The molecular mechanism involved in altered regulation of the rate-limiting enzyme in hepatic gluconeogenesis, phosphoenolpyruvate carboxykinase (PEPCK), during endotoxemia is not completely understood. We examined, therefore, the effect of a nonlethal dose of Escherichia coli endotoxin on PEPCK gene expression in fasted rats. 5 h after endotoxin treatment, the PEPCK transcription rate and the amount of mRNA(PEPCK) were significantly decreased at a time when the insulin/glucagon (I/G) molar ratio and plasma corticosterone levels were significantly increased. Similar results were observed in a time course study, in which altered cAMP induction of PEPCK gene expression paralleled changes in the I/G molar ratio. In diabetic rats treated with endotoxin, PEPCK gene expression was decreased in the absence, however, of an increased I/G molar ratio. This finding indicates that other factors, such as inflammatory mediators or cytokines, alter PEPCK gene transcription during endotoxemia. IL-6, a putative mediator of endotoxin action in the liver, had no effect on PEPCK gene expression in fasted rats, but did decrease cAMP induction of PEPCK gene expression. These results indicate that, during endotoxemia, regulation of PEPCK gene expression is influenced by inflammatory mediators in addition to the classical endocrine hormones. IL-6, however, does not appear to be involved directly in the altered regulation of the PEPCK gene during endotoxemia.
内毒素血症期间，肝脏糖异生限速酶磷酸烯醇丙酮酸羧激酶（PEPCK）调节改变所涉及的分子机制尚未完全明确。因此，我们研究了非致死剂量的大肠杆菌内毒素对禁食大鼠PEPCK基因表达的影响。内毒素处理5小时后，当胰岛素/胰高血糖素（I/G）摩尔比和血浆皮质酮水平显著升高时，PEPCK转录速率和mRNA（PEPCK）量显著降低。在一项时间进程研究中观察到了类似结果，其中PEPCK基因表达的cAMP诱导变化与I/G摩尔比的变化平行。在内毒素处理的糖尿病大鼠中，PEPCK基因表达降低，但I/G摩尔比并未升高。这一发现表明，在内毒素血症期间，其他因素，如炎症介质或细胞因子，会改变PEPCK基因转录。IL-6是肝脏中内毒素作用的一种假定介质，对禁食大鼠的PEPCK基因表达没有影响，但确实降低了PEPCK基因表达的cAMP诱导。这些结果表明，在内毒素血症期间，除了经典的内分泌激素外，炎症介质也会影响PEPCK基因表达的调节。然而，IL-6似乎并未直接参与内毒素血症期间PEPCK基因调节的改变。
