Bagby G J, Lang C H, Hargrove D M, Thompson J J, Wilson L A, Spitzer J J
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
Circ Shock. 1988 Feb;24(2):111-21.
This study was conducted to determine if macrophage elaborated monokines in general, and human recombinant tumor necrosis factor (hrTNF alpha) in particular alter glucose metabolism in a manner analogous to that observed in endotoxin-treated animals. Endotoxin-tolerant rats were infused for 3 hr with saline, E. coli endotoxin (100 micrograms/l weight) or monokines contained in conditioned media from endotoxin-stimulated RAW 264.7 cells (1 microgram/ml). Compared to saline- and endotoxin-infused rats, animals receiving the monokine mixture had no change in mean arterial blood pressure or heart rate but exhibited overt signs of morbidity including stupor and diarrhea. Monokine-infused rats remained euglycemic but had elevated lactate concentrations and a 15-30% increase in glucose rate of appearance (Ra). Nontolerant rats received a 3 hr infusion of saline, hrTNF alpha (15 micrograms/100 g), or heat-treated hrTNF alpha. HrTNF alpha infusion increased glucose Ra about 25% compared to the two control groups but did so without producing signs of morbidity seen in the monokine infused animals. Serum TNF levels were 6-fold higher in rats infused with the monokine mixture compared to animals infused with hrTNF alpha, and this reflected the different levels of TNF contained in the monokine mixture and hrTNF alpha infusates. Plasma insulin, glucagon, and catecholamine concentrations were increased in rats infused with either the monokine mixture or hrTNF alpha, but the increases were more pronounced in rats receiving the monokine mixture. The results demonstrate that monokines and hrTNF alpha increase glucose production in vivo, and that the effect may be mediated by endocrine changes known to influence glucose homeostasis.
本研究旨在确定巨噬细胞产生的单核因子，尤其是重组人肿瘤坏死因子（hrTNFα），是否以类似于内毒素处理动物的方式改变葡萄糖代谢。给内毒素耐受的大鼠输注生理盐水、大肠杆菌内毒素（100微克/体重）或内毒素刺激的RAW 264.7细胞条件培养基中的单核因子（1微克/毫升）3小时。与输注生理盐水和内毒素的大鼠相比，接受单核因子混合物的动物平均动脉血压和心率没有变化，但出现了明显的发病迹象，包括昏迷和腹泻。输注单核因子的大鼠血糖保持正常，但乳酸浓度升高，葡萄糖出现率（Ra）增加15%-30%。非耐受大鼠接受3小时的生理盐水、hrTNFα（15微克/100克）或热处理的hrTNFα输注。与两个对照组相比，输注hrTNFα使葡萄糖Ra增加约25%，但未产生输注单核因子动物出现的发病迹象。与输注hrTNFα的动物相比，输注单核因子混合物的大鼠血清TNF水平高6倍，这反映了单核因子混合物和hrTNFα输注液中TNF的不同含量。输注单核因子混合物或hrTNFα的大鼠血浆胰岛素、胰高血糖素和儿茶酚胺浓度均升高，但在接受单核因子混合物的大鼠中升高更为明显。结果表明，单核因子和hrTNFα在体内增加葡萄糖生成，且这种作用可能由已知影响葡萄糖稳态的内分泌变化介导。
