Halperin M L, Goguen J M, Chen C B
Renal Division, St. Michael's Hospital, University of Toronto, Ont., Canada.
Can J Physiol Pharmacol. 1992 Nov;70(11):1437-41. doi: 10.1139/y92-203.
The purpose of this study was to explore the interrelations among energy turnover, the selection of fuels, and the production of ammonium (NH4+) in the kidney during chronic metabolic acidosis. Experiments were carried out in dogs because of the extensive background literature in this species. The specific question addressed was, will a diminished rate of oxidation of fatty acids in the kidney permit the rate of extraction of glutamine and the production of NH4+ to rise? Chronic metabolic acidosis was induced by the ingestion of NH4Cl for 5 days to stimulate the rate of production of NH4+. Insulin was administered to diminish the delivery of fatty acids to the kidney. The concentration of fatty acids in plasma fell from 350 +/- 104 to 188 +/- 45 microM, yet there was no significant increase in the rates of production of NH4+, consumption of oxygen, or extraction of glutamine after insulin. Notwithstanding, there was a significant rise in the rate of extraction of lactate by the kidney when expressed per 100-mL glomerular filtration rate. Because there was a significant decline in the level of glutamine in plasma (512 +/- 76 to 359 +/- 42 microM) 1 h after giving insulin, a second series of experiments was carried out. When glutamine was infused after the insulin period, there was no longer a fall in the concentration of this metabolite. Notwithstanding, the rates of extraction of glutamine and production of NH4+ were not higher in the presence of insulin. These data suggest that the rate of oxidation of fatty acids did not limit the rate of oxidation of glutamine in the kidneys of fed dogs with chronic metabolic acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究的目的是探讨慢性代谢性酸中毒期间能量代谢、燃料选择以及肾脏中铵(NH4+)生成之间的相互关系。由于该物种有大量的背景文献,实验在狗身上进行。所解决的具体问题是,肾脏中脂肪酸氧化速率的降低是否会使谷氨酰胺的提取速率和NH4+的生成速率增加?通过摄入NH4Cl 5天来诱导慢性代谢性酸中毒,以刺激NH4+的生成速率。给予胰岛素以减少脂肪酸向肾脏的输送。血浆中脂肪酸浓度从350±104微摩尔降至188±45微摩尔,但胰岛素给药后NH4+生成速率、耗氧率或谷氨酰胺提取率均无显著增加。尽管如此,以每100毫升肾小球滤过率表示时,肾脏对乳酸的提取速率显著增加。由于给予胰岛素1小时后血浆中谷氨酰胺水平显著下降(从512±76微摩尔降至359±42微摩尔),因此进行了第二系列实验。在胰岛素作用期后输注谷氨酰胺时,该代谢物的浓度不再下降。尽管如此,在有胰岛素存在的情况下,谷氨酰胺的提取速率和NH4+的生成速率并未更高。这些数据表明,在患有慢性代谢性酸中毒的喂食狗的肾脏中,脂肪酸氧化速率并未限制谷氨酰胺的氧化速率。(摘要截断于250字)