LACTATE METABOLISM IN ISOLATED PERFUSED RAT-KIDNEY - RELATIONS TO RENAL-FUNCTION AND GLUCONEOGENESIS

LACTATE METABOLISM IN ISOLATED PERFUSED RAT-KIDNEY - RELATIONS TO RENAL-FUNCTION AND GLUCONEOGENESIS
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DOI:
10.1113/jphysiol.1976.sp011286
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发表时间:
1976-01-01
影响因子:
5.5
通讯作者:
LITTLE, JR
LITTLE, JR
中科院分区:
医学1区
文献类型:
--
作者:
COHEN, JJ;LITTLE, JR

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在完整犬中,由于输尿管压力升高导致的肾小球滤过率和肾净钠重吸收的降低与肾乳酸氧化率的降低无关,尽管肾总二氧化碳的产生与肾净重吸收钠和肾小球滤过率的变化成正比。为了确定在没有其他添加底物的情况下,乳酸代谢是仅支持基础肾代谢,还是也能增强肾功能,我们量化了离体灌流大鼠肾脏的乳酸利用率和脱羧率与肾功能和肾脏基础代谢的一项指标--葡萄糖产生的关系。灌流液为Krebs-Ringer碳酸氢盐(pH 7.35~7.48),加入组份V牛血清白蛋白6g/100ml,加入L-(+)-乳酸,使乳酸浓度由内源性升高至2.5、5.0或10 mM。测定了乳酸净利用率、乳酸脱羧率(由L-(+)-[U-14C]乳酸产生~(14)CO_2)、净葡萄糖生成率和Na~+净重吸收率。乳酸氧化的表观Km和Vmax分别为2.1 mm和1.29微克分子.G-1.cntdo.Min-1。总乳酸盐利用率没有明显的最大值,这是因为葡萄糖产生速率随着乳酸盐浓度的增加而持续增加。当乳酸盐浓度约为10 mM时,葡萄糖产量约占所利用乳酸盐总量的一半。因此,肾脏的基本能量需求不必是恒定的,因为葡萄糖的产生随着乳酸浓度的增加而增加。乳酸氧化率和乳酸利用率与肾小管对Na+的净重吸收、滤过的Na+重吸收百分率和肾小球滤过率均显著相关。肾脏对Na+的净吸收的主要部分可能是由结合到白蛋白或来自肾组织的底物的代谢支持的,因为过滤后的Na+重吸收的百分比从不添加乳酸时的约78%增加到初始乳酸浓度为10 mM时的97%。添加乳酸可提高基础代谢和肾小管功能。无论是乳酸的存在,还是通过氧化或其他途径利用乳酸,都没有确定是否增加了肾脏对Na+的净吸收和肾小球滤过率。
In the intact dog decreases in both glomerular filtration rate and net renal Na+ reabsorption due to raised ureteral pressure were not associated with a decrease in renal lactate oxidation rate, although total renal CO2 production decreased in proportion to the changes in net renal reabsorption of Na+ and glomerular filtration rate. In order to determine whether in the absence of other added substrates the metabolism of lactate supports only the basal renal metabolism or can enhance renal function as well, the rate of lactate utilization and decarboxylation by the isolated perfused rat kidney were quantified in relation to renal function and 1 measure of renal basal metabolism, glucose production. The perfusate was Krebs-Ringer bicarbonate (pH 7.35-7.48) with Fraction V bovine serum albumin, 6g/100 ml. L-(+)-lactate was added to raise the lactate concentration from endogenous levels to 2.5, 5.0 or 10 mM. The following were determined: net lactate utilization rate, lactate decarboxylation rate (14CO2 produced from L-(+)-[U-14C]lactate), net glucose production rate, and net re-absorptive rate of Na+. The apparent Km and Vmax for lactate oxidation were 2.1 mM and 1.29 .mu.mole .cntdot. g-1 .cntdot. min-1, respectively. There was no apparent maximum for total lactate utilization rate due to continuing increases in glucose production rate as lactate concentration was raised. At approximately 10 mM lactate, glucose production accounted for about half of the total lactate utilized. Therefore the basal energy requirements of the kidney need not be constant, since glucose production increases as lactate concentration is raised. Both lactate oxidation rate and lactate utilization rate were significantly correlated with the net reabsorption of Na+ by the renal tubules, with the percentage of filtered Na+ reabsorbed and with the glomerular filtration rate. The major fraction of the net renal reabsorption of Na+ was probably supported by the metabolism of substrates either bound to albumin or derived from renal tissue since the percentage of filtered Na+ reabsorbed increased from approximately 78%, when no lactate was added, to 97% when initial lactate concentration was 10 mM. Addition of lactate increased both the basal metabolism and tubular function. Whether it was the presence of lactate, or its utilization by oxidative or by other pathways which enhanced net renal reabsorption of Na+ and the glomerular filtration rate was not determined.