Lupo M A, Cefalu W T, Pardridge W M
Department of Medicine, UCLA School of Medicine 90024.
Metabolism. 1990 Apr;39(4):374-7. doi: 10.1016/0026-0495(90)90251-7.
Lactate clearance by liver plays an important role in lactate homeostasis and in the development of lactic acidosis. The role of lactate delivery to liver as a limiting factor in hepatic uptake of lactate is unclear. Lactate delivery of mechanisms could be important if rates of lactate transport approximate rates of lactate metabolism by liver. The rates of lactate transport into liver have been determined in vitro with isolated liver cells and the results have been conflicting. Therefore, the present studies measure the rate of transport of [14C]-L-lactate, and its poorly metabolizeable stereoisomer, [14C]-D-lactate, into rat liver in vivo using a portal vein injection technique. The transport of [3H]-water and of [14C]-sucrose, an extracellular reference compound, were also studied. Portal blood flow was determined from the kinetics of [3H]-water efflux in liver and was 1.93 +/- 0.22 mL/min/g. The volumes of distribution of [14C]-L-lactate, and [14C]-sucrose were 1.31 +/- 0.22, 0.71 +/- 0.07, and 0.22 +/- 0.07 mL/g, respectively. The extraction of unidirectional influx of [14C]-L-lactate and [14C]-D-lactate by rat liver was 93% +/- 10% and 91% +/- 9%, respectively. The rate of lactate transport into rat liver in vivo, 1.8 mumols.min-1.g-1, is approximately twofold greater than the rate of lactate metabolism by rat liver reported in the literature. Therefore, lactate uptake by liver may not be limited by transport under normal conditions. However, conditions such as decreased portal blood flow, which slow lactate delivery to liver by 50% or more, could cause lactate uptake by liver to be limited by transport of circulating lactate.
肝脏对乳酸的清除在乳酸稳态及乳酸性酸中毒的发展过程中起着重要作用。乳酸输送至肝脏作为肝脏摄取乳酸的一个限制因素,其作用尚不清楚。如果乳酸转运速率接近肝脏乳酸代谢速率,那么乳酸输送机制可能很重要。已利用分离的肝细胞在体外测定了乳酸转运至肝脏的速率,结果存在矛盾。因此,本研究采用门静脉注射技术在体内测量了[14C]-L-乳酸及其代谢能力较差的立体异构体[14C]-D-乳酸转运至大鼠肝脏的速率。还研究了[3H]-水和细胞外参考化合物[14C]-蔗糖的转运情况。根据肝脏中[3H]-水流出的动力学测定门静脉血流量,为1.93±0.22 mL/min/g。[14C]-L-乳酸、[14C]-蔗糖的分布容积分别为1.31±0.22、0.71±0.07和0.22±0.07 mL/g。大鼠肝脏对[14C]-L-乳酸和[14C]-D-乳酸单向流入的摄取率分别为93%±10%和91%±9%。体内[14C]-L-乳酸转运至大鼠肝脏的速率为1.8 μmol·min-1·g-1,约为文献报道的大鼠肝脏乳酸代谢速率的两倍。因此,在正常情况下,肝脏对乳酸的摄取可能不受转运限制。然而,诸如门静脉血流量减少等情况,会使乳酸输送至肝脏的速度减慢50%或更多,这可能导致肝脏对乳酸的摄取受到循环乳酸转运的限制。