title: Kinetics of lactate transport into rat liver in vivo.
abstract: 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.
authors.affiliation: Department of Medicine, UCLA School of Medicine 90024.
authors.forename: M A
authors.initials: MA
authors.lastname: Lupo
authors.forename: W T
authors.initials: WT
authors.lastname: Cefalu
authors.forename: W M
authors.initials: WM
authors.lastname: Pardridge
mesh_terms: D000818:Animals; D001692:Biological Transport; D001834:Body Water / Q000378:metabolism; D002250:Carbon Radioisotopes; D007700:Kinetics; D007773:Lactates / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation; D008297:Male; D011169:Portal Vein / Q000502:physiology; D011865:Radioisotope Dilution Technique; D051381:Rats; D011919:Rats, Inbred Strains; D013395:Sucrose / Q000378:metabolism; D014316:Tritium
chemical_list: D002250:Carbon Radioisotopes; D007773:Lactates; D014316:Tritium; D013395:Sucrose