Lactate metabolism in perfused rat lung.

Abstract

Glucose utilization and lactate metabolism were studied in isolated rat lungs perfused with a Krebs-Henseleit bicarbonate buffer, pH 7.4, containing either [U-14C]lactate, [U-14C]glucose, or [U-14C]alanine. Glucose uptake showed an apparent Km of 4.7 mM and a Vmax of 107 mumol-g dry wt-1-h-1. Lactate production under these conditions showed a Vmax of 82.9 mumol-g dry wt-1-h-1. At high circulating lactate level (7 mM), the perfused lung showed an increased capacity to utilize [U-14C]lactate with preferential incorporation into lung lipids. At equal molar concentration (5 mM) [U-14C]lactate was preferentially incorporated over [U-14C]glucose. Addition of 5 mM lactate to the perfusion medium did not affect lactate production. Perfused lungs from fasted rats showed higher lactate production, with increased amounts of [U-14C]alanine converted to lactate by the perfused lung, indicating lactate can also be derived from noncarbohydrate sources. These data show that under aerobic conditions the perfused lung can produce and utilize lactate simultaneously, and lactate can serve as a potential substrate for lung lipids.

Late Gestation Alterations in Fetal Pulmonary Lactate Metabolism in Vivo

“…Inasmuch as glucose levels are normally low in the ovine fetus, it is interesting to note that the in vitro studies in agreement with our findings (14,15) were carried out at relatively lower glucose concentrations [ l o 1 -108 mg/dL (5.6-6.0 mM)] compared to glucose levels in the discordant studies [126-180 mg/dL (7-10 mM)] (1 3, 16). Furthermore, the isolated lungs perfused with 180 mg/dL (10 mM) glucose had higher baseline rates of lactate production 1630 pg/h/g (7.0 pmol/h/g)] (1 6) than did lungs perfused with 10 1 -108 mg/dL glucose [441-468 pg of lactatejhjg (4.9-5.2 pmol/h/g)] (14,15). At lower glucose levels, lactate production may already be decreased and unresponsive to further modulation by lactate.…”

“…Experiments in fresh isolated perfused adult rat lungs have demonstrated no effect of added lactate on the rate of lung lactate production, over perfusate lactate concentrations of 0-45 mg/dL (0-5 mM) (14,15). However, other studies done on isolated perfused adult rat lungs, have reported that lactate in perfusate concentrations of 18 mg/dL (2 mM) decreases lactate production by 95% (16).…”

“…Near term, fetal rat, type I1 pneumocytes in short-term culture and perfused lungs from adult rats have been shown to produce lactate from glucose (13,15). Experiments in fresh isolated perfused adult rat lungs have demonstrated no effect of added lactate on the rate of lung lactate production, over perfusate lactate concentrations of 0-45 mg/dL (0-5 mM) (14,15).…”

“…We speculate that the reduction in lung lactate output noted may reflect the diversion of the end products of glycolysis into surfactant lipid production. Rapid incorporation of labeled lactate into lung phospholipids has been found in isolated adult rat lungs (15). Alternative routes for glucose metabolism, which may also become more active, include the citric acid cycle and the pentosephosphate shunt pathway (1 8).…”

Lactate as substrate for mitochondrial respiration in alveolar epithelial type II cells

“…In these studies, glucose and lactate showed reciprocal inhibition, indi-cating similar pathways of metabolism. The observation that labeled lactate in pulmonary circulation is incorporated into lung lipids in both adult (31) and perinatal (28) lung further implicates ATII cells as a site of lactate consumption in the lung, since ATII cells synthesize the majority of lipid components in pulmonary surfactant. Despite this, lactate consumption has not been directly linked to cellular energetics in ATII cells.…”