To understand the meaning of the lactate threshold (LT) and to test the hypothesis that endurance training augments lactate kinetics [i.e., rates of appearance and disposal (Ra and Rd, respectively, mg·kg(-1)·min(-1)) and metabolic clearance rate (MCR, ml·kg(-1)·min(-1))], we studied six untrained (UT) and six trained (T) subjects during 60-min exercise bouts at power outputs (PO) eliciting the LT. Trained subjects performed two additional exercise bouts at a PO 10% lower (LT-10%), one of which involved a lactate clamp (LC) to match blood lactate concentration ([lactate]b) to that achieved during the LT trial. At LT, lactate Ra was higher in T (24.1 ± 2.7) than in UT (14.6 ± 2.4; P < 0.05) subjects, but Ra was not different between UT and T when relative exercise intensities were matched (UT-LT vs. T-LT-10%, 67% Vo2max). At LT, MCR in T (62.5 ± 5.0) subjects was 34% higher than in UT (46.5 ± 7.0; P < 0.05), and a reduction in PO resulted in a significant increase in MCR by 46% (LT-10%, 91.5 ± 14.9, P < 0.05). At matched relative exercise intensities (67% Vo2max), MCR in T subjects was 97% higher than in UT (P < 0.05). During the LC trial, MCR in T subjects was 64% higher than in UT (P < 0.05), in whom %Vo2max and [lactate]b were similar. We conclude that 1) lactate MCR reaches an apex below the LT, 2) LT corresponds to a limitation in MCR, and 3) endurance training augments capacities for lactate production, disposal and clearance.

Because the maintenance of glycemia is essential during prolonged exercise, we examined the effects of endurance training, exercise intensity, and plasma lactate concentration ([lactate]) on gluconeogenesis (GNG) and hepatic glycogenolysis (GLY) in fasted men exercising at, and just below, the lactate threshold (LT), where GNG precursor lactate availability is high. Twelve healthy men (6 untrained, 6 trained) completed 60 min of constant-load exercise at power outputs corresponding to their individual LT. Trained subjects completed two additional 60-min sessions of constant-load exercise: one at 10% below the LT workload (LT-10%), and the other with a lactate clamp (LT-10%+LC) to match the [lactate] of the LT trial. Flux rates were determined by primed continuous infusion of [6,6-(2)H(2)]glucose, [3-(13)C]lactate, and [(13)C]bicarbonate tracers during 90 min of rest and 60 min of cycling. Exercise at LT corresponded to 67.6 ± 1.3 and 74.8 ± 1.7% peak O(2) consumption in the untrained and trained subjects, respectively (P < 0.05). Relative exercise intensity was matched between the untrained group at LT and the trained group at LT-10%, and [lactate] during exercise was matched in the LT and LT-10%+LC trials via exogenous lactate infusion. Glucose kinetics (rate of appearance, rate of disposal, and metabolic clearance rate) were augmented with the lactate clamp. GNG was decreased in the trained subjects exercising at LT and LT-10% compared with the untrained subjects, but increasing [lactate] in the LT-10%+LC trial significantly increased GNG (4.4 ± 0.9 mg·kg(-1)·min(-1)) compared with its corresponding control (1.7 ± 0.4 mg·kg(-1)·min(-1), P < 0.05). Hepatic GLY was higher in the trained than untrained subjects, but not significantly different across conditions. We conclude that GNG plays an essential role in maintaining total glucose production during exercise in fasted men, regardless of training state. However, endurance training increases the ability to achieve a higher relative exercise intensity and absolute power output at the LT without a significant decrease in GNG. Furthermore, raising systemic precursor substrate availability increases GNG during exercise, but not at rest.

Lactate has been shown to be an important oxidative fuel. We aimed to quantify the total lactate oxidation rate (Rox) and its direct vs. indirect (glucose that is gluconeogenically derived from lactate and subsequently oxidized) components (mg·kg(-1)·min(-1)) during rest and exercise in humans. We also investigated the effects of endurance training, exercise intensity, and blood lactate concentration ([lactate]b) on direct and indirect lactate oxidation. Six untrained (UT) and six trained (T) men completed 60 min of constant load exercise at power outputs corresponding to their lactate threshold (LT). T subjects completed two additional 60-min sessions of constant load exercise at 10% below the LT workload (LT-10%), one of which included a lactate clamp (LC; LT-10%+LC). Rox was higher at LT in T [22.7 ± 2.9, 75% peak oxygen consumption (Vo2peak)] compared with UT (13.4 ± 2.5, 68% Vo2peak, P < 0.05). Increasing [lactate]b (LT-10%+LC, 67% Vo2peak) significantly increased lactate Rox (27.9 ± 3.0) compared with its corresponding LT-10% control (15.9 ± 2.2, P < 0.05). Direct and indirect Rox increased significantly from rest to exercise, and their relative partitioning remained constant in all trials but differed between T and UT: direct oxidation comprised 75% of total lactate oxidation in UT and 90% in T, suggesting the presence of training-induced adaptations. Partitioning of total carbohydrate (CHO) use showed that subjects derived one-third of CHO energy from blood lactate, and exogenous lactate infusion increased lactate oxidation significantly, causing a glycogen-sparing effect in exercising muscle.

Johnson ML, Emhoff CW, Horning MA, Brooks GA. Transpulmonary lactate shuttle. Am J Physiol Regul Integr Comp Physiol 302: R143-R149, 2012. First published October 26, 2011 doi:10.1152/ajpregu.00402.2011.-The shuttling of intermediary metabolites such as lactate through the vasculature contributes to the dynamic energy and biosynthetic needs of tissues. Tracer kinetic studies offer a powerful tool to measure the metabolism of substrates like lactate that are simultaneously taken up from and released into the circulation by organs, but in each circulatory passage, the entire cardiac output traverses the pulmonary parenchyma. To determine whether transpulmonary lactate shuttling affects whole-body lactate kinetics in vivo, we examined the effects of a lactate load (via lactate clamp, LC) and epinephrine (Epi) stimulation on transpulmonary lactate kinetics in an anesthetized rat model using a primedcontinuous infusion of [U-13 C]lactate. Under all conditions studied, control 1.2 (SD 0.7) (Con), LC 1.9 (SD 2.5), and Epi 1.9 (SD 3.5) mg/min net transpulmonary lactate uptake occurred. 3) conditions, but negative during Epi stimulation, Ϫ25.3% (SD 45.5) when there occurred a transpulmonary production, the conversion of mixed central venous pyruvate to arterial lactate. Further, isotopic equilibration between L and P occurred following tracer lactate infusion, but depending on compartment (v or a) and physiological stimulus, [L]/[P] concentration and isotopic enrichment ratios ranged widely. We conclude that pulmonary arterial-vein concentration difference measurements across the lungs provide an incomplete, and perhaps misleading picture of parenchymal lactate metabolism, especially during epinephrine stimulation. lactate metabolism; lung; pyruvate metabolism; lactate kinetics EARLY RESEARCHERS DEMONSTRATED the ability of the lungs to produce lactate from glucose under fully aerobic conditions (9). Subsequent work identified the lungs as a complex metabolic organ with respect to carbohydrate intermediary metabolism; at times, the lungs were net consumers of lactate, while at other times, such as in patients with acute respiratory distress syndrome, the lungs released lactate on a net basis (1-3, 7, 20). In contrast, many studies were unable to show transpulmonary net uptake or release. Such determinations are complicated due to the high blood flow through the pulmonary circulation in relation to metabolic requirements of lung parenchyma (11, 23). Using [U-14 C]glucose and an isolated perfused rat lung preparation Longmore and Mourning (22) demonstrated that the majority of lactate released during aerobic conditions was derived from glucose. However, upon exposure to hypoxia, lactate production nearly doubled in the preparation, but with only 60% of the lactate produced coming from glucose. When previously hypoxic lungs were reexposed to aerobic conditions, lactate release reverted to production exclusively from glucose. The work of Longmore and Mourning illustrates the diverse metabolic properties of lungs under condit...