2018
DOI: 10.1007/s00421-017-3795-6
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Lactate metabolism: historical context, prior misinterpretations, and current understanding

Abstract: Lactate (La) has long been at the center of controversy in research, clinical, and athletic settings. Since its discovery in 1780, La has often been erroneously viewed as simply a hypoxic waste product with multiple deleterious effects. Not until the 1980s, with the introduction of the cell-to-cell lactate shuttle did a paradigm shift in our understanding of the role of La in metabolism begin. The evidence for La as a major player in the coordination of whole-body metabolism has since grown rapidly. La is a re… Show more

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Cited by 283 publications
(327 citation statements)
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“…Investigators have substantially revised their ideas about lack of oxygen as responsible for lactate production during exercise (Ferguson et al. ). Originally regarded as a “hypoxic waste product”, many clinicians still view lactate in this manner.…”
Section: Discussionmentioning
confidence: 99%
“…Investigators have substantially revised their ideas about lack of oxygen as responsible for lactate production during exercise (Ferguson et al. ). Originally regarded as a “hypoxic waste product”, many clinicians still view lactate in this manner.…”
Section: Discussionmentioning
confidence: 99%
“…Among these metabolic changes, blood acidosis has been identified in several in vitro and in vivo studies as a strong potential triggering factor for RBC sickling (Greenberg & Kass, ; Greenberg, Kass, & Castle, ; Lange, Minnich, & Moore, ). Given that muscle exercise is tightly linked to intra‐ and extracellular acidosis resulting from the non‐oxidative glycolytic processes of energy production (Bangsbo et al., ; Bangsbo, Johansen, Graham, & Saltin, ; Brooks, ; Ferguson et al., ; Hermansen & Osnes, ; Juel, ; Marcinek, Kushmerick, & Conley, ; Osnes & Hermansen, ; Sahlin, ; Sahlin, Alvestrand, Brandt, & Hultman, ; Sahlin, Harris, Nylind, & Hultman, ), one can wonder whether physical activity could be deleterious for SCD patients. To prevent the occurrence of any associated risks, extending our knowledge about the potential deleterious effects of muscle exercise in SCD patients is of great interest, particularly given that rehabilitation based on physical activity is increasingly considered as a potential therapeutic strategy in this pathology (Liem, Akinosun, Muntz, & Thompson, ; Martin et al., ).…”
Section: Sickle Cell Diseasementioning
confidence: 99%
“…While these studies certainly highlight the importance of lactate uptake in brain function, additional work is needed to parse the directionality of lactate transport and underlying mechanisms of neuroprotection. Considering the widespread controversy over the existence of the ANLS (Chih et al, ; Chih & Roberts, ; Dienel, ; Dienel & Cruz, ; Ferguson et al, ; Riske et al, ; Yellen, ), it is worthwhile to consider the underlying assumptions and open questions regarding the hypothesized model in which axons rely on oligodendrocyte‐derived lactate. Specifically, the current model rests on three primary assumptions: (a) post‐myelination oligodendrocytes favor aerobic glycolysis, leading to a high intracellular lactate concentration relative to the periaxonal space; (b) myelinated axons exhibit a low intracellular lactate concentration relative to the periaxonal space; and (c) myelinated axons metabolize oligodendrocyte‐derived lactate.…”
Section: Energetic Coupling Of Glia and Axonsmentioning
confidence: 99%
“…In order for lactate to be imported into myelinated axons, axonal lactate concentration must be low relative to the periaxonal space. As discussed previously, whether neurons primarily utilize oxphos or glycolysis and under what activation states is a highly controversial matter (Chih et al, ; Chih & Roberts, ; Dienel, ; Dienel & Cruz, ; Ferguson et al, ; Riske et al, ; Yellen, ). Considering the heterogenous findings between intracellular compartments and resting versus stimulated nerve cells, it seems imperative to interpret results only within the context measured.…”
Section: Energetic Coupling Of Glia and Axonsmentioning
confidence: 99%
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