Abstract
After almost a century of misunderstanding, it is time to appreciate that lactate shuttling is an important feature of energy flux and metabolic regulation that involves a complex series of metabolic, neuroendocrine, cardiovascular, and cardiac events in vivo. Cell–cell and intracellular lactate shuttles in the heart and between the heart and other tissues fulfill essential purposes of energy substrate production and distribution as well as cell signaling under fully aerobic conditions. Recognition of lactate shuttling came first in studies of physical exercise where the roles of driver (producer) and recipient (consumer) cells and tissues were obvious. One powerful example of cell–cell lactate shuttling was the exchange of carbohydrate energy in the form of lactate between working limb skeletal muscle and the heart. The exchange of mass represented a conservation of mass that required the integration of neuroendocrine, autoregulatory, and cardiovascular systems. Now, with greater scrutiny and recognition of the effect of the cardiac cycle on myocardial blood flow, there brings an appreciation that metabolic fluxes must accommodate to pressure-flow realities within an organ in which they occur. Therefore, the presence of an intra-cardiac lactate shuttle is posited to explain how cardiac mechanics and metabolism are synchronized. Specifically, interruption of blood flow during the isotonic phase of systole is supported by glycolysis and subsequent return of blood flow during diastole allows for recovery sustained by oxidative metabolism.
Highlights
The purported role of lactate in physiology and medicine is a century old, but understanding of the role has changed dramatically in the last three decades [1,2,3,4,5,6,7]
Lactate shuttling between producer and consumer cells requires the presence of cell–cell and intracellular lactate shuttles that fulfill at least three purposes: lactate is [1] a major energy source, [2] the major gluconeogenic precursor, and [3] a signaling molecule
Lactate production occurs during rest and exercise under fully aerobic conditions [26, 28, 60, 93] and increases exponentially as exercise power output increases [55]
Summary
The purported role of lactate in physiology and medicine is a century old, but understanding of the role has changed dramatically in the last three decades [1,2,3,4,5,6,7]. Lactate shuttling between producer (driver) and consumer (recipient) cells requires the presence of cell–cell and intracellular lactate shuttles that fulfill at least three purposes: lactate is [1] a major energy source, [2] the major gluconeogenic precursor, and [3] a signaling molecule.
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