Metabolic and cardiorespiratory responses  to “the lactate clamp”

Miller, Benjamin F.; Fattor, Jill A.; Jacobs, Kevin A.; Horning, Michael A.; Suh, Sang Hoon; Navazio, F; Brooks, George A.

doi:10.1152/ajpendo.00266.2002

Cited by 62 publications

(123 citation statements)

References 42 publications

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“…We observed a significant decrease of blood glucose concentration during exercise from 5.0 to 4.2 mM after 4 h. A decrease of similar extent has been reported by others, albeit in humans performing exercise at higherintensity levels, up to 65% V O 2 max (15,28,29,44,45). In those studies, subjects were studied 7.5 h after their last meal, and exercise commenced 12 h following completion of their evening meal.…”

Section: H Enrichment In Body Water and At C-5 Of Glucose And Estimatsupporting

confidence: 89%

“…Differences in physiological state could also explain the difference between our findings (obtained during prolonged low-intensity exercise) and those of previous studies (obtained in subjects under resting conditions). Recently, Miller and colleagues (28,29) studied the effect of hyperlactatemia due to lactate infusion (lactate clamp) in healthy volunteers at rest and under exercise at moderate and high intensity. In contrast to our observations, they found a decrease in glucose R a during lactate infusion under exercise.…”

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confidence: 99%

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Gluconeogenesis in humans with induced hyperlactatemia during low-intensity exercise

Roef¹,

Meer

Kalhan

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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We studied the role of lactate in gluconeogenesis (GNG) during exercise in untrained fasting humans. During the final hour of a 4-h cycle exercise at 33-34% maximal O 2 uptake, seven subjects received, in random order, either a sodium lactate infusion (60 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) or an isomolar sodium bicarbonate infusion. The contribution of lactate to gluconeogenic glucose was quantified by measuring 2 H incorporation into glucose after body water was labeled with deuterium oxide, and glucose rate of appearance (Ra) was measured by [6,6-2 H2]glucose dilution. Infusion of lactate increased lactate concentration to 4.4 Ϯ 0.6 mM (mean Ϯ SE). Exercise induced a decrease in blood glucose concentration from 5.0 Ϯ 0.2 to 4.2 Ϯ 0.3 mM (P Ͻ 0.05); lactate infusion abolished this decrease (5.0 Ϯ 0.3 mM; P Ͻ 0.001) and increased glucose Ra compared with bicarbonate infusion (P Ͻ 0.05). Lactate infusion increased both GNG from lactate (29 Ϯ 4 to 46 Ϯ 4% of glucose Ra, P Ͻ 0.001) and total GNG. We conclude that lactate infusion during low-intensity exercise in fasting humans 1) increased GNG from lactate and 2) increased glucose production, thus increasing the blood glucose concentration. These results indicate that GNG capacity is available in humans after an overnight fast and can be used to sustain blood glucose levels during low-intensity exercise when lactate, a known precursor of GNG, is available at elevated plasma levels. lactate; hyperlactatemia; stable isotopes GLUCONEOGENESIS (GNG) is regulated by hormones (such as glucagon and insulin) and requires three-carbon substrates, i.e., pyruvate (from lactate and alanine) or glycerol. The relationship among substrate availability, the rate of GNG, and the concentration of the product, glucose, in the blood is not yet fully understood. Increased lactate concentration in blood is known to occur in a number of metabolic disorders, e.g., respiratory chain disorders, pyruvate dehydrogenase deficiency, and diabetes mellitus (13). The role of GNG under the condition of increased substrate availability in these disorders is of pathophysiological interest. In patients with a respiratory chain disorder, plasma lactate concentrations are substantially increased at low-intensity levels of exercise (35,36); in patients with mitochondrial myopathy due to complex I deficiency, we observed steady-state plasma lactate concentrations of between 4 and 7 mM during prolonged low-intensity cycle exercise at 15% of their maximal workload (W max ). Their mean lactate rate of appearance (R a ) was 73 Ϯ 12 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 during exercise, which was more than double their resting lactate R a (35,36). In another low-intensity exercise study in mitochondrial myopathy patients with complex I deficiency during fasting, plasma lactate concentrations increased from 1 mM at rest to ϳ4 mM during exercise and were associated with an increased fractional contribution of lactate to glucose production as well as increased rates of glucose production (37).In healthy human subjects in the resting condition...

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Section: H Enrichment In Body Water and At C-5 Of Glucose And Estimatsupporting

confidence: 89%

mentioning

confidence: 99%

Gluconeogenesis in humans with induced hyperlactatemia during low-intensity exercise

Roef¹,

Meer

Kalhan

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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“…In the process of shuttling between sites of production and removal, lactate exerts profound effects on fat and CHO metabolism. Because lactate is a preferred fuel over glucose in the heart [69], working muscle [4,70,71] and brain [72], hyperlactatemia affects glucose uptake and oxidation by substituting for pyruvate and lactate produced from glycolysis in widely dispersed tissues. Lactate is oxidized via the mitochondrial lactate oxidation complex (mLOC) comprising the monocarboxylate transporter-1 (MCT1), its chaperone (CD147), mitochondrial lactate dehydrogenase (mLDH), and cytochrome oxidase (COx) [73,74].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Metabolic Flexibility by Means of Measuring Blood Lactate, Fat, and Carbohydrate Oxidation Responses to Exercise in Professional Endurance Athletes and Less-Fit Individuals

San-Millán

Brooks²

2017

Sports Med

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197

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Background Increased muscle mitochondrial mass is characteristic of elite professional endurance athletes (PAs), whereas increased blood lactate levels (lactatemia) at the same absolute submaximal exercise intensities and decreased mitochondrial oxidative capacity are characteristics of individuals with low aerobic power. In contrast to PAs, patients with metabolic syndrome (MtS) are characterized by a decreased capacity to oxidize lipids and by early transition from fat to carbohydrate oxidation (FATox/ Key PointsMeasurements of blood lactate concentration and fat oxidation (FATox) provide an indirect method to assess metabolic flexibility, mitochondrial function, and oxidative capacity during exercise in different populations.The inverse correlations between blood lactate and FATox are quite robust, therefore assessing blood lactate alone could be an effective way to indirectly assess mitochondrial function and metabolic flexibility during exercise in different populations.Since lactate exerts profound effects on fat and carbohydrate (CHO) metabolism, a poor mitochondrial lactate clearance capacity due to decreased mitochondrial function could greatly affect FATox and CHOox, which could result in metabolic dysregulation, which in turn could lead to different metabolic diseases such as type 2 diabetes.

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“…Previous reports showed that an increase in blood lactate induced changes in the concentration of blood catecholamine and whole-body glucose metabolism (13)(14)(15). These findings indicate the role of lactate as an index for monitoring energy metabolism, and that increase in lactate affects energy metabolism.…”

Section: Discussionmentioning

confidence: 56%

Blood Lactate Functions as a Signal for Enhancing Fatty Acid Metabolism during Exercise via TGF-^|^beta; in the Brain

Yamada

Iwaki

Kitaoka

et al. 2012

J Nutr Sci Vitaminol

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Summary Moderate-intensity running (treadmill velocity of 21 m/min) increased blood lactate and actived transforming growth factor-␤ (TGF-␤ ) concentration in rat cerebrospinal fluid (CSF). On the other hand, low-intensity running (15 m/min) did not increase blood lactate and caused no change in CSF TGF-␤ . Intraperitoneal (i.p.) administration of lactate to anesthetized rats caused an increase in blood lactate similar to that observed after a 21 m/min running exercise and increased the level of active TGF-␤ in CSF. Intraperitoneal administration of lactate at the same dose to awake and unrestricted rats caused a decrease in the respiratory exchange ratio, that is, enhancement of fatty acid oxidation and depression of spontaneous motor activity (SMA). Given that intracisternal administration of TGF-␤ to rats has been reported to enhance fatty acid metabolism and to depress SMA, we surmise that the observed changes caused by i.p. lactate administration in this study were mediated, at least in part, by TGF-␤ in the brain. Key Words lactate, TGF-␤ , exercise, respiratory gas analysis, spontaneous motor activity Recently, lactate has been recognized as a good energy source for the central nervous system. Wyss et al.( 1 ) demonstrated that lactate instead of glucose could maintain neuronal activities, and that when both substrates are available, the brain preferentially utilizes lactate. The study, however, implies that lactate is not a direct cause of feelings of fatigue by acting on the brain, and negated the classical view of lactate as a fatigue substance. Blood lactate increases during physical exercise, with skeletal muscles being the major sites of lactate production [see Bergersen ( 2 ) for review]. Increased lactate concentration serves as a signal indicating an increase in the relative ratio of glycolytic energy production, and this signal may function to induce changes in whole-body energy metabolism. Lactate directly acts on neurons and affects their activities. The activities of some neurons in the ventromedial hypothalamus are affected by glucose, whereas some neurons show increased firing rate upon lactate administration ( 3 ). Patil and Briski ( 4 , 5 ) reported the activation of catecholaminergic neurons in the hindbrain by blocking the supply of lactate into the brain with ␣ -cyano-4-hydroxycinnamic acid. These findings indicate that lactate functions as an index for monitoring the energy metabolism status of peripheral organs.We developed a model (Sim-Ex) that simulates physical exercise by inducing skeletal muscle contraction through electrical stimulation in the hindlimbs of anesthetized rats ( 6 ). Sim-Ex with a frequency of 2 Hz could reproduce an exercise load that corresponded to lowintensity exercise. We reported significant increases in the concentrations of blood lactate and active transforming growth factor-␤ (TGF-␤ ) in cerebrospinal fluid (CSF) 5 and 10 min after the onset of Sim-Ex, respectively ( 7 ). A fraction of active TGF-␤ increased in rat CSF after exhaustion by exercise ( 8 ). ...

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Metabolic and cardiorespiratory responses to “the lactate clamp”

Cited by 62 publications

References 42 publications

Gluconeogenesis in humans with induced hyperlactatemia during low-intensity exercise

Gluconeogenesis in humans with induced hyperlactatemia during low-intensity exercise

Assessment of Metabolic Flexibility by Means of Measuring Blood Lactate, Fat, and Carbohydrate Oxidation Responses to Exercise in Professional Endurance Athletes and Less-Fit Individuals

Blood Lactate Functions as a Signal for Enhancing Fatty Acid Metabolism during Exercise via TGF-^|^beta; in the Brain

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