Brain Lactate Is an Obligatory Aerobic Energy Substrate for Functional Recovery After Hypoxia: Further In Vitro Validation

Schurr, Avital; Payne, Ralphiel S.; Miller, James J.; Rigor, Benjamin M.

doi:10.1046/j.1471-4159.1997.69010423.x

Cited by 239 publications

(146 citation statements)

References 15 publications

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“…This view has been challenged recently, and lactate has emerged as an alternative CNS energy source during times of energy deficit. For example, lactate is an obligatory energy substrate for recovery of neuronal function after hypoxia-ischemia (15). Insulin-induced hypoglycemia increases lactate utilization in the brain (10), and local perfusion of lactate into the VMN suppresses the counterregulatory response to hypoglycemia (11).…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Glucose and Lactate on Glucosensing Neurons in the Ventromedial Hypothalamic Nucleus

2005

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Glucose directly alters the action potential frequency of glucosensing neurons in the ventromedial hypothalamic nucleus (VMN). Glucose-excited neurons increase, and glucose-inhibited neurons decrease, their action potential frequency as glucose increases from 0.1 to 2.5 mmol/l. Glucose-excited neurons utilize the ATP-sensitive K ؉ channel (K ATP channel) to sense glucose, whereas glucose opens a chloride channel in glucoseinhibited neurons. We tested the hypothesis that lactate, an alternate energy substrate, also regulates the action potential frequency of VMN glucose-excited and -inhibited but not nonglucosensing neurons. As expected, lactate reversed the inhibitory effects of decreased glucose on VMN glucose-excited neurons via closure of the K ATP channel. Although increasing glucose from 2.5 to 5 mmol/l did not affect the activity of glucose-excited neurons, the addition of 0.5 mmol/l lactate or the K ATP channel blocker tolbutamide increased their action potential frequency. In contrast to the glucose-excited neurons, lactate did not reverse the effects of decreased glucose on VMN glucose-inhibited neurons. In fact, it increased their action potential frequency in both low and 2.5 mmol/l glucose. This effect was mediated by both K ATP and chloride channels. Nonglucosensing neurons were not affected by lactate. Thus, glucose and lactate have similar effects on VMN glucose-excited neurons, but they have opposing effects on VMN glucose-inhibited neurons. Diabetes 54:15-22, 2005 T he ventromedial hypothalamic nucleus (VMN) plays an important role in the central regulation of glucose homeostasis (1). Electrical stimulation of the ventromedial hypothalamus (VMH), which contains the VMN, activates the sympathoadrenal system in a manner similar to that seen during initiation of the counterregulatory response to hypoglycemia (2). Moreover, local VMH glucopenia caused by delivery of the nonmetabolizable glucose analog 2-deoxyglucose into the VMH causes the release of counterregulatory hormones (3). In contrast, glucose infusion into the VMH suppresses their release during systemic hypoglycemia (4). We have described five subtypes of VMN glucosensing neurons that alter their action potential frequency in response to physiological changes in extracellular glucose from 2.5 to 0.1 or 5 mmol/l (5). Of these VMN glucosensing neurons, two subtypes are directly sensitive to decreases in extracellular glucose levels; glucose-excited neurons increase whereas glucose-inhibited neurons decrease their action potential frequency as extracellular glucose increases from 0.1 to 2.5 mmol/l (5). Like pancreatic ␤-cells, about half of both VMN glucose-excited and -inhibited neurons appear to utilize a special hexokinase known as glucokinase to sense glucose (6). The actual response to glucose is mediated by the ATP-sensitive K ϩ (K ATP channel) and a Cl Ϫ channel for glucose-excited and -inhibited neurons, respectively (5).Lactate may be an alternate energy source in the brain (7-9). Both neurons and astrocytes produce lactate (7). In ...

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Section: Discussionmentioning

confidence: 99%

Differential Effects of Glucose and Lactate on Glucosensing Neurons in the Ventromedial Hypothalamic Nucleus

2005

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“…32 As a result, epinephrine stimulation promotes high rates of aerobic glycolysis, allowing organs such as the heart and the brain to maintain specific functions that require a high rate of cytoplasmic ATP. 33,34 Further investigations on pathological conditions affecting skeletal muscles have illustrated the importance of the ADRB2 gene in the regulation of skeletal muscle function. A study by Xu et al 35 observed a significant disequilibrium between ADRB2 polymorphisms at amino-acid positions 16 and 27, and a greater incidence of Myasthenia Gravis in homozygous Arg16 patients.…”

Section: Musculoskeletal Systemmentioning

confidence: 99%

Adrenergic-β2 receptor polymorphism and athletic performance

Sarpeshkar

Bentley

2010

J Hum Genet

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The focus of this review is to evaluate the influence of b 2 -adrenergic receptor (ADRB2) polymorphism on human physiological function and in turn on athletic performance. A narrative review is conducted on available literature using MedLine, Pubmed and the Cochrane Library to document the location and function of ADRB2 receptors, and specifically to address the influence of genetic polymorphisms on cardiovascular, respiratory, metabolic and musculoskeletal systems and athletic performance. Search terms included ADRB2, endurance and polymorphism. Previous literature exploring the genetic composition of athletes has proposed that alterations in the genetic structure result in an enhancement in their capacity to achieve successful aerobic phenotypes such as a higher VO 2max and increased fat oxidation. Polymorphism of the Gly16Glu27 haplotype is believed to promote positive aerobic phenotypes and regulate optimal lipolysis. Greater knowledge of the ADRB2 polymorphism can aid in understanding the specific phenotypes that are altered, which may influence performance. Until the interaction between fatigue and athletic performance is better understood, the development of appropriate training principles to enhance genetically polymorphic aerobic phenotypes remains complicated. Following the review, there is still no distinctive evidence for the predictive ability of the polymorphism of ADRB2 genotype for the purpose of identifying potential elite athletes.

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“…As for lactate serving as a precursor for biosynthesis, gluconeogenesis in astrocytes and neurons is negligible (Swanson et al, 1990) and glycogen synthesis from lactate does not appear to be significant (Brown et al, 2003;Ide et al, 1969). In regard to metabolism, infusion of lactate spares glucose in resting subjects (Smith et al, 2003), and after exercise (Kemppainen et al, 2005) and on the cellular level lactate is metabolised by both neurons (Schurr et al, 1997) and astrocytes (Dringen et al, 1995). Conversion of lactate to pyruvate and subsequent oxidation yields energy metabolites that may inhibit glycolysis (Ide et al, 1969;Tabernero et al, 1996), which could explain the glucosesparing effect of lactate (Bouzier-Sore et al, 2003;Kemppainen et al, 2005;Smith et al, 2003).…”

Section: The Brain In Exercisementioning

confidence: 99%

Fuelling Cerebral Activity in Exercising Man

Dalsgaard

2005

J Cereb Blood Flow Metab

137

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The metabolic response to brain activation in exercise might be expressed as the cerebral metabolic ratio (MR; uptake O 2 /glucose + 1/2 lactate). At rest, brain energy is provided by a balanced oxidation of glucose as MR is close to 6, but activation provokes a 'surplus' uptake of glucose relative to that of O 2 . Whereas MR remains stable during light exercise, it is reduced by 30% to 40% when exercise becomes demanding. The MR integrates metabolism in brain areas stimulated by sensory input from skeletal muscle, the mental effort to exercise and control of exercising limbs. The MR decreases during prolonged exhaustive exercise where blood lactate remains low, but when vigorous exercise raises blood lactate, the brain takes up lactate in an amount similar to that of glucose. This lactate taken up by the brain is oxidised as it does not accumulate within the brain and such pronounced brain uptake of substrate occurs independently of plasma hormones. The 'surplus' of glucose equivalents taken up by the activated brain may reach B10 mmol, that is, an amount compatible with the global glycogen level. It is suggested that a low MR predicts shortage of energy that ultimately limits motor activation and reflects a biologic background for 'central fatigue'.

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Brain Lactate Is an Obligatory Aerobic Energy Substrate for Functional Recovery After Hypoxia: Further In Vitro Validation

Cited by 239 publications

References 15 publications

Differential Effects of Glucose and Lactate on Glucosensing Neurons in the Ventromedial Hypothalamic Nucleus

Differential Effects of Glucose and Lactate on Glucosensing Neurons in the Ventromedial Hypothalamic Nucleus

Adrenergic-β2 receptor polymorphism and athletic performance

Fuelling Cerebral Activity in Exercising Man

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