Metabolic interactions of glucose, lactate, and beta-hydroxybutyrate in rat brain slices

Ide, Tomohiro; Steinke, Jürgen; Gf, Cahill

doi:10.1152/ajplegacy.1969.217.3.784

Cited by 89 publications

(43 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus from studies with different animal models including the rat and dog we are led to predict that hypoxia in the mouse involves an initial (8) (10) • BHB gjBHB&QQ =BHB&QLU 5£BHB&GLU&GQ compromise of brain function followed by respiratory and then cardiovascular collapse. Our values for CO 2 production and lipid formation in slices bubbled with 95% oxygen are consistent with those of Ide et al 20 and confirm that addition of glucose to the incubation medium increases the incorporation of BHB into CO 2 and the addition of BHB to the medium decreases the incorporation of glucose into CO 2 . Thus the values (absolute and relative) we have obtained with the brain slice preparation indicate effective use of this model for measurement of brain metabolism.…”

Section: Methodological Considerationssupporting

confidence: 92%

“…The 95% oxygen level was chosen so that we could compare our values of CO 2 production to those in the literature. 20 Since the CO 2 production from brain slices utilizing glucose was the same at 95% oxygen and 40% oxygen but reduced when at 5% oxygen we predict that the 95% oxygen was not damaging or limiting to the slice but the 5% oxygen became a limiting factor. Thus in both the slice preparation and the mouse model there is a transition from adequate oxygen for function to hypoxic dysfunction.…”

Section: Methodological Considerationsmentioning

confidence: 95%

“…Unmedicated, adult male Sprague-Dawley rats (457 ± 19 g, n = 54) fed ad libitum were decapitated and the brain quickly removed into iced incubation medium which was a modified Krebs-Ringer bicarbonate buffer solution described by Ide et al (20) containing Na, 146; K, 5; Ca, 2; Mg, 1; Cl, 113; HPO 4 , 1 and HCO 3 40 mM. The dura and arachnoid were removed and the brain was sliced with an automatic tissue slicer (Mcllwain, Beckman) to obtain, from each hemisphere, four 0.3 mm thick cortical slices (total average wet weight 37.4 ± 0.7 mg, n = 108) which were placed in 2.2 ml of medium in a 25 ml incubation flask (Kontos Glass Company).…”

Section: Brain Slice Preparationmentioning

confidence: 99%

“…Capped flasks were incubated in a shaker bath for 2 hours at 37°C and 72 cycles/minute after which 0.2 ml of 10 N H 2 SO 4 and 0.3 ml of 1 M methylbenzethonium hydroxide in methanol were injected through the stopper into the medium and center well respectively. The collection of CO 2 was considered complete after 90 minutes of additional incubation at room temperature and 36 cycles/ minute (20). The well containing the trapped CO 2 was placed in 10 ml of ACS liquid scintilation fluid (Amersham Inc.), capped, mixed by vortex and placed in a beta counter (Searle Isocap/300) for 30 minutes prior to counting to allow for loss of chemiluminescence.…”

Section: Brain Slice Preparationmentioning

confidence: 99%

See 3 more Smart Citations

Glucagon stimulates ketone utilization by rat brain slices.

Kirsch¹,

DʼAlecy²

1984

Stroke

View full text Add to dashboard Cite

SUMMARY Glucagon has been shown previously to increase further the enhanced tolerance for hypoxia observed in mice with elevated blood ketones. Glucagon is also known to increase blood glucose and to alter directly the metabolism of some (liver) cells. Both the increase in blood glucose and altered cellular metabolism could contribute to the increase in tolerance for hypoxia observed in mice given glucagon in combination with the ketone, beta-hydroxybutyrate. To evaluate the systemic component of this hypothesis, blood glucose, beta-hydroxybutyrate, and glucagon were elevated alone or simultaneously and hypoxic tolerance of mice was measured. To identify possible cellular effects of glucagon on glucose or ketone metabolism, we measured the incorporation of radiolabled glucose or beta-hydroxybutyrate into CO 2 or total lipid in isolated rat brain slices. Both glucagon and glucose increased hypoxic tolerance of ketotic mice but our data do not support the hypothesis that glucagon's action was only through an elevation of blood glucose. In brain slices glucagon stimulated the incorporation of beta-hydroxybutyrate into CO 2 both in the presence or absence of additional glucose. These results demonstrate that glucagon has a direct effect on brain metabolism which may contribute to the increased tolerance for hypoxia. They, however, do not exclude the possibility that glucagon is working in addition to increase hypoxic survival in ketotic mice by increasing the availability of glucose to the brain. Stroke Vol 15, No 2, 1984CONTEMPORARY THERAPEUTIC MEASURES for hypoxic-ischemic brain injury involve anticoagulation, antiplatelet agents, volume expansion, hemodilution, induced hypertension, pharmacological vasodilators, barbiturate coma, profound cooling, steroids, diuretics and a variety of other miscellaneous treatments. None of these procedures have met with resounding success. We believe our work on induced ketosis represents a fundamentally different approach to the problem of cerebral protection.Previous studies from our laboratory demonstrated that, when mice were placed in an hypoxic environment, those with elevated blood ketones survived up to five times longer. 1 -2 Furthermore, this enhanced hypoxic tolerance was potentiated by exogenous glucagon (GG). 3 Before such manipulations of blood glucose, ketones or GG can be considered for clinical applicability, some basic understanding of the mechanism by which these procedures increase tolerance for hypoxia would be desirable.In the intact animal GG is known not only to elevate blood glucose but to alter cellular metabolism. 4 For example, it has been reported that acute GG treatment of intact animals alters liver mitochondrial calcium flux and respiration. 3 Furthermore, Suzuki 6 reported that the intravenous injection of GG increases oxygen consumption of subsequently prepared liver slices. In order to discriminate between a direct cellular effect and an indirect systemic effect of GG, Siess and Wieland 7 first isolated hepatocytes and then treated them with GG....

show abstract

Section: Methodological Considerationssupporting

confidence: 92%

Section: Methodological Considerationsmentioning

confidence: 95%

Section: Brain Slice Preparationmentioning

confidence: 99%

Section: Brain Slice Preparationmentioning

confidence: 99%

See 2 more Smart Citations

Glucagon stimulates ketone utilization by rat brain slices.

Kirsch¹,

DʼAlecy²

1984

Stroke

View full text Add to dashboard Cite

show abstract

“…This effect has been demonstrated in incubated rat brain slices (33,34) and brain cell cultures (35,36) and in vivo by using i.v. (37,38) or i.p.…”

Section: Discussionmentioning

confidence: 83%

Increased lactate/pyruvate ratio augments blood flow in physiologically activated human brain

Mintun

Vlassenko

Rundle

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

131

104

View full text Add to dashboard Cite

The factors regulating cerebral blood flow (CBF) changes in physiological activation remain the subject of great interest and debate. Recent experimental studies suggest that an increase in cytosolic NADH mediates increased blood flow in the working brain. Lactate injection should elevate NADH levels by increasing the lactate͞ pyruvate ratio, which is in near equilibrium with the NADH͞NAD ؉ ratio. We studied CBF responses to bolus lactate injection at rest and in visual stimulation by using positron-emission tomography in seven healthy volunteers. Bolus lactate injection augmented the CBF response to visual stimulation by 38 -53% in regions of the visual cortex but had no effect on the resting CBF or the wholebrain CBF. These lactate-induced CBF increases correlated with elevations in plasma lactate͞pyruvate ratios and in plasma lactate levels but not with plasma pyruvate levels. Our observations support the hypothesis that an increase in the NADH͞NAD ؉ ratio activates signaling pathways to selectively increase CBF in the physiologically stimulated brain regions.T he nature of the link between cerebral blood flow (CBF) and energy metabolism is of great interest and importance but remains controversial despite decades of research and debate. Although CBF augmentation is still considered to be a hallmark of intensified neural activity, previous assumptions that behaviorally induced increases in local blood flow reflect similar local increases in oxidative metabolism (1) have been contradicted by brain imaging studies with positron-emission tomography (PET) (2, 3) and functional MRI (4). Fox and his colleagues (2, 3) demonstrated that in normal, awake adult humans, stimulation of the visual or somatosensory cortex results in dramatic increases in CBF but minimal increases in oxygen consumption. Increases in glucose utilization are similar to changes in CBF (3, 5). Although it is often assumed that the increase in CBF in neural activation is driven by a need for increased delivery of oxygen or glucose, it has been demonstrated in human subjects that the CBF response to physiological activation is not altered by either stepped hypoglycemia (6) or hypoxia (7). These results suggest that increased CBF during physiological brain activation does not occur to prevent a shortage of these metabolic substrates. Ido et al. (8) recently reported that CBF in activated rat brain is modified by changes in the plasma lactate͞pyruvate ratio: CBF was augmented when lactate͞pyruvate ratios were raised and attenuated when the ratios were lowered. Specifically, immediately after lactate bolus injection, the magnitude of the CBF increase associated with sensory stimulation approximately doubled. Based on the near equilibrium between the ratios of lactate͞pyruvate and cytosolic free NADH͞NAD ϩ (which reflects the local environment redox state) (9), they suggested that cytosolic free NADH is an important trigger or sensor of blood flow. The reoxidation of NADH to NAD ϩ is a step of vital importance for brain cells, especially in the acti...

show abstract

Metabolic pathways for glucose in astrocytes

Wiesinger

Hamprecht

Dringen

1997

Glia

166

110

View full text Add to dashboard Cite

Cultured astroglial cells are able to utilize the monosaccharides glucose, mannose, or fructose as well as the sugar alcohol sorbitol as energy fuel. Astroglial uptake of the aldoses is carrier‐mediated, whereas a non‐saturable transport mechanism is operating for fructose and sorbitol. The first metabolic step for all sugars, including fructose being generated by enzymatic oxidation of sorbitol, is phosphorylation by hexokinase. Besides glucose only mannose may serve as substrate for build‐up of astroglial glycogen. Whereas glycogen synthase appears to be present in astrocytes as well as neurons, the exclusive localization of glycogen phosphorylase in astrocytes and ependymal cells of central nervous tissue correlates well with the occurrence of glycogen in these cells. The identification of lactic acid rather than glucose as degradation product of astroglial glycogen appears to render the presence of glucose‐6‐phosphatase in cultured astrocytes an enigma. The colocalization of pyruvate carboxylase, phosphenolpyruvate carboxykinase and fructose‐1,6‐bisphosphatase points to astrocytes as being the gluconeogenic cell type of the CNS. GLIA 21:22–34, 1997. © 1997 Wiley‐Liss, Inc.

show abstract

Metabolic interactions of glucose, lactate, and beta-hydroxybutyrate in rat brain slices

Cited by 89 publications

References 16 publications

Glucagon stimulates ketone utilization by rat brain slices.

Glucagon stimulates ketone utilization by rat brain slices.

Increased lactate/pyruvate ratio augments blood flow in physiologically activated human brain

Metabolic pathways for glucose in astrocytes

Contact Info

Product

Resources

About