scholarly journals Direct Measurement of the λ of the Lumped Constant of the Deoxyglucose Method in Rat Brain: Determination of λ and Lumped Constant from Tissue Glucose Concentration or Equilibrium Brain/Plasma Distribution Ratio for Methylglucose

1991 ◽  
Vol 11 (1) ◽  
pp. 25-34 ◽  
Author(s):  
Gerald A. Dienel ◽  
Nancy F. Cruz ◽  
Kentaro Mori ◽  
James E. Holden ◽  
Louis Sokoloff
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Full Range ◽  
Acid Extraction ◽  
Distribution Space ◽  
Glucose Levels ◽  
Lumped Constant ◽  
Distribution Spaces ◽  
The Brain

Steady-state distribution spaces of 2-[14C]deoxyglucose ([14C]DG), glucose, and 3- O-[14C]methylglucose at various concentrations of glucose in brain and plasma ranging from hypoglycemic to hyperglycemic levels have been determined by direct chemical analyses in the brains of conscious rats. The hexose concentrations were measured chemically in freeze-blown brain extracted with ethanol to avoid the degradation of acid-labile products of [14C]DG back to free [14C]DG that has been found to occur with the more commonly used perchloric acid extraction of brain. Corrections were also made for nonphosphorylatable, labeled products of [14C]DG found in the nonacidic fractions of the brain extracts, which were previously included with the assayed [14C]DG, and for the contribution of the hexose contents in the blood in the brain, which was found to be particularly critical for the determination of the glucose distribution space, especially in hypoglycemic states. From the measured contents of the hexoses in brain and plasma, the relationships of the tissue concentrations and distribution spaces of each of the hexoses and of the Λ (i.e., ratio of tissue distribution space of DG to that of glucose) of the DG method to the tissue glucose concentration were derived. The Λ was then quantitatively related to the measured equilibrium ratio for [14C]methylglucose over the full range of brain and plasma glucose levels. By combining these new data with the values for the lumped constant, the factor that converts rate of DG phosphorylation to glucose phosphorylation, previously determined in rats over the same range of plasma glucose levels, the phosphorylation coefficient was calculated and the lumped constant graphed as a function of the measured distribution space in brain for [14C]methylglucose.

scholarly journals Influence of Plasma Glucose Concentration on Lumped Constant of the Deoxyglucose Method: Effects of Hyperglycemia in the Rat

1990 ◽  
Vol 10 (6) ◽  
pp. 765-773 ◽  
Author(s):  
Franz Schuier ◽  
Francesco Orzi ◽  
Sumio Suda ◽  
Giovanni Lucignani ◽  
Charles Kennedy ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Full Range ◽  
Brain Structures ◽  
Plasma Glucose Concentration ◽  
Glucose Levels ◽  
Lumped Constant ◽  
Arterial Plasma ◽  
The Brain ◽  
Deoxyglucose Method

The lumped constant of the deoxyglucose method was determined by the steady-state, model-independent method in the brain of normal conscious rats with arterial plasma glucose concentrations varying from normoglycemia (i.e., 8 m M) to hyperglycemia (i.e., 31 m M). The lumped constant for brain was found to decrease very gradually with increasing arterial plasma glucose concentration from a value of ∼0.45 in the midnor-moglycemic range (i.e., 7–8 m M) to ∼0.38 at 28–31 m M. 3- O-[14C]Methylglucose was used to assess the distribution of glucose within the brain structures in hyperglycemia; the results indicated that the glucose concentration, and therefore also the values for the lumped constant, remain relatively uniform in hyperglycemia with arterial plasma glucose concentrations as high as 34 m M. The values for the lumped constant for rat brain determined in the present studies were combined with those previously determined in this laboratory for hypoglycemia and normoglycemia by the same method to provide a single source for the values for the lumped constant to be used over the full range of arterial plasma glucose concentrations. In several rats the lumped constant for cephalic extracerebral tissues was also evaluated in parallel with those for the brain. The lumped constant for the cephalic extracerebral tissues was found to be about twice that for brain and to be unaffected by changes in arterial plasma glucose levels.

scholarly journals Modeling the Dependence of Hexose Distribution Volumes in Brain on Plasma Glucose Concentration: Implications for Estimation of the Local 2-Deoxyglucose Lumped Constant

1991 ◽  
Vol 11 (2) ◽  
pp. 171-182 ◽  
Author(s):  
James E. Holden ◽  
Kentaro Mori ◽  
Gerald A. Dienel ◽  
Nancy F. Cruz ◽  
Thomas Nelson ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Time Course ◽  
Full Range ◽  
Specific Radioactivity ◽  
Plasma Glucose Concentration ◽  
Glucose Content ◽  
Glucose Levels ◽  
Constant Change ◽  
Lumped Constant

The steady-state distribution volumes of glucose, 3- O-methylglucose, and 2-deoxyglucose (2DG) are known to change as the concentration of glucose in plasma ranges from hypo- to hyperglycemic values. Model estimates of the three distribution volumes were compared with distribution volume values experimentally measured in the brains of conscious rats as the concentration of glucose in plasma was varied from 2 to 28 m M. The dependence on plasma glucose concentration of the 2DG lumped constant, the factor that relates the phosphorylation rate of 2DG to the net rate of glucose utilization at unit specific radioactivity in the plasma, had been determined previously in separate series of experiments. The model was extended to incorporate this dependence of the lumped constant. In the model both the transport and the phosphorylation barriers were assumed to be single and saturable. The values of their respective half-saturation concentrations and the ratio of the two maximum velocities for glucose were assumed to be invariant over the entire range of plasma glucose concentration. Good agreement between measured and estimated values for the distribution volumes and the lumped constant was attained over the full range of plasma glucose concentration. The model estimates reflected the progressive transport limitation of the brain glucose content as plasma glucose levels were reduced to hypoglycemic values. The results also indicated that these changes should be evident in the time course of 2DG in brain following administration by bolus or continuous infusion, and thus that indexes of local lumped constant change could be derived from the time course data.

scholarly journals Direct Chemical Measurement of the λ of the Lumped Constant of the [14C]Deoxyglucose Method in Rat Brain: Effects of Arterial Plasma Glucose Level on the Distribution Spaces of [14C]Deoxyglucose and Glucose and on λ

1989 ◽  
Vol 9 (3) ◽  
pp. 304-314 ◽  
Author(s):  
Kentaro Mori ◽  
Nancy Cruz ◽  
Gerald Dienel ◽  
Thomas Nelson ◽  
Louis Sokoloff
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Severe Hypoglycemia ◽  
Plasma Glucose Concentration ◽  
Operational Equation ◽  
Chemical Measurements ◽  
Lumped Constant ◽  
Dg Method ◽  
Arterial Plasma ◽  
Distribution Spaces

The lumped constant in the operational equation of the 2-[14C]deoxyglucose (DG) method contains the factor λ that represents the ratio of the steady-state tissue distribution spaces for [14C]DG and glucose. The lumped constant has been shown to vary with arterial plasma glucose concentration. Predictions based mainly on theoretical grounds have suggested that disproportionate changes in the distribution spaces for [14C]DG and glucose and in the value of λ are responsible for these variations in the lumped constant. The influence of arterial plasma glucose concentration on the distribution spaces for DG and glucose and on λ were, therefore, determined in the present studies by direct chemical measurements. The brain was maintained in steady states of delivery and metabolism of DG and glucose by programmed intravenous infusions of both hexoses designed to produce and maintain constant arterial concentrations. Hexose concentrations were assayed in acid extracts of arterial plasma and freeze-blown brain. Graded hyperglycemia up to 28 m M produced progressive decreases in the distribution spaces of both hexoses from their normoglycemic values (e.g., ∼ – 20% for glucose and – 50% for DG at 28 m M). In contrast, graded hypoglycemia progressively reduced the distribution space for glucose and increased the space for [14C]DG. The values for λ were comparatively stable in normoglycemic and hyperglycemic conditions but rose sharply (e.g., as much as 9–10-fold at 2 m M) in severe hypoglycemia.

scholarly journals Brain Glucose Levels in Portacaval-Shunted Rats with Chronic, Moderate Hyperammonemia: Implications for Determination of Local Cerebral Glucose Utilization

1994 ◽  
Vol 14 (1) ◽  
pp. 113-124 ◽  
Author(s):  
Nancy F. Cruz ◽  
Gerald A. Dienel
Keyword(s):  
Glucose Utilization ◽  
Normal Values ◽  
Brain Structures ◽  
Glucose Content ◽  
Brain Glucose ◽  
Glucose Levels ◽  
Lumped Constant ◽  
Dg Method ◽  
The Brain

Rates of glucose utilization (lCMRglc) in many structures of the brain of fed, portacaval-shunted rats, when assayed with the [14C]deoxyglucose (DG) method in our laboratory, were previously found to be unchanged (30 of 36 structures) or depressed (6 structures) during the first 4 weeks after shunting, but to rise progressively to higher than normal values in 25 of 36 structures from 4–12 weeks. In contrast, lCMRglc, when assayed with the [14C]glucose method in another laboratory, was depressed in most structures of brains of 4–8-week shunted rats that had relatively high brain ammonia levels. There was a possibility that the increases in lCMRglc obtained with the [14C]DG method may have been artifactual, due, in part, to a change in brain glucose content which could alter the value of the lumped constant of the DG method. Brain glucose levels of shunted rats were, therefore, assayed by both direct chemical measurement in freeze-blown samples and by determination of steady-state brain:plasma distribution ratios for [14C]methylglucose; the methylglucose distribution ratio varies as a function of plasma and tissue glucose contents. Within a week after shunting, ammonia levels in blood and brain rose to 0.25–0.30 m M and 0.35–0.70 μmol/g, respectively, and mean plasma glucose levels fell from 9–10 m M to 7.4–8.5 m M, and then remained nearly constant. Brains of fedshunted rats had normal glycogen levels and stable but moderately reduced glucose contents between 1 and 12 weeks (i.e., 1.9–2.2 μmol/g). [14C]Methylglucose distribution ratios were essentially the same as those in controls in 22 brain structures at 2 and 8 weeks after shunting. Because brain glucose levels remained stable from 1 to 12 weeks after shunting, there is no evidence to support the hypothesis that the value of the lumped constant would have changed and caused an artifactual rise in lCMRglc.

scholarly journals Effect of Ischemia and Reperfusion on λ of the Lumped Constant of the [14C]Deoxyglucose Technique

1992 ◽  
Vol 12 (1) ◽  
pp. 70-77 ◽  
Author(s):  
Joel H. Greenberg ◽  
Janos Hamar ◽  
Frank A. Welsh ◽  
Valerie Harris ◽  
Martin Reivich
Keyword(s):  
Cerebral Ischemia ◽  
Glucose Metabolism ◽  
Glucose Concentration ◽  
Focal Cerebral Ischemia ◽  
Ischemia And Reperfusion ◽  
Similar Relationship ◽  
Arterial Blood ◽  
Lumped Constant ◽  
Distribution Spaces ◽  
The Brain

We measured the parameter λ, which is the ratio of the distribution spaces of 2-deoxy-d-glucose (DG) and glucose in the brain, in a model of focal cerebral ischemia in the cat. λ is the parameter in the lumped constant of the [14C]DG technique most susceptible to changes in ischemia. Cats were subjected to occlusion of the middle cerebral artery for a period of 2 h. During the last 60 min of occlusion, [14C]DG was infused in a programmed fashion so as to obtain a stable arterial blood [14C]DG concentration. The brain was funnel-frozen to preserve tissue metabolites and the frozen brain was sampled regionally (4 to 7-mg samples) for local concentrations of glucose, ATP, phosphocreatine (PCr), and lactate. In a separate series of cats, the infusion of [14C]DG was started after 2 h of occlusion and 3 h of recirculation. In both series, λ declined slightly for increased levels of tissue glucose and increased appreciably as tissue glucose decreased. A similar relationship was observed between λ and ATP and PCr, although the correlation was not as clear. Since λ, and hence the lumped constant, increases in ischemia as well as in postischemic tissue, it is important to measure tissue glucose concentration if quantitative values of local cerebral glucose metabolism are desired in this condition.

scholarly journals Influence of Glucose Supply and Demand on Determination of Brain Glucose Content with Labeled Methylglucose

1996 ◽  
Vol 16 (3) ◽  
pp. 439-449 ◽  
Author(s):  
Hajime Nakanishi ◽  
Nancy F. Cruz ◽  
Keiji Adachi ◽  
Louis Sokoloff ◽  
Gerald A. Dienel
Keyword(s):  
Glucose Level ◽  
Distribution Ratio ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Surrounding Tissue ◽  
Metabolic Demand ◽  
Glucose Content ◽  
Brain Glucose ◽  
Glucose Levels

The equilibrium brain/plasma distribution ratio for 3- O-methyl-D-glucose (methylglucose) varies with plasma and tissue glucose contents and can be used to determine local glucose levels in brain. This ratio was previously found to rise as brain glucose concentration fell in response to lowered plasma glucose content. The ratios, however, differed with the same tissue glucose levels in conscious and pentobarbital-sedated rats, suggesting that changes in metabolic demand might alter the quantitative relationship between the methylglucose distribution ratio and brain glucose concentration. To examine this possibility, metabolic rate was varied by focal drug application, and hexose concentrations measured in treated and surrounding tissue. When tissue glucose levels were reduced by raised metabolic demand, methylglucose distribution ratios also fell. When brain glucose levels rose due to reduced consumption, the methylglucose distribution ratio also rose. Thus, in contrast to the inverse relationship between brain/plasma methylglucose ratio and brain glucose concentration when brain glucose content is altered secondarily to changes in plasma glucose level, changes in brain glucose content induced by altered glucose utilization cause the brain glucose level and methylglucose distribution ratio to rise and fall in a direct relationship. Determination of brain glucose content from methylglucose distribution ratios must take into account rates of glucose delivery and consumption.

scholarly journals The Lumped Constant of the Deoxyglucose Method in Hypoglycemia: Effects of Moderate Hypoglycemia on Local Cerebral Glucose Utilization in the Rat

1990 ◽  
Vol 10 (4) ◽  
pp. 499-509 ◽  
Author(s):  
Sumio Suda ◽  
Mami Shinohara ◽  
Makoto Miyaoka ◽  
Giovanni Lucignani ◽  
Charles Kennedy ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Glucose Utilization ◽  
Plasma Glucose Concentration ◽  
Local Cerebral Glucose Utilization ◽  
Cerebral Glucose Utilization ◽  
Lumped Constant ◽  
Arterial Plasma ◽  
The Brain ◽  
Deoxyglucose Method

The applicability of the [14C]deoxyglucose method for measuring local cerebral glucose utilization (lCMRglc) has been extended for use in hypoglycemia by determination of the values of the lumped constant to be used in rats with plasma glucose concentrations ranging from approximately 2 to 6 m M. Lumped constant values were higher in hypoglycemia and declined from a value of 1.2 at the lowest arterial plasma glucose level (1.9 m M) to about 0.48 in normoglycemia. The distribution of glucose, and therefore also of the lumped constant, was found to remain relatively uniform throughout the brain at the lowest plasma glucose levels studied. lCMRglc in moderate, insulin-induced hypoglycemia (mean arterial plasma glucose concentration ± SD of 2.4 ± 0.3 m M) was determined with the appropriate lumped constant corresponding to the animal's plasma glucose concentration and compared with the results obtained in six normoglycemic rats. The weighted average rate of glucose utilization for the brain as a whole was significantly depressed by 14% in the hypoglycemic animals, i.e., 61 μmol/100 g/min in hypoglycemia compared to 71 μmol/100 g/min in the normoglycemic controls ( p < 0.05). lCMRglc was lower in 47 of 49 structures examined but statistically significantly below the rate in normoglycemic rats in only six structures ( p < 0.05) by multiple comparison statistics. Regions within the brainstem were most prominently affected. The greatest reductions, statistically significant or not, occurred in structures in which glucose utilization is normally high, suggesting that glucose delivery and transport to the tissue became rate-limiting first in those structures with the greatest metabolic demands for glucose.

scholarly journals The Consequences of Prior Initiation of Breast Feeding on Blood Glucose Levels in Neonates Born In a Tertiary Care Hospital

2020 ◽  
Vol 8 (2) ◽  
pp. 23-29
Author(s):  
Rizwan-U- Zama ◽  
Ayesha Siddiqa ◽  
A.N. Thobbi ◽  
Tehseen Sajid Mudhol ◽  
R Shruthi
Keyword(s):  
Blood Glucose ◽  
Birth Weight ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Blood Glucose Concentration ◽  
Mode Of Delivery ◽  
Postnatal Life ◽  
Care Hospital ◽  
Glucose Levels ◽  
Blood Glucose Levels

Background: Hypoglycemia is the most common event of failure of metabolic adjustments in the newborn. Changes in maternal and fetal monitoring techniques, administration of glucose-containing solutions during labor, delivery and early feeding in neonates significantly alter blood glucose concentrations during the first week of postnatal life. Subjects and Methods: A total of 90 healthy (60 born by FTND, 30 born by LSCS) term, AGA infants were longitudinally evaluated at birth, at one hour after feeds (post feed), and after 6 hours of life. Plasma glucose was estimated from Heel Prick capillary samples by glucometer method. The influence of mode of delivery, the interval between feeds, sex, birth weight, on blood glucose was analyzed. Results: The way of delivery did not affect the plasma glucose concentration in neonates. There was a substantial increase in blood glucose concentration after the first feed irrespective of their birth weight. It was found that female babies had a higher blood glucose concentration than male babies during our study period. All babies maintained normal blood glucose with the continuation of breastfeeding. Conclusion: Plasma glucose levels are satisfactorily maintained in healthy term infants without resort to pre-lacteal feeds and mode of delivery did not influence plasma glucose. There is no need to check blood glucose levels routinely in an asymptomatic, healthy, term, breastfed infants.

scholarly journals NMR Determination of Intracerebral Glucose Concentration and Transport Kinetics in Rat Brain

1992 ◽  
Vol 12 (3) ◽  
pp. 448-455 ◽  
Author(s):  
Graeme F. Mason ◽  
Kevin L. Behar ◽  
Douglas L. Rothman ◽  
Robert G. Shulman
Keyword(s):  
Steady State ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Goodness Of Fit ◽  
Glucose Consumption ◽  
Plasma Glucose Concentration ◽  
Transport Parameters ◽  
Glucose Levels ◽  
Normal Glucose ◽  
Wet Weight

The concentration of intracerebral glucose as a function of plasma glucose concentration was measured in rats by 13C NMR spectroscopy. Measurements were made in 20–60 min periods during the infusion of [1-13C]d-glucose, when intracerebral and plasma glucose levels were at steady state. Intracerebral glucose was found to vary from 0.7 to 19 μmol g−1 wet weight as the steady-state plasma glucose concentration was varied from 3 to 62 m M. A symmetric Michaelis–Menten model was fit to the brain and plasma glucose data with and without an unsaturable component, yielding the transport parameters Km, Vmax, and Kd. If it is assumed that all transport is saturable ( Kd = 0), then Km = 13.9 ± 2.7 m M and Vmax/ Vgly = 5.8 ± 0.8, where Vgly is the rate of brain glucose consumption. If an unsaturable component of transport is included, the transport parameters are Km = 9.2 ± 4.7 m M, Vmax/ Vgly = 5.3 ± 1.5, and Kd/ Vgly = 0.0088 ± 0.0075 ml μmol−1. It was not possible to distinguish between the cases of Kd = 0 and Kd > 0, because the goodness of fit was similar for both. However, the results in both cases indicate that the unidirectional rate of glucose influx exceeds the glycolytic rate in the basal state by 2.4-fold and as a result should not be rate limiting for normal glucose utilization.

scholarly journals Differential Fasting Plasma Glucose and Ketone Body Levels in GHRKO versus 3xTg-AD Mice: A Potential Contributor to Aging-Related Cognitive Status?

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Chelsea M. Griffith ◽  
Lauren N. Macklin ◽  
Andrzej Bartke ◽  
Peter R. Patrylo
Keyword(s):  
Cognitive Function ◽  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Cognitive Aging ◽  
Ketone Body ◽  
Cognitive Status ◽  
Glucose Levels ◽  
Fasting Plasma ◽  
Model Of Alzheimer’S Disease ◽  
The Brain

Cognitive function declines with age and appears to correlate with decreased cerebral metabolic rate (CMR). Caloric restriction, an antiaging manipulation that extends life-span and can preserve cognitive function, is associated with decreased glucose uptake, decreased lactate levels, and increased ketone body (KB) levels in the brain. Since the majority of brain nutrients come from the periphery, this study examined whether the capacity to regulate peripheral glucose levels and KB production differs in animals with successful cognitive aging (growth hormone receptor knockouts, GHRKOs) versus unsuccessful cognitive aging (the 3xTg-AD mouse model of Alzheimer’s disease). Animals were fasted for 5 hours with their plasma glucose and KB levels subsequently measured. Intriguingly, in GHRKO mice, compared to those in controls, fasting plasma glucose levels were significantly decreased while their KB levels were significantly increased. Conversely, 3xTg-AD mice, compared to controls, exhibited significantly elevated plasma glucose levels and significantly reduced plasma KB levels. Taken together, these results suggest that the capacity to provide the brain with KBs versus glucose throughout an animal’s life could somehow help preserve cognitive function with age, potentially through minimizing overall brain exposure to reactive oxygen species and advanced glycation end products and improving mitochondrial function.

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