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 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 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 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.

Glucose lactate interrelations in sheep.

1978 ◽  
Vol 235 (5) ◽  
pp. E487
Author(s):  
P E Reilly ◽  
L G Chandrasena
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Lactate Concentration ◽  
Lactate Production ◽  
Plasma Glucose Concentration ◽  
Constant Infusion ◽  
Dilution Method ◽  
Entry Rate ◽  
Net Production ◽  
Arterial Plasma

The constant-infusion, isotope-dilution method was used to investigate the interrelationships between the glucose and lactate pools of six trained sheep deprived of food overnight. Arterial plasma lactate concentration was a linear function of the net lactate entry rate as was the net production of glucose from lactate, which suggests that the net rate of formation of glucose from lactate is dependent on the availability of lactate. Similarly the arterial plasma glucose concentration was correlated with the net entry rate of glucose as was the net production rate of lactate from glucose, suggesting that the net rate of lactate production from glucose is a function of arterial plasma glucose concentration. The demonstration of these two interrelations between glucose and lactate in normal sheep suggests that, in the absence of external factors producing hormonal or other changes that could cause perturbations of carbohydrate homeostasis, the net rates of conversion of glucose to lactate and of lactate to glucose may be largely determined by the arterial concentrations of glucose and lactate, respectively.

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 Local Cerebral Glucose Utilization in Controlled Graded Levels of Hyperglycemia in the Conscious Rat

1988 ◽  
Vol 8 (3) ◽  
pp. 346-356 ◽  
Author(s):  
F. Orzi ◽  
G. Lucignani ◽  
D. Dow-Edwards ◽  
H. Namba ◽  
A. Nehlig ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Rate Constants ◽  
Glucose Utilization ◽  
Local Cerebral Glucose Utilization ◽  
Glucose Levels ◽  
Cerebral Glucose Utilization ◽  
Glucose Clamp Technique ◽  
Wide Range ◽  
Lumped Constant ◽  
Arterial Plasma

Local cerebral glucose utilization assayed by the [14C]deoxyglucose ([14C]DG) method and calculated by means of its operational equation with values for the rate constants and lumped constant determined in rats under physiological conditions remains relatively stable with variations in arterial plasma glucose concentration within the normoglycemic range. Large changes in arterial plasma glucose level may, however, significantly alter the values of these constants and lead to artifactual results. Values for the lumped constant have been measured and reported for a wide range of arterial plasma glucose concentrations ranging from hypoglycemia to hyperglycemia in the rat (Schuier et al., 1981; Suda et al., 1981; Pettigrew et al., 1983). In the present study we have redetermined the rate constants in rats with arterial plasma glucose levels clamped at ∼350, 450, and 550 mg/dl (i.e., 19, 25, and 31 m M) by a glucose clamp technique. The rate constants for the transport of DG from plasma to brain, K*1, and its phosphorylation in tissue, k*3, were found to decline with increasing plasma glucose levels, while the rate constant for its transport back from brain to plasma, k*2, remained relatively unchanged from its value in normoglycemia. These rate constants were used together with the previously determined values for the lumped constants to calculate local rates of cerebral glucose utilization in three groups of rats in which arterial plasma glucose levels were clamped at ∼350, 450, and 550 mg/dl (i.e., 19, 25, and 31 m M). Average glucose utilization in the brain as a whole was unchanged in hyperglycemia from the values calculated in normoglycemic rats with the standard normal set of constants. Changes in the rate of glucose utilization were found, however, in the hypothalamus, globus pallidus, and amygdala during hyperglycemia.

Lack of relationship between opioid-induced changes in fetal breathing and plasma glucose levels

1995 ◽  
Vol 269 (3) ◽  
pp. R702-R707
Author(s):  
H. H. Szeto ◽  
P. Y. Cheng ◽  
Y. Soong ◽  
D. L. Wu
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Plasma Glucose Concentration ◽  
Glucose Regulation ◽  
Fetal Sheep ◽  
Receptor Selectivity ◽  
Fetal Plasma ◽  
Glucose Levels ◽  
Fetal Breathing ◽  
Induced Changes

The mechanisms by which opioids increase or decrease fetal breathing remain unclear. Fetal plasma glucose is known to modulate breathing activity, and opioids have been reported to alter glucose regulation in the adult. In this study, we investigated whether alterations in fetal breathing by opioids may be explained by changes in plasma glucose levels. We compared the effects of morphine (nonselective), [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO, mu-selective), and [D-Pen2,D-Pen5]enkephalin (DPDPE, delta-selective) on fetal breathing and plasma glucose in unanesthetized fetal sheep. Whereas morphine at 1.2 and 5.0 mg/h iv resulted in an increase in breath number (P < 0.01), plasma glucose was decreased after 1.2 mg/h (P = 0.006) but increased after 5.0 mg/h (P = 0.008). DAMGO (100 micrograms/h icv) increased plasma glucose (P = 0.001) but reduced fetal breathing (P < 0.001). In contrast, DPDPE (30 micrograms/h icv) increased fetal breathing (P = 0.026) but had no effect on plasma glucose concentration. These data demonstrate that the actions of opioids on fetal glucose regulation and breathing are dependent on dose and receptor selectivity. However, there is no relationship between the effects of opioids on fetal breathing and plasma glucose concentration.

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