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 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 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.

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.

Local cerebral glucose utilization in fetal and neonatal sheep

1984 ◽  
Vol 246 (4) ◽  
pp. R608-R618 ◽  
Author(s):  
R. M. Abrams ◽  
M. Ito ◽  
J. E. Frisinger ◽  
C. S. Patlak ◽  
K. D. Pettigrew ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Glucose Utilization ◽  
Average Rate ◽  
Sensory Stimulation ◽  
Mammalian Brain ◽  
Local Cerebral Glucose Utilization ◽  
Cerebral Energy Metabolism ◽  
Cerebral Glucose Utilization ◽  
The Brain ◽  
Deoxyglucose Method

The newborn mammalian brain of several species has been shown to have a lower average rate of energy metabolism and a narrower range of rates in its various components than is found in maturity. In a further study of cerebral energy metabolism during development, we have employed the [14C]deoxyglucose method for measuring local cerebral glucose utilization in fetal and neonatal sheep. After establishing the lumped constant to be 0.40 and finding the rate constants for the kinetic behavior of deoxyglucose in plasma and brain to be close to those in other species, we measured the rates of glucose utilization in 44 regions of the brain. The rates were low and homogeneous in midgestation, except for those of brain stem nuclei of the auditory and vestibular systems and those of the hippocampus which were relatively high. In the last 7 wk, local rates rose approximately threefold. After birth there was a further average increase of 50% above full-term levels. The study shows that cerebral energy metabolism rises in most structures during prenatal maturation, a time when sensory stimulation is at a relatively low level and behavioral responses are minimal.

scholarly journals Effects of Insulin on Local Cerebral Glucose Utilization in the Rat

1987 ◽  
Vol 7 (3) ◽  
pp. 309-314 ◽  
Author(s):  
Giovanni Lucignani ◽  
Hiroki Namba ◽  
Astrid Nehlig ◽  
Linda J. Porrino ◽  
Charles Kennedy ◽  
...  
Keyword(s):  
Steady State ◽  
Glucose Utilization ◽  
Average Rate ◽  
Experimental Period ◽  
Ventromedial Nucleus ◽  
Local Cerebral Glucose Utilization ◽  
Cerebral Glucose Utilization ◽  
Hypothalamic Nuclei ◽  
The Brain ◽  
Deoxyglucose Method

The effects of hyperinsulinemia on local cerebral glucose utilization were studied by the quantitative autoradiographic 2-[14C]deoxyglucose method in normal conscious rats under steady-state normoglycemic conditions. Hyperinsulinemia and a steady state of normoglycemia were achieved and maintained during the experimental period by a continuous intravenous (i.v.) infusion of insulin given simultaneously with a programmed i.v. infusion of D-glucose. Hyperinsulinemia under normoglycemic conditions did not change the average rate of glucose utilization in the brain as a whole, but significant increases in local glucose utilization were found selectively in the ventromedial, dorsomedial, and anterior hypothalamic nuclei. The results suggest that a known anatomical pathway linking the dorsomedial and anterior nuclei with the ventromedial nucleus of the hypothalamus may be physiologically activated in response to hyperinsulinemia.

scholarly journals Effect of Nitrous Oxide on Local Cerebral Glucose Utilization in Rats

1982 ◽  
Vol 2 (4) ◽  
pp. 481-486 ◽  
Author(s):  
Martin Ingvar ◽  
B. K. Siesjö
Keyword(s):  
Nitrous Oxide ◽  
Glucose Utilization ◽  
Red Nucleus ◽  
Brain Structures ◽  
Subcortical Structures ◽  
Local Cerebral Glucose Utilization ◽  
Cerebral Glucose Utilization ◽  
Spontaneously Breathing ◽  
The Brain ◽  
Deoxyglucose Method

The influence of 70–80% N2O on local local cerebral glucose utilization (CMRg1) in the rat brain was studied with the [14C]deoxyglucose method in minimally restrained, spontaneously breathing animals 75 min following discontinuation of halothane anaesthesia. Nitrous oxide was found to have only small effects on local CMRg1 in the majority of the 25 structures analyzed. When corrections were made for a small difference in body temperature between nitrous oxide–breathing animals and those breathing air, nitrous oxide was found to significantly increase local CMRg1 in some subcortical structures by 15–25% (red nucleus, thalamus, geniculate bodies, and superior colliculus), and to decrease local CMRg1 in nucleus accumbens and sensorimotor cortex by comparable amounts. Thus, although nitrous oxide does not alter overall glucose utilization in the brain, it differentially affects CMRg1 in some brain structures.

Contribution of cortisol to glucose counterregulation in humans

1989 ◽  
Vol 257 (1) ◽  
pp. E35-E42 ◽  
Author(s):  
P. De Feo ◽  
G. Perriello ◽  
E. Torlone ◽  
M. M. Ventura ◽  
C. Fanelli ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Glucose Utilization ◽  
Hepatic Glucose Production ◽  
Hormone Secretion ◽  
Glucose Production ◽  
Plasma Free Fatty Acid ◽  
Normal Subjects ◽  
Plasma Glucose Concentration ◽  
Cortisol Increase

To test the hypothesis that cortisol secretion plays a counterregulatory role in hypoglycemia in humans, four studies were performed in eight normal subjects. In all studies, insulin (15 mU.m-2.min-1) was infused subcutaneously (plasma insulin 27 +/- 1 microU/ml). In study 1, plasma glucose concentration and glucose fluxes [( 3-3H]glucose), substrate, and counterregulatory hormone concentrations were simply monitored, and plasma glucose decreased from 89 +/- 2 to 52 +/- 2 mg/dl for 12 h. In study 2, (pituitary-adrenal-pancreatic clamp), insulin and counterregulatory hormone secretion (except for catecholamines) was prevented by somatostatin (0.5 mg/h, iv) and metyrapone (0.5 g/4 h, per os), and glucagon, cortisol, and growth hormone were infused to reproduce the concentrations of study 1. In study 3 (lack of cortisol increase), the pituitary-adrenal-pancreatic clamp was performed with maintenance of plasma cortisol at basal levels, and glucose was infused, whenever needed, to reproduce plasma glucose concentration of study 2. Study 4 was identical to study 3, but exogenous glucose was not infused. Isolated lack of cortisol increase caused a approximately 22% decrease in hepatic glucose production (P less than 0.01) and a approximately 15% increase in peripheral glucose utilization (P less than 0.01), which resulted in greater hypoglycemia (37 +/- 2 vs. 52 +/- 2 mg/dl, P less than 0.01) despite compensatory increases in plasma epinephrine. Lack of cortisol response also reduced plasma free fatty acid, beta-hydroxybutyrate, and glycerol concentrations approximately 50%. We conclude that cortisol normally plays an important counterregulatory role during hypoglycemia by augmenting glucose production, decreasing glucose utilization, and accelerating lipolysis.

Effect of Halothane Anesthesia on Glucose Utilization and Production in Adolescents 

1995 ◽  
Vol 82 (5) ◽  
pp. 1154-1159 ◽  
Author(s):  
Dounia Sbai ◽  
Philippe Jouvet ◽  
Anne Soulier ◽  
Luc Penicaud ◽  
Jacques Merckx ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Glucose Utilization ◽  
Blood Glucose Concentration ◽  
Glucose Infusion ◽  
Plasma Glucose Concentration ◽  
Whole Body ◽  
Metabolic Clearance ◽  
Halothane Anesthesia ◽  
Plasma Insulin Concentration

Background It should be possible to avoid variations in plasma glucose concentration during anesthesia by adjusting glucose infusion rate to whole-body glucose uptake. To study this hypothesis, we measured glucose utilization and production, before and during halothane anesthesia. Methods After an overnight fast, six adolescents between 12 and 17 yr of age were infused with tracer doses of [6,6-2H2]glucose for 2 h before undergoing anesthesia, and the infusion was continued after induction, until the beginning of surgery. Plasma glucose concentration was monitored throughout, and free fatty acids, lactate, insulin, and glucagon concentrations were measured before and during anesthesia. Results Despite the use of a glucose-free maintenance solution, plasma glucose concentration increased slightly but significantly 5 min after induction (5.3 +/- 0.4 vs. 4.5 +/- 0.4 mmol.l-1, P &lt; 0.05). This early increase corresponded to a significant increase in endogenous glucose production over basal conditions (4.1 +/- 0.4 vs. 3.6 +/- 0.2 mg.kg-1.min-1, P &lt; 0.05), with no concomitant change in peripheral glucose utilization. Fifteen minutes after induction, both glucose utilization and production rates decreased steadily and were 20% less than basal values by 35 min after induction (2.9 +/- 0.3 vs. 3.6 +/- 0.2 mg.kg-1.min-1, P &lt; 0.05). Similarly, glucose metabolic clearance rate decreased by 25% after 35 min. Despite the increase in blood glucose concentration, anesthesia resulted in a significant decrease in plasma insulin concentration. Conclusions These data suggest that halothane anesthesia per se affects glucose metabolism. The decrease in peripheral glucose utilization and metabolic clearance rates and the blunted insulin release question the relevance of glucose infusion in these clinical settings.

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 The Deoxyglucose Method in the Ferret Brain. I. Methodological Considerations

1989 ◽  
Vol 9 (1) ◽  
pp. 35-42 ◽  
Author(s):  
C. Redies ◽  
M. Diksic
Keyword(s):  
Glucose Utilization ◽  
Order Kinetic ◽  
Tracer Injection ◽  
Rate Limiting Step ◽  
Constant Determination ◽  
Lumped Constant ◽  
Methodological Considerations ◽  
Rate Limiting ◽  
The Brain ◽  
Deoxyglucose Method

In the brain of the anesthetized ferret, the 2-deoxyglucose (2-DG) transfer rate constants required to determine cerebral glucose utilization by the deoxyglucose method were calculated from regional gray matter time-radioactivity curves measured for 180 min after tracer injection. Results suggest that loss of metabolized tracer from brain occurs at a rate of about 1%/min for the first 180 min after injection if the rate constant of the rate-limiting step for loss of metabolized tracer ( k*4) represents a first-order kinetic process. A simulation experiment shows that, whether k*4 is assumed to be 0 or 0.01 min−1, has a negligible influence on glucose utilization rates obtained in conventional 45 min autoradiographic experiments provided that the entire analysis, including lumped constant determination, is carried out in a consistent way. The 2-DG lumped constant for k*4 = 0 is 0.54, and 0.68 for k*4 = 0.01 min−1.

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