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J E Cremer

Publications and source records attributed to J E Cremer.

At least 37 records · Page 2Linked to original sources
PubMed1989

Anatomical mapping of glucose transporter protein and pyruvate dehydrogenase in rat brain: an immunogold study.

The regional and cellular distributions of glucose transporter protein (GT) and pyruvate dehydrogenase (PDH) have been studied with an enhanced immunogold method. The results showed significant amounts of GT in neuropil within regions known to exhibit high demands for glucose whilst neuronal perikarya showed little immunostaining. In contrast PDH immunostaining was most intense in neuronal perikarya. The distributions of these proteins were compared and discussed in relation to existing data on local cerebral glucose utilization and the distribution of other important metabolic enzymes. The results suggest that glucose is transported and metabolised in neuropil and that metabolic products such as pyruvate are transported into the neuronal cell body to undergo further metabolism.

Animals↗
PubMed1988

Tracer 2-deoxyglucose kinetics in brain regions of rats given kainic acid.

The initial distribution of tracer amounts of 2-deoxyglucose between plasma and brain tissue, relative to native glucose, and the rate of accumulation of 2-deoxyglucose-6-phosphate were determined in brain regions of rats given kainic acid intravenously. Regional plasma flow was measured in a comparable group of animals. A previously described compartmental model was used to obtain estimates of rates of glucose transport and of glucose phosphorylation. Both rates were significantly increased in entorhinal cortex, hippocampus, amygdala, and septal nucleus. From measured brain tissue and plasma glucose concentrations, glucose fluxes were also calculated in terms of either irreversible or reversible Michaelis-Menten kinetics. In all brain regions of control rats and in six of the ten regions studied in rats given kainic acid, rates of glucose transport calculated in terms of the Michaelis-Menten models were consistent with those estimated by the tracer 2-deoxyglucose procedure. However, in the four regions in which glucose metabolism was stimulated, rates of glucose transport calculated from the behaviour of tracer 2-deoxyglucose were considerably higher than rates calculated from measured concentrations of glucose in plasma and brain tissue using Michaelis-Menten models. The possibility is considered that in those regions that are metabolically stimulated by kainate, there is an increasing asymmetry between the luminal and abluminal membranes of the capillary endothelium in the permeability to glucose and its analogs. An alternative proposal is that in the model used to analyse the tracer 2-deoxyglucose data, the assumption of a rapid mixing of tracer throughout the endogenous pool of tissue glucose prior to phosphorylation becomes invalid. The discrepancies between tracer and native glucose in these particular regions of rats given kainate are consistent with an apparent metabolic compartmentation. The influence of kainate on plasma flow was found to differ regionally, with flow in entorhinal cortex, hippocampus, and amygdala being unchanged. There is some evidence for increased rates of glycolysis relative to oxidative metabolism in these regions.

Animals↗
PubMed1986

Studies on the relationship between cerebral glucose transport and phosphorylation using 2-deoxyglucose.

Regional rates of blood-brain glucose transfer and phosphorylation have been measured in anaesthetized fasted and conscious fed and fasted rats using a dual-label 2-deoxyglucose technique that exploits differences in the early-time distribution of analogue and native glucose between blood and brain. Regional cerebral blood flow was also measured in comparable groups of rats. Estimates of glucose influx in the anaesthetized group were compared with those calculated from previously published kinetic constants obtained using [14C]D-glucose as tracer. The close agreement of these two sets of results served to validate estimates of influx obtained using the glucose analogue. Comparisons between all three groups showed that regional rates of glucose influx were maintained at levels appropriate to the rate of cerebral glucose phosphorylation. This occurred despite wide variations in plasma glucose concentration. The results indicate that at least two factors are involved in the adaptation of glucose supply to meet metabolic demand. One is related to blood flow, and probably reflects changes in the surface area of the capillary endothelium perfused. The second involves changes in the blood-brain barrier permeability to glucose and could reflect changes in the density of functioning glucose transporters within capillary endothelial cell membranes.

Animals↗
PubMed1985

Changes in regional cerebral blood flow and glucose metabolism associated with symptoms of pyrethroid toxicity.

Regional rates of blood flow (rCBF) and of glucose metabolism (rCMRG) were measured in rats showing symptoms typical of an early stage of the type-2 syndrome of pyrethroid toxicity ie. salivation, chewing, and repetitive head and forelimb movements induced by deltamethrin. rCBF was significantly increased in the fourteen brain regions examined, while rCMRG was increased in thirteen of them. In many of the regions the rate of blood flow became excessive in relation to the rate of glucose utilization. This was notable in areas of cerebral cortex, caudate putamen and hippocampus. Values for blood flow in the cortical regions were remarkably similar to those found in rats showing symptoms typical of the type-1 syndrome of pyrethroid toxicity ie. tremors and heightened startle response induced with cismethrin. Excessive blood flow in cerebral cortex appears to be intrinsic to pyrethroid intoxication and unrelated to specific motor symptoms. By contrast, in cerebellum increases in both rCMRG and rCBF appear to correlate with motor disturbances. Other than in cerebellum, a significant increase in rCBF was of early onset, occurring in animals showing salivation and chewing as the only symptoms after being given deltamethrin. The very high ratio of rCBF/rCMRG found in many brain regions of rats given synthetic pyrethroid compounds is unusual and unexplained.

Animals↗
PubMed1983

Regional brain blood flow, blood volume, and haematocrit values in the adult rat.

Measurements of red cell volume, plasma volume, and tissue haematocrit (Hct) were made in 14 brain regions in adult rats using 51Cr-tagged red cells and 125I-labeled human serum albumin. The mean large vessel (systemic artery) Hct was 41.8, total body Hct was 35.3, and of the brain regions, the lowest value (septal nucleus) was 25.91 and the highest (visual cortex) was 32.05. The lowest blood volume was 6.29 microliters g-1 (caudate putamen) and the highest was 14.44 microliters g-1 (inferior colliculus). There was a significant difference between regions in both blood volume and tissue blood Hct. When brain regions were ranked in order of blood volume, this did not coincide with the order for blood flow.

Animals↗
PubMed1983

Relationships between extraction and metabolism of glucose, blood flow, and tissue blood volume in regions of rat brain.

Studies were made on the relationships between the rate of glucose metabolism, the transport of glucose between plasma and brain, cerebral blood flow, and blood content. Conscious control rats were compared with rats with intense tremors induced with cismethrin. The influence of plasma glucose concentration was studied by fasting some animals overnight prior to the induction of tremors. Mean plasma glucose was 8.83 mM in controls, 12.57 mM in fed rats with tremors, and 4.94 mM in rats fasted overnight prior to induction of tremors. Of 12 brain regions studied, nine showed an increased rate of glucose utilization in both fed and fasted trembling rats. Cerebellum had the highest percentage increase (200%). Rates of unidirectional glucose influx in fed trembling rats were significantly greater than those in controls in eight regions. In fasted animals, rates were the same as in controls, except in cerebellum, where it was 1.6 times higher. These high rates of glucose influx at low plasma glucose concentrations were indicative of a change in kinetic parameters of glucose transport. Unidirectional glucose influx rates were transformed to estimates of maximal transport rates (Tmax), based on the Michaelis-Menten equation. Average plasma glucose concentrations in regional capillaries (c) were calculated and shown to be maintained at values close to arterial plasma glucose concentrations (Ca), in all brain regions of each group. In trembling rats, Tmax for each brain region was higher than that in controls. In fasted rats with tremors, Tmax was higher in several brain regions than in fed rats. Tmax in cerebellum was 3.37, 4.71, and 7.89 mumol g-1 min-1 in control, fed trembling, and fasted trembling rats, respectively. Blood flow increased significantly in all regions in rats with tremors and was higher in fasted than in fed animals. There was only a weak correlation between blood flow and Tmax. Blood content of several regions increased in rats with tremors, and there was a strong correlation between Tmax and tissue blood volume. Results are consistent with localized regulatory links between blood flow, capillary surface area, and glucose transport in response to metabolic demand and hypoglycaemia. These involve changes in the linear velocity of blood through capillaries and in the extent of capillary recruitment.

Animals↗
PubMed1982

Inhibition, by 2-oxo acids that accumulate in maple-syrup-urine disease, of lactate, pyruvate, and 3-hydroxybutyrate transport across the blood-brain barrier.

Data are presented in support of the transport of (-)-D-3-hydroxybutyrate across the blood-brain barrier (BBB) being a carrier-mediated process. The kinetic parameters in 21-day-old pentobarbital-anaesthetized rats were Vmax 2.0 mumol.g-1.min-1, Km 29 mM, and KD 0.024 ml.g-1.min-1. The value for Vmax was the same as that for L-lactate and pyruvate transport in animals of the same age. The transport of all three substrates was sensitive to inhibition by low concentrations of either 2-oxo-3-methylbutanoate or 2-oxo-4-methylpentanoate, the 2-oxo acids that can accumulate in patients with maple-syrup-urine disease. The Ki values for the 2-oxo acids were severalfold lower than the respective Km values. 2-Oxo-3-phenylpropionate was a poor inhibitor. The relative affinities of the various monocarboxylic acids for the transport system of the BBB distinguished it from similar systems described in brain, heart, and liver mitochondria; human erythrocytes; and Ehrlich ascites-tumour cells.

3-Hydroxybutyric Acid↗
PubMed1981

A method for the simultaneous estimation of regional rates of glucose influx and phosphorylation in rat brain using radiolabeled 2-deoxyglucose.

A procedure is described which allows the simultaneous estimation of the rate of glucose influx from blood to brain and of the rate of glucose phosphorylation in discrete brain regions of the rat. The method is applicable over an experimental period of 5 min and involves sequential i.v. injections of [14C]2-deoxyglucose and [3H]2-deoxyglucose. Arterial blood samples are collected over the experimental period. After 5 min the rat is killed by microwave irradiation to the head and the brain dissected. The data obtained on glucose, 2-deoxyglucose and 2-deoxyglucosephosphate concentrations in plasma and brain are analyzed in terms of a model which relates the kinetics of 2-deoxyglucose uptake and phosphorylation to those of glucose. The model is based on measurements made of the relative rates of unidirectional influx of glucose and 2-deoxyglucose and of their relative fractional rates of phosphorylation.

Animals↗
PubMed1981

A study of the kinetic behaviour of glucose based on simultaneous estimates of influx and phosphorylation in brain regions of rats in different physiological states.

Results from the application of a procedure that allows simultaneous estimation of the rates of glucose transport from blood and of glucose phosphorylation in discrete regions of the brain are given for groups of rats displaying chemically induced motor disturbances. The procedure is based on sequential injections of [14C]- and [3H]-2-deoxyglucose followed a few minutes later by focused microwave irradiation to the head. Control conscious rats were used and rats displaying either whole body tremors, hind-limb rigidity or choreoathetotic movements induced by synthetic pyrethroid compounds. For individual rats estimates of 5 parameters were obtained in up to 16 brain regions. In addition brain tissue and plasma glucose concentrations were determined. The 5 parameters were: (1) rate of total glucose influx from plasma; (2) rate of glucose phosphorylation (equivalent to net influx); (3) rate of glucose efflux; (4) half-life of free glucose in brain; and (5) PS-product expressed as the ratio of the rate of glucose influx to plasma glucose concentration. For each parameter significant differences between regions were found in all groups of animals including conscious controls. The mean values for the somatosensory cortex of control rats were parameter: (1) 2.02 mumol/g/min; (2) 1.11 mumol/g/min; (3) 0.91 mumol/g/min; (4) 0.94 min; and (5) 0.196 ml/g/min. A high correlation was observed between the rate of total glucose influx and the rate of glucose phosphorylation for all brain regions in all groups of rats. This finding is discussed in terms of a synchronized regulatory mechanism on the glucose transport carrier of capillary endothelial cells and on the functional hexokinase Vmax activity within brain cells.

Animals↗
PubMed1979

Effects of some chlorinated sugar derivatives on the hexose transport system of the blood/brain barrier.

The inhibition of D-glucose transport into brain by several hexose analogues has been investigated in adult anaesthetized rats. D-Glucose was transported with apparent Vmax. = 1.22 mumol/g per min, Km = 11.12 mM and Kd = 0.008 ml/g per min. 6-Chloro-6-deoxyglucose was transported with corresponding values of Vmax. = 1.33 mumol/g per min, Km = 5.5 mM and Kd = 0.0155 ml/g per min and inhibited D-glucose transport with apparent Ki = 3.01 mM. 6-Chloro-6-deoxymannose, 6-chloro-6-deoxygalactose and 6-tosyl-6-deoxygalactose also inhibited D-glucose transport, but 6-chloro-6-deoxyfructose was without effect. The results were consistent with a model for glucose transport at the blood/brain interface that involves a hydrophobic site on the transport protein at or near the 6-position of bound glucose.

Animals↗
PubMed1979

Brain metabolism and specific transport at the blood-brain barrier after portocaval anastomosis in the rat.

The rapid metabolism of [1-14C]butyrate and [2-14C]pyruvate in the brain was studied after intracarotid injection in control rats and rats given an end-to-side portocaval anastomosis (PCA). At 10 or 50 sec after injection there was a 40-50% lowering of the total amount of radioactivity in the brain of operated rats for both compounds. The percentage distribution of label in various metabolic fractions, e.g. amino acids, was unaltered by PCA. The results from the metabolic studies focused on an impaired transport of short chain monocarboxylic acids between blood and brain in rats with a PCA. The brain uptake index (BUI) of acetate, butyrate, pyruvate and glucose was determined by rapid intracarotid injection of the 14C test compound plus 3H2O as a reference marker. At 3 weeks after PCA, transport of all 3 monocarboxylic acids into brain was reduced by 40-50%. The reduction in [2-14C]pyruvate uptake was absent at one week, but thereafter, up to 50 weeks after operation, was consistently present. Eadie-Hofstee analysis of influx at varying substrate concentrations indicated a reduction in Vmax values of pyruvate and butyrate uptake without changes in Km. The calculated influx rate of glucose in operated rats was reduced in direct proportion to the lowering of plasma glucose. Portocaval anastomosis in the rat induces selective changes on substrates that are transported across the blood-brain barrier via a facilitated transport process.

Ammonia↗