scholarly journals Ketone-body metabolism in tumour-bearing rats

1986 ◽  
Vol 233 (2) ◽  
pp. 485-491 ◽  
Author(s):  
A M Rofe ◽  
R Bais ◽  
R A Conyers
Keyword(s):  
Blood Glucose ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Hepatic Glycogen ◽  
Turnover Rates ◽  
Total Blood ◽  
Normal Tissues ◽  
Tumour Bearing ◽  
And Control

During starvation for 72 h, tumour-bearing rats showed accelerated ketonaemia and marked ketonuria. Total blood [ketone bodies] were 8.53 mM and 3.34 mM in tumour-bearing and control (non-tumour-bearing) rats respectively (P less than 0.001). The [3-hydroxybutyrate]/[acetoacetate] ratio was 1.3 in the tumour-bearing rats, compared with 3.2 in the controls at 72 h (P less than 0.001). Blood [glucose] and hepatic [glycogen] were lower at the start of starvation in tumour-bearing rats, whereas plasma [non-esterified fatty acids] were not increased above those in the control rats during starvation. After functional hepatectomy, blood [acetoacetate], but not [3-hydroxybutyrate], decreased rapidly in tumour-bearing rats, whereas both ketone bodies decreased, and at a slower rate, in the control rats. Blood [glucose] decreased more rapidly in the hepatectomized control rats. Hepatocytes prepared from 72 h-starved tumour-bearing and control rats showed similar rates of ketogenesis from palmitate, and the distribution of [1-14C] palmitate between oxidation (ketone bodies and CO2) and esterification was also unaffected by tumour-bearing, as was the rate of gluconeogenesis from lactate. The carcinoma itself showed rapid rates of glycolysis and a poor ability to metabolize ketone bodies in vitro. The results are consistent with the peripheral, normal, tissues in tumour-bearing rats having increased ketone-body and decreased glucose metabolic turnover rates.

scholarly journals Gluconeogenesis in the cow. The effects of a glucocorticoid on hepatic intermediary metabolism

1970 ◽  
Vol 116 (5) ◽  
pp. 865-874 ◽  
Author(s):  
G. D. Baird ◽  
R. J. Heitzman
Keyword(s):  
Blood Glucose ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Tyrosine Aminotransferase ◽  
Aspartate Transaminase ◽  
Blood Concentrations ◽  
Lactating Cows ◽  
Glycolytic Intermediates ◽  
Blood Glucose Concentrations ◽  
Parallel Measurements

1. The hepatic concentrations of the ketone bodies and of metabolites and activities of enzymes involved in gluconeogenesis were measured in healthy lactating and non-lactating cows 48h after administration of Voren, an ester of dexamethasone, and compared with those found in control animals given saline. Parallel measurements were also made of the blood concentrations of several of the metabolites. 2. Blood glucose concentrations were raised in the Voren-treated animals, whereas blood ketone body and free fatty acid concentrations were unaltered. Similarly there was no change in the hepatic concentrations of the ketone bodies. 3. Significant increases were found in the hepatic concentrations of citrate, 2-oxo-glutarate and malate in both groups of animals given Voren. 4. The hepatic concentrations of those glycolytic intermediates that were measured either decreased or did not change after Voren treatment. 5. The enzymes aspartate transaminase and fructose 1,6-diphosphatase were unchanged in activity after Voren administration, whereas phosphopyruvate carboxylase (EC 4.1.1.32) activity was depressed in the lactating group. However, glucose 6-phosphatase, tryptophan oxygenase and tyrosine aminotransferase increased in activity. 6. In several cases those hepatic metabolites that increased in concentration after Voren administration were present in lower concentration in normal lactating cows than in normal non-lactating cows. The same applied mutatis mutandis to those metabolites that were decreased by Voren. 7. These findings are discussed in relation to the use of glucocorticoids in the treatment of bovine ketosis.

scholarly journals Regulation of glucose and ketone-body metabolism in brain of anaesthetized rats

1974 ◽  
Vol 138 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Neil B. Ruderman ◽  
Peter S. Ross ◽  
Michael Berger ◽  
Michael N. Goodman
Keyword(s):  
Glucose Uptake ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Acetyl Coa ◽  
Total Blood ◽  
Diabetic Ketosis ◽  
Pyruvate Oxidation ◽  
Ketone Body Metabolism ◽  
Arteriovenous Difference ◽  
The Brain

1. The effects of starvation and diabetes on brain fuel metabolism were examined by measuring arteriovenous differences for glucose, lactate, acetoacetate and 3-hydroxybutyrate across the brains of anaesthetized fed, starved and diabetic rats. 2. In fed animals glucose represented the sole oxidative fuel of the brain. 3. After 48h of starvation, ketone-body concentrations were about 2mm and ketone-body uptake accounted for 25% of the calculated O2 consumption: the arteriovenous difference for glucose was not diminished, but lactate release was increased, suggesting inhibition of pyruvate oxidation. 4. In severe diabetic ketosis, induced by either streptozotocin or phlorrhizin (total blood ketone bodies >7mm), the uptake of ketone bodies was further increased and accounted for 45% of the brain 's oxidative metabolism, and the arteriovenous difference for glucose was decreased by one-third. The arteriovenous difference for lactate was increased significantly in the phlorrhizin-treated rats. 5. Infusion of 3-hydroxybutyrate into starved rats caused marked increases in the arteriovenous differences for lactate and both ketone bodies. 6. To study the mechanisms of these changes, steady-state concentrations of intermediates and co-factors of the glycolytic pathway were determined in freeze-blown brain. 7. Starved rats had increased concentrations of acetyl-CoA. 8. Rats with diabetic ketosis had increased concentrations of fructose 6-phosphate and decreased concentrations of fructose 1,6-diphosphate, indicating an inhibition of phosphofructokinase. 9. The concentrations of acetyl-CoA, glycogen and citrate, a potent inhibitor of phosphofructokinase, were increased in the streptozotocin-treated rats. 10. The data suggest that cerebral glucose uptake is decreased in diabetic ketoacidosis owing to inhibition of phosphofructokinase as a result of the increase in brain citrate. 11. The inhibition of brain pyruvate oxidation in starvation and diabetes can be related to the accelerated rate of ketone-body metabolism; however, we found no correlation between the decrease in glucose uptake in the diabetic state and the arteriovenous difference for ketone bodies. 12. The data also suggest that the rates of acetoacetate and 3-hydroxybutyrate utilization by brain are governed by their concentrations in plasma. 13. The finding of very low concentrations of acetoacetate and 3-hydroxybutyrate in brain compared with plasma suggests that diffusion across the blood –brain barrier may be the rate-limiting step in their metabolism.

Some Effects of Metabolic Acidosis on Carbohydrate Metabolism in the Rat

1970 ◽  
Vol 39 (3) ◽  
pp. 375-382 ◽  
Author(s):  
G. A. O. Alleyne ◽  
H. S. Fraser ◽  
H. S. Besterman
Keyword(s):  
Metabolic Acidosis ◽  
Blood Glucose ◽  
Muscle Glycogen ◽  
Fasting Blood Glucose ◽  
Liver Glycogen ◽  
Carbohydrate Diet ◽  
And Control ◽  
Peak Blood ◽  
Peak Blood Glucose

1. Metabolic acidosis was induced by feeding ammonium chloride to rats which were maintained on a carbohydrate diet for 48 h. 2. Fasting blood glucose was the same in acidotic and control animals, but there was an increase in liver glycogen in the former. Muscle glycogen was unchanged. 3. In vitro glycogenolysis was the same in liver slices from normal rats when incubated at a range of pH from 6·90 to 7·40. 4. The peak blood glucose in response to intraperitoneal injections of glucagon was the same in control and acidotic rats. The rate of disappearance of glucose was slower in acidotic rats both after the glucagon induced hyperglycaemia and after intravenously injected glucose. 5. Liver phosphorylase, total glycogen synthetase and the I form of this enzyme were unchanged in acidosis. 6. The data are compatible with the hypothesis that in the acidotic rat there is a block in glycolysis—possibly at the phosphofructokinase step.

scholarly journals The effect of tumour-bearing on 2-deoxy[U-14C]glucose uptake in normal and neoplastic tissues in the rat

1988 ◽  
Vol 253 (2) ◽  
pp. 603-606 ◽  
Author(s):  
A M Rofe ◽  
C S Bourgeois ◽  
R Bais ◽  
R A Conyers
Keyword(s):  
Blood Glucose ◽  
Glucose Uptake ◽  
Blood Glucose Concentration ◽  
Tracer Technique ◽  
Normal Tissues ◽  
Tumour Bearing ◽  
Anaesthetized Rats ◽  
The Difference ◽  
Blood Glucose Concentrations ◽  
Neoplastic Tissues

The extent to which normal and neoplastic tissues of the rate take up glucose was assessed by the 2-deoxy[U-14C]glucose tracer technique. Measurements of glucose uptake were made over 40 min in anaesthetized rats under conditions where the blood glucose concentration was constant. In fed tumour-bearing rats, the relative rates of glucose uptake per g wet wt. of tissue were tumour (100), small intestine (72), brain (61), heart (61), spleen (50), lung (42), adipose tissue (11) and muscle (8). Normal tissues of the fed tumour-bearing rats had decreased rates of glucose uptake as compared with the same tissues in fed non-tumour-bearing control rats. Blood glucose concentrations were similar in both groups, but insulin concentrations were decreased in tumour-bearing rats. Starvation decreased the rates of glucose uptake by normal tissues in both control and tumour-bearing rats, but the difference between the fed and starved states was greater in the control rats. Starvation did not decrease glucose uptake by the tumour. On an organ basis, the tumour (12-14% of body wt.) took up 4 times more glucose than did muscle (40% of body wt.).

Hollow Gold Nanoparticals as Biocompatible Radiosensitizer: An In Vitro Proof of Concept Study

2015 ◽  
Vol 32 ◽  
pp. 106-112 ◽  
Author(s):  
Chien Wen Huang ◽  
Vasant Kearney ◽  
Sina Moeendarbari ◽  
Rui Qian Jiang ◽  
Preston Christensen ◽  
...  
Keyword(s):  
Small Animal ◽  
Intratumoral Injection ◽  
Culture Solution ◽  
Proof Of Concept ◽  
Normal Tissues ◽  
Concept Evaluation ◽  
A Cell ◽  
Clonogenic Cell ◽  
And Control

We report in vitro studies on radiotherapy enhancement of hollow gold nanoparticles (HAuNPs), which feature a 50 nm hollow core and a 30 nm thick polycrystalline shell. A clonogenic cell survival assay was used to assess radiation dose enhancement on breast cancer MDA-MB-231 cells. Cells were cultured in a cell culture solution in which pegylated HAuNPs were added. No cytotoxicity of the HAuNPs was observed at the nanoparticle concentration up to 4.25×109 nanoparticles/ml (350 μM Au concentration). A small animal X-ray irradiator and a clinical linear accelerator were used to irradiate HAuNP-treated and control groups. It shows that the radiation damage to the cells is significantly enhanced when the cells are exposed to HAuNPs. This is the first time that AuNPs with diameter larger than 100 nm has been studied for their radiosensitizing effects. In clinical settings, we envision that HAuNPs could be intratumorally injected into tumors, which is more realistic for practical usage of AuNPs as radiosensitizer than passive accumulation in tumors using the enhanced permeability and retention effect or active targeting. Larger particles are favored for the intratumoral injection approach since larger particles tend to be retained in the injection sites, less likely diffusing into surrounding normal tissues. So, this proof-of-concept evaluation shows a promising potential to use HAuNPs as radiation therapy sensitizer for cancers.

scholarly journals Glycogen metabolism in the liver of the neonatal gsd/gsd and control (GSD/GSD) rat

1982 ◽  
Vol 202 (3) ◽  
pp. 623-629 ◽  
Author(s):  
D G Clark ◽  
S D Neville ◽  
M Brinkman ◽  
O H Filsell
Keyword(s):  
Blood Glucose ◽  
Glucose Concentration ◽  
Blood Glucose Concentration ◽  
Glycogen Metabolism ◽  
Hepatic Glycogen ◽  
Living Tissue ◽  
Neonatal Rats ◽  
And Control ◽  
Blood Glucose Concentrations

1. The metabolism of hepatic glycogen, labelled with [6-3H]glucose at day 19.5 of gestation and with 14C from [U-14C]galactose at delivery, was followed for 10 h in food-deprived gsd/gsd and control (GSD/GSD) neonatal rats. 2. In the affected pups glycogen was maintained at 12% (w/w) and there was no loss of incorporated radioactivity. 3. The 3H and 14C in glycogen from the controls were both decreased by 80%, but 14C was removed at 0-5 h and [6-3H]glucose at 5-10 h. 4. Blood glucose concentrations in the unaffected neonatal rats fell from 5.3 mM at 20 min to 1.7 mM after 10 h. In the gsd/gsd pups blood glucose concentration was decreased from 2 mM at birth to 0.3 mM at 2.5 h: it was maintained at 0.8 mM between 5 and 10 h. 5. In neonatal rats that had been dead for 10 h, hepatic glycogen was decreased by 34% in the controls and by 22% in the gsd/gsd pups. These results demonstrate that liver from the affected rats contains glycogenolytic activity, but that it is not expressed in living tissue.

Some effects of fasting on rats fed a choline-deficient diet

1960 ◽  
Vol 198 (2) ◽  
pp. 371-374 ◽  
Author(s):  
E. Douglas Rees ◽  
William W. Winternitz ◽  
William F. Lattanzi
Keyword(s):  
Blood Glucose ◽  
Ketone Bodies ◽  
Blood Glucose Concentration ◽  
Liver Glycogen ◽  
Control Group ◽  
Deficient Diet ◽  
Hepatic Fat ◽  
Blood Ketone Bodies ◽  
Deficient Group

The blood ketone body concentrations of fasted and nonfasted rats fed a diet deficient in choline were determined and found to be similar to the concentrations obtained from a control group fed the same diet supplemented with choline. However, the animals on the choline-deficient diet had an 18–20% greater mean liver mass, and this could account for the failure to demonstrate the depressed level of blood ketone bodies which was anticipated on the basis of previous in vitro studies. Other possible explanations of this discrepancy are discussed. Despite a high hepatic fat content, the choline-deficient group had a normal concentration of liver glycogen. The nonfasting blood glucose concentration of the choline-deficient group (91.5 ± 5 mg %) was lower than that of the control group (102 ± 3 mg %). After 24 hours of fasting, the values were 52 ± 3 mg % and 61 ± 5 mg % for the choline-deficient and control group, respectively. The 72-hour fasting values were 43 ± 2 mg %, and 49 ± 2 mg %, respectively. Data showing the effect of diet composition on ketonemia, liver glycogen and blood glucose are presented and are in accord with previous studies.

scholarly journals Turnover rates of ketone bodies in normal, starved and alloxan-diabetic rats

1968 ◽  
Vol 110 (4) ◽  
pp. 655-661 ◽  
Author(s):  
Margaret W. Bates ◽  
H. A. Krebs ◽  
D. H. Williamson
Keyword(s):  
Ketone Body ◽  
Alloxan Diabetes ◽  
Ketone Bodies ◽  
Diabetic Rats ◽  
Turnover Rates ◽  
Blood Concentrations ◽  
Order Of Magnitude ◽  
The Mean ◽  
Body Production ◽  
Body Concentration

1. Rates of appearance and disappearance of total ketone bodies were determined in normal, starved and alloxan-diabetic rats by measuring specific radioactivities and concentrations of blood acetoacetate and 3-hydroxybutyrate at different times after injection of 3-hydroxy[14C]butyrate. 2. The mean rates of appearance were 1·7, 4·2 and 10·9μmoles/min./100g. body wt. respectively for normal, starved and alloxan-diabetic rats. The rates of disappearance were of the same order of magnitude as the rates of appearance. 3. There was a direct correlation between the rates of appearance and disappearance and the blood concentrations of the ketone bodies. 4. The results indicate that in the rat increased ketone-body production is paralleled by increased ketone-body utilization and that the raised ketone-body concentration in the blood in starvation and alloxan-diabetes is due to a slight imbalance between the rates of production and utilization. 5. The findings are discussed in relation to the concept that ketone bodies can serve as fuels of respiration when the supply of carbohydrate is limited.

Role of liver nerves and adrenal medulla in glucose turnover of running rats

1985 ◽  
Vol 59 (5) ◽  
pp. 1640-1646 ◽  
Author(s):  
B. Sonne ◽  
K. J. Mikines ◽  
E. A. Richter ◽  
N. J. Christensen ◽  
H. Galbo
Keyword(s):  
Glucose Production ◽  
Constant Infusion ◽  
Moderate Intensity ◽  
Glucose Turnover ◽  
Hepatic Glycogen ◽  
Turnover Rates ◽  
Glycogen Depletion ◽  
And Control ◽  
Liver Nerves

Sympathetic control of glucose turnover was studied in rats running 35 min at 21 m X min-1 on the level. The rats were surgically liver denervated, adrenodemedullated, or sham operated. Glucose turnover was measured by primed constant infusion of [3–3H]glucose. At rest, the three groups had identical turnover rates and concentrations of glucose in plasma. During running, glucose production always rose rapidly to steady levels. The increase was not influenced by liver denervation but was halved by adrenodemedullation. Similarly, hepatic glycogen depletion was identical in denervated and control rats but reduced after adrenodemedullation. Early in exercise, glucose uptake rose identically in all groups and, in adrenodemedullated rats, matched glucose production. Accordingly, plasma glucose concentration increased in liver-denervated and control rats but was constant in adrenodemedullated rats. Compensatory changes in hormone or substrate levels explaining the lack of effect of liver denervation were not found. In rats with intact adrenals, the plasma epinephrine concentration was increased after 2.5 min of running. It is concluded that, in rats carrying out exercise of moderate intensity and duration, hepatic glycogenolysis and glucose production are not influenced by the autonomic liver nerves but are enhanced by circulating epinephrine.

scholarly journals Metabolic interactions of dichloroacetate and insulin in experimental diabetic ketoacidosis. Studies on whole animals and after functional hepatectomy

1975 ◽  
Vol 146 (2) ◽  
pp. 447-456 ◽  
Author(s):  
P J Backshear ◽  
P A H Holloway ◽  
K G M M Alberti
Keyword(s):  
Blood Glucose ◽  
Diabetic Ketoacidosis ◽  
Blood Lactate ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Blood Concentrations ◽  
Metabolic Interactions ◽  
Lactate And Pyruvate ◽  
Body Production ◽  
Body Concentration

1. The infusion of sodium dichloroacetate into rats with severe diabetic ketoacidosis over 4h caused a 2mM decrease in blood glucose, and small falls in blood lactate and pyruvate concentrations. Similar findings had been reported in normal rats (Blackshear et al., 1974). In contrast there was a marked decrease in blood ketone-body concentration in the diabetic ketoacidotic rats after dichloroacetate treatment. 2. The infusion of insulin alone rapidly decreased blood glucose and ketone bodies, but caused an increase in blood lactate and pyruvate. 3. Dichloroacetate did not affect the response to insulin of blood glucose and ketone bodies, but abolished the increase of lactate and pyruvate seen after insulin infusion. 4. Neither insulin nor dichloroacetate stimulated glucose disappearance after functional hepatectomy, but both agents decreased the accumulation in blood of lactate, pyruvate and alanine. 5. Dichloroacetate inhibited 3-hydroxybutyrate uptake by the extra-splachnic tissues; insulin reversed this effect. Ketone-body production must have decreased, as hepatic ketone-body content was unchanged by dicholoracetate yet blood concentrations decreased. 6. It was concluded that: (a) dichloroacetate had qualitatively similar effects on glucose metabolism in severely ketotic rats to those observed in non-diabetic starved animals; (b) insulin and dichloroacetate both separately and together, decreased the net release of lactate, pyruvate and alanine from the extra-splachnic tissues, possibly through a similar mechanism; (c) insulin reversed the inhibition of 3-hydroxybutyrate uptake caused by dichloroacetate; (d) dichloroacetate inhibited ketone-body production in severe ketoacidosis.

Sign in / Sign up

Export Citation Format

Share Document