scholarly journals Rates of glucose utilization and glucogenesis in rats in the basal state induced by halothane anaesthesia

1977 ◽  
Vol 162 (3) ◽  
pp. 643-651 ◽  
Author(s):  
D F Heath ◽  
K N Frayn ◽  
J G Rose

1. Rates and rate coefficients of glucose utilization and replacement were determined with [5-3H]- and [U-14C]-glucose in rats starved for 24h, either conscious or under halothane anaesthesia, in a thermoneutral environment. Plasma insulin concentrations were also measured. 2. Halothane anaesthesia decreased the turnover rate by 20%, which was similar to previously reported decreases in metabolic rates caused by natural sleep. 3. Fractional recycling of glucose carbon was little affected by halothane. 4. Comparison of values in one rat with those in another, among both conscious rats and those under halothane anaesthesia, showed that rate coefficients were inversely correlated with plasma glucose concentrations. 5. These findings indicated that halothane, in the concentration used (1.25%, v/v), had little specific effect on glucose metabolism. 6. Although equilibrium plasma glucose concentrations in different rats under halothane were widely different (4-8 mmol/l) the rates of utilization were very similar (2.5-3.1 micronmol/min per 100 g), indicating that these rates were determined by the production of glucose from gluconeogenic precursors released by basal metabolism, the rate of which is necessarily similar in different rats. 7. Among rats under halothane anaesthesia plasma insulin concentrations were negatively correlated with rate coefficients, showing that the differences between rate coefficients were mostly accounted for by differences between rats in tissue sensitivities to insulin. Thus in each 24h-starved rat, sleeping or resting, the main regulators of the plasma glucose concentrations were the rate of supply of gluconeogenic substrates from energy metabolism and the intrinsic sensitivity of the tissues to insulin. 8. We found that a commonly used deionization method of purifying glucose for determination of its specific radioactivity was inadequate.

1974 ◽  
Vol 142 (1) ◽  
pp. 171-183 ◽  
Author(s):  
Joseph Katz ◽  
Arnold Dunn ◽  
Maymie Chenoweth ◽  
Sybil Golden

1. Glucose labelled with 3H in position 2 and uniformly with 14C was administered simultaneously to rabbits and rats either as a single injection or by continuous infusion. Plasma glucose specific radioactivity and the yield of 3H in the plasma water were monitored. 2. The rates of synthesis, recycling of carbon and total body mass of glucose were calculated, without assuming a multicompartmental model and without fitting data by exponential expressions. 3. The rate of synthesis of glucose in starved-overnight rabbits was 4mg/min per kg (range 3–4.5mg/min per kg) and 25–35% of the glucose carbon was recycled. The mass of total body glucose in starved rabbits was 290mg/kg (range 220–390mg/kg). About one-third of the total body glucose equilibrates nearly instantaneously with plasma glucose. 4. In rats starved overnight, glucose synthesis was about 10mg/min per kg and recycling of carbon ranged from 30–40%. Total body mass (per kg body weight) is similar to that in rabbits. 5. The activity in plasma water after injection of [2-3H]glucose was determined. The initial rate of 3H2O formation is rapid, indicating that the major site of glucose catabolism is in the rapidly mixing pool. The curve of total body glucose radioactivity was obtained from the 3H2O yield, and total mass of glucose was calculated. This agrees with that obtained from the 3H specific-radioactivity curve.


1977 ◽  
Vol 162 (3) ◽  
pp. 653-657 ◽  
Author(s):  
D F Heath ◽  
K N Frayn ◽  
J G Rose

1. Rates and rate coefficients of glucose utilization and replacement in post-absorptive rats, either conscious or under halothane anaesthesia, were determined in a thermoneutral environment by using [5-3H]- and [U-14C]glucose. Label was not injected into rats under halothane until about 0.5h after anaesthesia was initiated. 2. Comparison with the results for 24h-starved rats in the preceding paper [Heath et al. (1977) Biochem. J. 162, 643-651] showed that insulin concentrations were considerably higher but rate coefficients for glucose utilization were little altered in post-absorptive rats. Sensitivity to insulin was thus considerably increased by a 24h period of starvation in the rat. 3. Fractional recycling of glucose carbon in post-absorptive rats was under one-half of that in starved rats, reflecting the larger contribution of liver glycogenolysis to glucose production in the former. 4. In post-absorptive rats halothane decreased the mean rate of glucose utilization by about 17%. This decrease was associated with an increase in mean plasma insulin concentration, showing that halothane decreased sensitivity to insulin. 5. Recycling was slightly increased by halothane, indicating that the contribution of liver glycogen to the total glucogenic rate was decreased, probably because liver glycogen concentration were about 40% lower throughout the rate determinations in halothane. 6. Comparison of our results with earlier work shows that during and shortly after induction of halothane anaesthesia glucose turnover must have been greatly increased whereas from about 0.5h after induction it was decreased.


1988 ◽  
Vol 255 (6) ◽  
pp. R1035-R1040
Author(s):  
R. Hoo-Paris ◽  
M. L. Jourdan ◽  
L. C. Wang ◽  
R. Rajotte

In hypothermia, impairment of metabolic substrate mobilization and utilization may be a factor limiting survival. By use of a newly developed technique, substrate profiles and their regulation by insulin were examined in hypothermic rats (body temperature 19 degrees C) over 24 h. Plasma glucose concentrations increased to approximately 300 mg/dl during cooling and remained high throughout the period of hypothermia. Free fatty acid (FFA) concentration was not altered during cooling or during the first 10 h of hypothermia (approximately 700 mu eq/l) but progressively decreased thereafter, reaching 420 mu eq/l by 20 h. Plasma insulin decreased dramatically during cooling and remained very low (9 +/- 2 microU/ml) during the whole period of hypothermia, reflecting the suppression of insulin secretion by isolated islets at low temperatures. To test he hypothesis that suppression of endogenous insulin secretion may hamper glucose utilization and thus limit survival in hypothermia, exogenous insulin was administered. At doses of 0.1, 0.5, and 1 U/kg intravenously, insulin slowly decreased plasma glucose and FFA. However, at 0.1 and 1 U/kg intraperitoneally, insulin resulted in a dose-dependent decrease in survival time in the hypothermic rat. It is possible that the antilipolytic effect of insulin may have outweighed any beneficial effect of improving glucose utilization in hypothermia.


1985 ◽  
Vol 248 (4) ◽  
pp. R391-R399 ◽  
Author(s):  
J. Katz

A mitochondrial model of gluconeogenesis and the tricarboxylic acid cycle, where pyruvate is metabolized via pyruvate carboxylase and pyruvate dehydrogenase, and pyruvate kinase is examined. The effect of the rate of tricarboxylic acid flux and the rates of the three reactions of pyruvate metabolism on the labeling patterns from [14C]pyruvate and [24C]acetate are analyzed. Expressions describing the specific radioactivities and 14C distribution in glucose as a function of these rates are derived. Specific radioactivities and isotopic patterns depend markedly on the ratio of the rates of pyruvate carboxylation and decarboxylation to the rate of citrate synthesis, but the effect of phosphoenolpyruvate hydrolysis is minor. The effects of these rates on 1) specific radioactivity of phosphoenolpyruvate, 2) labeling pattern in glucose, and 3) contribution of pyruvate, acetyl-coenzyme A, and CO2 to glucose carbon are illustrated. To determine the contribution of lactate or alanine to gluconeogenesis, experiments with two compounds labeled in different carbons are required. Methods in current use to correct for the dilution of 14C in gluconeogenesis from [14C]pyruvate are shown to be erroneous. The experimental design and techniques to determine gluconeogenesis from 14C-labeled precursors are presented and illustrated with numerical examples.


1988 ◽  
Vol 253 (1) ◽  
pp. 27-32 ◽  
Author(s):  
G Hetenyi ◽  
P J Anderson ◽  
M Raman ◽  
C Ferrarotto

1. Non-anaesthetized normal and diabetic rats were fasted for 1 day, and [U-14C]glycine, or [U-14C]serine, or [U-14C]- plus [3-3H]-glucose was injected intra-arterially. The rates of synthesis de novo/irreversible disposal for glycine, serine and glucose, as well as the contribution of carbon atoms by the amino acids to plasma glucose, were calculated from the integrals of the specific-radioactivity-versus-time curves in plasma. 2. The concentrations of both glycine and serine in blood plasma were lower in diabetic than in fasted normal animals. 3. The rates of synthesis de novo/irreversible disposal of both amino acids tended to be lower in diabetic animals, but the decrease was statistically significant only for serine (14.3 compared with 10.5 mumol/min per kg). 4. Of the carbon atoms of plasma glucose, 2.9% arose from glycine in both fasted normal and diabetic rats, whereas 4.46% of glucose carbon originated from serine in fasted normal and 6.77% in diabetic rats. 5. As judged by their specific radioactivities, plasma serine and glycine exchange carbon atoms rapidly and extensively. 6. It was concluded that the turnover of glycine remains essentially unchanged, whereas that of serine is decreased in diabetic as compared with fasted normal rats. The plasma concentration of both amino acids was lower in diabetic rats. Both glycine and serine are glucogenic. In diabetic rats the contribution of carbon atoms from glycine to glucose increases in direct proportion to the increased glucose turnover, whereas the contribution by serine becomes also proportionally higher.


1976 ◽  
Vol 230 (1) ◽  
pp. 138-142 ◽  
Author(s):  
MS Anwer ◽  
TE Chapman ◽  
R Gronwall

Variables of glucose metabolism determined by the use of [U-14C]glucose were compared in fed and fasted ponies. Relative recycling of glucose carbon with respect to tritium in fed animals was negligible for 6-T and 3-T and 16% for 2-T studies; in fasted animals relative recycling was 12 and 14% for 6-T and 3-T studies, respectively. Minimal mass of total-body glucose decreased significantly in the fasted ponies. Based on relative recycling of carbon to tritium, a negligible fraction of plasma glucose was produced via the Cori cycle or from glycerol in fed ponies; recycled tricarbon units contributed 12% of glucose produciton in ponies fasted 72 h. In fed ponies, 16% of plasma glucose carbon was recycled via a futile cycle at the glucose 6-phosphate stage. Glucose utilization was best estimated with the use of [6-T]glucose (or 3-T).


1981 ◽  
Vol 194 (2) ◽  
pp. 513-524 ◽  
Author(s):  
J Katz ◽  
F Okajima ◽  
M Chenoweth ◽  
A Dunn

L-[3-3H,U-14C]Lactate was administered to starved rats either as a bolus or by continuous infusion. Tracer administration was performed two ways: injection into the vena cava and sampling from the aorta (V-A mode), or injection into the aorta and sampling from the vena cava (A-VC mode). The specific-radioactivity curves after infusion or injection differed markedly with the two procedures. However, the specific radioactivities of 14C-labelled glucose derived from [U-14C]lactate were similar in the two modes. The apparent turnover rates of lactate calculated from the 3H specific-radioactivity curves in the V-A mode were about half those obtained from the 3H specific-radioactivity curves in the A-VC mode. The apparent contribution of lactate carbon to glucose carbon calculated from specific-radioactivity curves of the A-VC mode was greater than that obtained from the V-A mode. The apparent recycling of lactate carbon calculated from the specific radioactivities for [U-14C]- and [3-3H]-lactate was greater in the A-VC mode than the V-A mode. [U-14C] Glucose was administered in the two modes, but in contrast with lactate the specific radioactivities were only slightly different. An analysis to account for these observations is presented. It is shown that the two modes represent sampling from different pools of lactate. The significance of sites of tracer administration and sampling for the interpretation of tracer kinetics of compounds present in intracellular and extracellular spaces, and with a high turnover rate, is discussed. We propose that for such compounds, including lactate, alanine and glycerol, the widely used V-A mode leads to a marked underestimate of replacement, mass and carbon recycling, and that the A-VC mode is the preferred method for the assessment of these parameters.


1972 ◽  
Vol 128 (4) ◽  
pp. 879-899 ◽  
Author(s):  
Joseph Katz ◽  
P. A. Wals

1. Slices of mammary gland of lactating rats were incubated with glucose labelled uniformly with 14C and in positions 1, 2, 3 and 6, and with 3H in all six positions. Glucose carbon atoms are incorporated into CO2, fatty acids, lipid glycerol, the glucose and galactose moieties of lactose, lactate, soluble amino acids and proteins. C-3 of glucose appears in fatty acids. The incorporation of 3H into fatty acids is greatest from [3-3H]glucose. 3H from [5-3H]glucose appears, apart from in lactose, nearly all in water. 2. The specific radioactivity of the galactose moiety of lactose from [1-14C]- and [6-14C]-glucose was less, and that from [2-14C]- and [3-14C]-glucose more, than that of the glucose moiety. There was no randomization of carbon atoms in the glucose moiety, but it was extensive in galactose. 3. The pentose cycle was calculated from 14C yields in CO2 and fatty acids, and from the degradation of galactose from [2-14C]glucose. A method for the quantitative determination of the contribution of the pentose cycle, from incorporation into fatty acids from [3-14C]glucose, is derived. The rate of the reaction catalysed by hexose 6-phosphate isomerase was calculated from the randomization pattern in galactose. 4. Of the utilized glucose, 10–20% is converted into lactose, 20–30% is metabolized via the pentose cycle and the rest is metabolized via the Embden–Meyerhof pathway. About 10–15% of the triose phosphates and pyruvate is derived via the pentose cycle. 5. The pentose cycle is sufficient to provide 80–100% of the NADPH requirement for fatty acid synthesis. 6. The formation of reducing equivalents in the cytoplasm exceeds that required for reductive biosynthesis. About half of the cytoplasmic reducing equivalents are probably transferred into mitochondria. 7. In the Appendix a concise derivation of the randomization of C-1, C-2 and C-3 as a function of the pentose cycle is described.


1969 ◽  
Vol 112 (3) ◽  
pp. 373-377 ◽  
Author(s):  
D. F. Heath ◽  
J. G. Rose

1. Of the glucose in rat blood 79·8±3·3% (s.d.) was in the plasma. The variance was mostly due to differences between rats. 2. The concentration of glucose in erythrocyte water was 51±8% (s.d.) of that in plasma water. 3. The ratio (specific radioactivity in plasma)/(specific radioactivity in whole blood), i.e. the P/B ratio, was estimated for glucose at intervals after intravenous injection of [U−14C]glucose and [U−14C]fructose. The ratio differed from unity by more than the standard error of a single determination of the specific radioactivity of blood or plasma glucose except from 10 to 17min. after injection of [14C]glucose and from 22 to 30min. after injection of [14C]fructose. At all other times specific radioactivities in blood had to be corrected to give specific radioactivities in plasma. How to do so is described. 4. The P/B ratios were accounted for by a turnover of glucose in erythrocytes of 0·14μmole/min./ml. of erythrocytes. 5. Metabolism of glucose in rat erythrocytes is unlikely to be a major source of lactate.


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