scholarly journals Evaluation of glucose turnover, body mass and recycling with reversible and irreversible tracers

1974 ◽  
Vol 142 (1) ◽  
pp. 161-170 ◽  
Author(s):  
Joseph Katz ◽  
H. Rostami ◽  
Arnold Dunn

1. Methods are presented for the calculation of rates of synthesis or loss, mean transit time and total body pool of compounds from specific-radioactivity curves, without assuming a multicompartmental model and without fitting the data by exponential expressions. The methods apply to the steady state after either single injection or continuous infusion of a labelled compound. 2. The use of irreversible and reversible tracers and the effects of recycling of carbon on the estimations of the parameters of glucose metabolism are discussed. Methods for quantitatively determining recycling of glucose carbon by the use of glucose doubly labelled with 14C and 3H are presented.

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.


1980 ◽  
Vol 186 (1) ◽  
pp. 161-168 ◽  
Author(s):  
A J Wade

1. The glucose metabolism of conscious lean and obese rats of the Zucker strain was studied by using doubly labelled glucose ([6-3H,U-14C]glucose) given by intravenous injection as a single dose. Fed animals were used, allowing the study to be made in conditions favouring active lipogenesis. 2. At any given prior food intake (consumption during preceding 24 h), the irreversible glucose replacement rate, R0, was considerably higher in the growing obese rat (4-6 months old) when both of these variables were scaled in terms of the total body water of the animals. 3. When scaled in a similar way, the minimal mass of glucose (Mmin.) was also larger in the obese rats. The mean transit time, t, through the pool did not differ significantly between the two groups, but there was a tendency for this to be shorter in obese rats. 4. There was no difference in the proportion of 14C (derived from metabolized labelled glucose) that recycled as [14C]-glucose after passing through the pyruvate pool in the two groups of rats if the rate of recycling of radioactivity (Rc) was expressed as a percentage of R0.


1969 ◽  
Vol 114 (2) ◽  
pp. 203-214 ◽  
Author(s):  
R. G. White ◽  
J. W. Steel ◽  
R. A. Leng ◽  
J. R. Luick

1. Comparisons have been made of three isotope-dilution techniques for measuring parameters of glucose metabolism in sheep given their daily ration in 12 equal amounts (i.e. from 07.00 to 18.00hr.) 2. [U−14C]Glucose was used in all experiments. After a single injection the specific radioactivity of plasma glucose was measured at specific times for up to 24hr. Primed infusions were made with various ratios of P, priming injection (nc), to F, infusion rate (nc/min.) (P/F ratios varying from 23:1 to 147:1) and the specific radioactivity of plasma glucose was measured at 60, 120, 150, 180, 210 and 240min. In continuous infusions the specific radioactivity of plasma glucose was followed for 9hr.; a constant specific radioactivity was observed after approximately 180min. 3. A computer programme was used to fit a multi-exponential equation to the log(specific radioactivity)–time curve after a single injection. A second- or third-order exponential equation was found to fit the results. 4. Conventional analyses of all results showed that similar estimates of the irreversible loss of glucose were obtained by using all three techniques. Estimates of glucose pool size and space by using the primed infusion technique were both significantly higher than estimates obtained by the single injection technique. In these experiments total entry rate could only be determined from the single-injection results and a wide variation in estimates was obtained. 5. Comparisons of the specific radioactivity–time relationships after a single injection of [U−14C]glucose in sheep given their ration either once daily or as a proportion at hourly intervals indicated that there were fluctuations in glucose synthesis in the former over the period of the experiment. The multi-exponential curves fitted to these results had larger residual variances than in sheep given food at hourly intervals. All parameters of glucose metabolism estimated were similar under both feeding regimes. 6. A number of methods of analysis are discussed and a model for glucose metabolism in sheep in suggested.


1978 ◽  
Vol 170 (2) ◽  
pp. 337-342 ◽  
Author(s):  
H Osmundsen ◽  
D Billington ◽  
J R Taylor ◽  
H S A Sherratt

1. The kinetics of glucose metabolism were evaluated in rats deprived of food 15-21 h after the administration of hypoglycaemic doses of hypoglycin (100 mg/kg body wt.) by following changes in the specific radioactivities of 14C and 3H in blood glucose after an intravenous dose of [U-14C,2-3H]glucose [Katz, Rostami & Dunn (1974) Biochem. J. 142, 161-170]. 2. During this time, recycling of glucose through the Cori cycle was virtually abolished, the rate of irreversible disposal of glucose and its total body mass were both decreased by about 70%, whereas there was little effect on the mean transit time for glucose. 3. It was concluded that hypoglycaemia is due to inhibition of gluconeogenesis.


1972 ◽  
Vol 127 (3) ◽  
pp. 521-529 ◽  
Author(s):  
Richard G. Vernon ◽  
Deryck G. Walker

1. The specific radioactivity of plasma d-glucose and the incorporation of 14C into plasma l-lactate, liver glycogen and skeletal-muscle glycogen was measured as a function of time after the intraperitoneal injection of d-[6-14C]glucose and d-[6-3H]glucose into newborn, 2-, 10- and 30-day-old rats. 2. The log of the specific radioactivity of both plasma d-[6-14C]- and d-[6-3H]-glucose of the 2-, 10- and 30-day-old rats decreased linearly with time for at least 60min after injection of labelled glucose. The specific radioactivity of both plasma d-[6-14C]- and d-[6-3H]-glucose of the newborn rat remained constant for at least 75min after injection. 3. The glucose turnover rate of the 30-day-old rat was significantly greater than (approximately twice) that of the 2- and 10-day-old rats. The relative size of both the glucose pool and the glucose space decreased with age. Less than 10% of the glucose utilized in the 2-, 10- and 30-day-old rats was recycled via the Cori cycle. 4. The results are discussed in relationship to the availability of dietary glucose and other factors that may influence glucose metabolism in the developing rat.


1981 ◽  
Vol 194 (2) ◽  
pp. 525-540 ◽  
Author(s):  
Fumikazu Okajima ◽  
Maymie Chenoweth ◽  
Robert Rognstad ◽  
Arnold Dunn ◽  
Joseph Katz

1. [2-3H,U-14C]- or [3-3H,U-14C]-Lactate was administered by infusion or bolus injection to overnight-starved rats. Tracer lactate was injected or infused through indwelling cannulas into the aorta and blood was sampled from the vena cava (A–VC mode), or it was administered into the vena cava and sampled from the aorta (V–A mode). Sampling was continued after infusion was terminated to obtain the wash-out curves for the tracer. The activities of lactate, glucose, amino acids and water were followed. 2. The kinetics of labelled lactate in the two modes differed markedly, but the kinetics of labelled glucose were much the same irrespective of mode. 3. The kinetics of 3H-labelled lactate differed markedly from those for [U-14C]lactate. Isotopic steady state was attained in less than 1h of infusion of [3H]lactate but required over 6h for [U-14C]lactate. 4. 3H from [2-3H]lactate labels glucose more extensive than does that from [3-3H]lactate. [3-3H]Lactate also labels plasma amino acids. The distribution of 3H in glucose was determined. 5. Maximal radioactivity in 3HOH in plasma is attained in less than 1min after injection. Near-maximal radioactivity in [14C]glucose and [3H]glucose is attained within 2–3min after injection. 6. The apparent replacement rates for lactate were calculated from the areas under the specific-radioactivity curves or plateau specific radioactivities after primed infusion. Results calculated from bolus injection and infusion agreed closely. The apparent replacement rate for [3H]lactate from the A–VC mode averaged about 16mg/min per kg body wt. and that in the V–A mode about 8.5mg/min per kg body wt. The apparent rates for [14C]lactate (‘rate of irreversible disposal’) were 8mg/min per kg body wt. for the A–VC mode and 5.5mg/min per kg body wt. for the V–A mode. Apparent recycling of lactate carbon was 55–60% according to the A–VC mode and 35% according to the V–A mode. 7. The specific radioactivities of [U-14C]glucose at isotopic steady state were 55% and 45% that of [U-14C]lactate in the A–VC and V–A modes respectively. We calculated, correcting for the dilution of 14C in gluconeogenesis via oxaloacetate, that over 70% of newly synthesized glucose was derived from circulating lactate. 8. Recycling of 3H between lactate and glucose was evaluated. It has no significant effect on the calculation of the replacement rate, but affects considerably the areas under the wash-out curves for both [2-3H]- and [3-3H]-lactate, and calculation of mean transit time and total lactate mass in the body. Corrected for recycling, in the A–VC mode the mean transit time is about 3min, the lactate mass about 50mg/kg body wt. and the lactate space about 65% of body space. The V–A mode yields a mass and lactate space about half those with the A–VC mode. 9. The area under the wash-out curve for [14C]lactate is some 20–30 times that for [3H]lactate, and apparent carbon mass is 400–500mg/kg body wt. and presumably includes the carbon of glucose, pyruvate and amino acids, which are exchanging rapidly with that of lactate.


1972 ◽  
Vol 25 (6) ◽  
pp. 1313 ◽  
Author(s):  
GJ Judson ◽  
RA Leng

Comparisons have been made of [6_3H]-, [3-3H]-, and [2-3H]glucose with [U-14C]glucose for measuring parameters of glucose metabolism in sheep given their daily ration in 24 equal amounts at hourly intervals. The specific radioactivity (R) of plasma glucose was measured at frequent intervals from 0 to 10 hr and 0 to 32 hr after the start of a constant infusion. or single injection, of mixtures of these isotopes respectively.


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).


1961 ◽  
Vol 38 (3) ◽  
pp. 469-472 ◽  
Author(s):  
K. R. Laumas ◽  
J. F. Tait ◽  
S. A. S. Tait

ABSTRACT Reconsideration of the question of the validity of the calculations of the secretion rates from the specificity activity of a urinary metabolite after the single injection of a radioactive hormone has led us to conclude that the basic equations used in a previous theoretical treatment are not generally applicable to the nonisotopic steady state if the radioactive steroid and hormone are introduced into the same compartment. If this is so, in a two compartmental model with metabolism occurring in both pools, it is now shown that the calculation (S = R — τ) is rigorously valid if certain precautions are taken. This is in contrast to the previous treatment which concluded (in certain special circumstances) that the calculation might not be correct. However, if the hormone is secreted in both compartments and the radioactive steroid is injected into only one, then the calculation (S = R — τ) may not be correct in certain circumstances as was previously concluded (Laumas et al. 1961).


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