Total Body-Glucose Turnover in Normal and Intra-Uterine Growth-Retarded Neonatal Piglets

1981 ◽  
Vol 60 (3) ◽  
pp. 335-338 ◽  
Author(s):  
P. A. Flecknell ◽  
R. Wootton ◽  
Muriel John

1. Because studies of the metabolic problems of the human intra-uterine growth-retarded neonate are limited by ethical considerations we have used the intra-uterine growth-retarded piglet as an animal model. Total body-glucose kinetics were measured in 16 intra-uterine growth-retarded and 11 normal piglets from the same litters with [3H]glucose as a tracer. 2. The intra-uterine growth-retarded animals had marginally smaller brains than their normal littermates, but substantially smaller livers. Liver weight was reduced in proportion to body weight. 3. Total body-glucose turnover rate was significantly lower (P < 0.001) in the intra-uterine growth-retarded animals in comparison with their normal littermates, but was appropriate for their smaller body and liver weights. Brain weight was only slightly reduced in the intra-uterine growth-retarded group so that glucose turnover adjusted to a common brain weight was significantly lower (P < 0.001) in these animals. 4. Total body-glucose pool size was lower in the intra-uterine growth-retarded animals (P < 0.01), but was appropriate for their body and liver weights. It was significantly reduced in relation to brain weight (P < 0.001). 5. Resting plasma glucose concentration was lower in the intra-uterine growth-retarded animals (P < 0.001). There was no relationship between concentration and turnover in either group. 6. It is suggested that the observed differences in total body-glucose turnover may be associated with profound differences in cerebral metabolism in the intra-uterine growth-retarded animals.

1983 ◽  
Vol 64 (2) ◽  
pp. 161-165 ◽  
Author(s):  
P. A. Flecknell ◽  
R. Wootton ◽  
Muriel John

1. Cerebral blood flow and cerebral metabolism were measured in conscious, normally grown neonatal piglets and in littermates which had undergone intrauterine growth retardation. 2. Cerebral blood flow was measured by the Kety-Schmidt technique using [125I]iodoantipyrine as the tracer. The tissue: blood partition coefficient of this tracer was measured in separate groups of growth retarded and normal animals. Cerebral utilization rates of glucose and oxygen were calculated from the arteriovenous concentration differences on the Fick principle. 3. The mean body weight of the growth retarded animals was about half that of their normally grown littermates, and liver weight was reduced in proportion. Brain weight was slightly but significantly lower in the growth retarded animals. 4. Cerebral blood flow was lower in the growth retarded piglets but the rates of cerebral utilization of oxygen and glucose were not significantly different in the two groups. The fractional extraction of arterial oxygen by the brain was significantly higher in the growth retarded animals. 5. The partition coefficient of ipdoantipyrine was significantly lower in the growth retarded animals, being about 75% of the normal value. It is clear that had the partition coefficients been assumed to have been the same in both groups the calculated cerebral blood flows would have been identical. 6. It is concluded that growth retarded neonatal piglets have relatively normal sized brains, with a rate of glucose and oxygen consumption that is not significantly different from normal, despite a reduction in cerebral blood flow of about 35%. Consequently the fractional extraction rate of arterial oxygen by the brain is increased from 50% to 70%.


1980 ◽  
Vol 44 (2) ◽  
pp. 193-203 ◽  
Author(s):  
P. A. Flecknell ◽  
R. Wootton ◽  
Muriel John

1. Neonatal hypoglycaemia is a relatively common clinical problem in children but ethical constraints limit the investigations that may be made in the newborn.2. As a preliminary step to assess the suitability of the piglet as a model for glucose metabolism in man, whole-body glucose turnover and glucose pool size were measured using [2-3H]glucose in forty piglets from ten litters.3. Glucose pool size was linearly related to brain weight. However, multiple regression showed that the most useful predictors of pool size were body-weight and resting plasma glucose concentration.4. Glucose turnover was related to both brain weight and body-weight alone, but multiple regression showed that better predictors of turnover were liver weight, spleen weight and pancreas weight.5. Similarities between our own results in piglets and those obtained in human neonates by Bier et al. (1977) extend not only to glucose turnover, but also to its relationship with body-and brain weight. These findings suggest that the piglet may be a useful model for the study of glucose metabolism in babies.


1981 ◽  
Vol 59 (10) ◽  
pp. 1069-1072 ◽  
Author(s):  
P. A. Flecknell ◽  
R. Wootton ◽  
Muriel John ◽  
J. P. Royston

Steady state glucose kinetics were measured in 19 premature and 16 full-term piglets. Bodyweight, plasma glucose concentration, total body glucose turnover rate, and glucose pool size were not significantly different between the two groups. This suggests that the premature piglet is capable of maintaining glucose homeostasis during the first 24 h of life. Although there appeared to be a correlation between glucose turnover and plasma glucose concentration, analysis of covariance showed that it was spurious, suggesting that glucose utilization proceeds independently of the glucose concentration in plasma.Glucose turnover rate in the premature piglet is closely comparable with that reported in the premature human infant. These findings encourage the use of the neonatal piglet as an animal model for the study of the problems of the neonatal human.


1988 ◽  
Vol 255 (6) ◽  
pp. E871-E874
Author(s):  
F. Jahoor ◽  
S. Klein ◽  
H. Miyoshi ◽  
R. R. Wolfe

The importance of the location of isotope infusion and blood sampling on calculating glucose kinetics was studied in five mongrel dogs in the basal state and when glucose turnover was increased during a hyperinsulinemic euglycemic clamp. [U-14C]glucose was infused into the pulmonary artery, unlabeled glucose was infused into a femoral vein to maintain euglycemia, and blood was sampled from the right atrium (AV mode) and the femoral artery (VA mode). In the basal state there was no difference between the AV or VA mode in plateau specific activity; hence, the calculated rate of appearance of glucose was the same with either mode. During the euglycemic clamp procedure, plateau specific activity of the AV mode was significantly lower than that of the VA mode (P less than 0.05). The rate of appearance of glucose calculated from the VA mode was almost identical to the rate of infusion of unlabeled glucose (13.0 +/- 1.4 vs. 12.6 +/- 1.4 mg.kg-1.min-1, respectively), but the rate of appearance of glucose calculated from the AV mode was 12% greater. This study demonstrates that the calculation of glucose kinetics is sensitive to differences in sampling site when the turnover rate is high relative to the mass flow rate (cardiac output times substrate concentration).


1977 ◽  
Vol 233 (2) ◽  
pp. E80
Author(s):  
R R Wolfe ◽  
J F Burke

The simultaneous primed-constant infusion of [6-3H]- and [U-14C]glucose was used to determine the effect of burn injury on glucose turnover, oxidation, and recycling in guinea pigs. Eleven burned animals survived more than 72 h (survivors), whereas five died between 60 and 72 h postburn. All of the controls (n = 9) survived more than 72 h. At 48 h postburn, glucose turnover in the burned survivors was elevated 40% above that in control animals. A greater portion of the burned survivors' turnover was due to recycling and less was directed towards oxidation. The nonsurvivors had both a significantly depressed rate of appearance of glucose and an increased glucose clearance rate. Consequently, they were profoundly hypoglycemic and had a low rate of glucose oxidation. The alterations in glucose kinetics and oxidation apparent after burn did not reflect an inability of burned animals to oxidize exogenously infused glucose, however, because of 2-h infusion of 55 mumol/kg-min of unlabeled glucose doubled glucose oxidation in the burned survivors and tripled it in the nonsurvivors.


1985 ◽  
Vol 54 (2) ◽  
pp. 449-458 ◽  
Author(s):  
A. N. Janes ◽  
T. E. C. Weekes ◽  
D. G. Armstrong

1. Sheep fitted with re-entrant canulas in the proximal duodenum and terminal ileum were used to determine the amount of α-glucoside entering, and apparently disappearing from, the small intestine when either dried-grass or ground maize-based diets were fed. The fate of any α-glucoside entering the small intestine was studied by comparing the net disappearance of such a-glucoside from the small intestine with the absorption of glucose into the mesenteric venous blood.2. Glucose absorption from the small intestine was measured in sheep equipped with catheters in the mesenteric vein and carotid artery. A continuous infusion of [6-3H]glucose was used to determine glucose utilization by the mesenteric-drained viscera and the whole-body glucose turnover rate (GTR).3. The amounts of α-glucoside entering the small intestine when the dried-grass and maize-based diets were given were 13.9 (SE 1.5) and 95.4 (SE 16.2) g/24 h respectively; apparent digestibilities of such α-glucoside in the small intestine were 60 and 90% respectively.4. The net absorption of glucose into the mesenteric venous blood was —2.03 (SE 1.20) and 19.28 (SE 0.75) mmol/h for the dried-grass and maize-based diets respectively. Similarly, total glucose absorption amounted to 1.52 (SE 1.35) and 23.33 (SE 1.86) mmol/h (equivalent to 7 and 101 g/24 h respectively). These values represented 83 and 11 1% of the a-glucoside apparently disappearing from the small intestine, determined using the re-entrant cannulated sheep.5. Total glucose absorption represented 8 and 61% of the whole-body GTR for the dried-grass and maize-based diets respectively. Endogenous glucose production was significantly lower when the sheep were fed on the maize-based diet compared with the dried-grass diet.6. The mesenteric-drained viscera metabolized a small amount of glucose, equivalent to 234 and 17% of the total glucose absorbed for the dried-grass and maize-based diets respectively.7. It is concluded that a large proportion of the starch entering the small intestine of sheep given a maize-based diet is digested and absorbed as glucose, and thus contributes to the whole-body GTR.


2019 ◽  
Vol 244 (16) ◽  
pp. 1430-1437 ◽  
Author(s):  
Jean F Bationo ◽  
Augustin N Zeba ◽  
Nadine D Coulibaly ◽  
Jesse Sheftel ◽  
Christopher R Davis ◽  
...  

Vitamin A status assessment is not straightforward. Retinol isotope dilution (RID) testing requires time for the tracer dose to mix with the total body stores of vitamin A (TBS). Researchers are interested in shortening the time interval between tracer administration and follow-up blood draws, and in re-examining current assumptions about liver mass for calculation of total liver vitamin A reserves (TLR, in µmol/g liver). Schoolchildren (aged 7–12 years; n = 72) were recruited from one school in Burkina Faso. After a baseline blood draw, 1.0 µmol [14,15]-13C2-retinyl acetate was administered to estimate TBS and TLR by retinol isotope dilution with follow-up blood samples at days 7 and 14. Correlations were determined to evaluate if sampling at day 7 could be used to predict TLR compared with day 14. Liver mass was estimated using body surface area and compared with the currently used assumption of liver weight equivalent to 3% of body weight. (This trial was registered at Pan African Clinical Trial Registry: PACTR201702001947398). Liver mass calculated using body surface area did not differ from the standard assumption of 3% of body weight and yielded similar TLR values. The children in this study had mean TLR (0.67 ± 0.35 µmol/g) in the adequate range, while serum retinol concentrations (0.92 ± 0.33 µmol/L) predicted 25% vitamin A deficiency. TLR values at seven days were highly correlated with, but significantly different from day 14 ( P <  0.0001, r =  0.85) and needed a correction factor added to the equation to yield equivalency. Blood drawing at day 7, using correction factors in the prediction equation and the current assumption of liver mass as 3% of body weight, can be used to estimate TLR in schoolchildren with adequate vitamin A status in 13 C2-RID applications, but further investigations are needed to verify the seven-day predictive equation. Impact statement Biomarkers of vitamin A status that reflect the gold standard, i.e. liver biopsy, are available but undergoing refinement to increase accessibility in community-based applications. Retinol isotope dilution testing is one such biomarker. Researchers are interested in decreasing the length of time between isotope administration and follow-up blood draws. This study compared a 7-day blood draw with a 14-day sample. With the simple addition of a correction factor to the prediction equation, the values for total body vitamin A stores were similar, but variation increased with increasing liver reserves. The assumption of 3% of body weight as liver weight in school-aged children was also investigated and confirmed as appropriate in the calculation for total liver vitamin A reserves. Simplifying isotope dilution for population evaluation and building capacity for mass spectrometry analyses are important areas of nutrition development to inform public health programs.


2002 ◽  
Vol 87 (6) ◽  
pp. 543-553 ◽  
Author(s):  
Robert E. Olson ◽  
Jean Chao ◽  
Donna Graham ◽  
Margaret W. Bates ◽  
Jessica H. Lewis

The aims of this study were to determine the total body phylloquinone and its metabolic turnover in human subjects using a tracer dose of [5-H3]phylloquinone containing 55·5×104MBq/mmol. Seven subjects aged 22 to 49 years were given 0·3 μg isotopic phylloquinone intravenously on a control diet (75 μg phylloquinone/d) and blood, urine and faeces were sampled periodically for 6 d. Five of these subjects were studied a second time after 3–8 weeks on a low-vitamin K diet (8 μg/d). The changes in the radioactivity of plasma phylloquinone with time were analysed by the method of residuals and fitted to a curve composed of two exponential components. The size of the exchangeable body pool was calculated by isotope dilution. Plasma phylloquinone levels fell during vitamin K restriction but the vitamin K-dependent coagulation factors did not change. After injection the first exponential decay curvet1/2was 1·0 (SD 0·47) H IN THE SUBJECTS ON THE CONTROL DIET AND 0·49 (sd 0·27) h after vitamin K restriction. On the control diet, the second exponentialt1/2was 27·6 (sd 124) h that did not change on the low-vitamin K diet (t1/2=25·1 (sd 13·5) h). These results indicate that the turnover time for phylloquinone in human subjects is about 1·5 d. Urinary excretion of3H-metabolites ranged from 30 % of the administered dose on the control diet to 38 % on the restricted diet and had the same turnover rate as the second component of the plasma decay curves. The exchangeable body pool of phylloquinone declined from about 1·0 μg/kg before restriction to lower values after vitamin K restriction. The faecal excretion of phylloquinone and its metabolites fell from 32 % of the administered dose on the control diet to 13 % on the restricted diet.


1965 ◽  
Vol 20 (6) ◽  
pp. 1289-1293 ◽  
Author(s):  
Eldred G. Zobl ◽  
Frederick N. Talmers ◽  
Raymond C. Christensen ◽  
Lesem J. Baer

Cerebral hemodynamics and metabolism were studied in 13 normal patients and 14 hypertensive patients at rest and during vigorous physical exercise. Cerebral blood flow was determined by the nitrous oxide method. The cerebral vascular resistance in normal and hypertensive patients remained remarkably constant during exercise despite a marked reduction in total peripheral resistance. Cerebral blood flow was relatively unaffected by the marked increase in cardiac output and the cerebral metabolism did not share in the increased total body metabolism. During vigorous physical exercise the brain behaved as a steady-state organ. cerebral resistance; cerebral blood flow; cerebral oxygen consumption; exercise Submitted on February 4, 1965


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