The effects of methylprednisolone and diabetes on the turnover of alanine and on the transfer of carbon atoms from alanine to pyruvate and glucose in dogs

1980 ◽  
Vol 58 (7) ◽  
pp. 787-796 ◽  
Author(s):  
G. Hetenyi Jr. ◽  
B. Pagurek ◽  
Elizabeth A. Dittmar ◽  
Catherine Ferrarotto

The turnover rate of glucose, the irreversible disposal rate of alanine, and the transfer of carbon atoms from alanine to glucose were studied with the help of tracer methods in normal, methylprednisolone (MP) treated and pancreatectomized dogs. The incorporation of carbon from alanine into pyruvate was also followed. In comparison with normal dogs, in MP-treated dogs the plasma level of alanine and pyruvate were elevated by a factor of about 3 whereas the level of plasma glucose was increased by 10%. Both the turnover rate of glucose and the irreversible disposal rate of alanine were significantly higher. In pancreatectomized dogs plasma alanine and pyruvate levels were not different from normal. There was no increase in the irreversible disposal rate of alanine. Glucose turnover was about twice as much as in normals. The transfer of C atoms from alanine to glucose was increased in both MP-treated and pancreatectomized dogs. The increase was in direct proportion to the increase in the irreversible disposal rate of alanine in MP-treated dogs whereas in pancreatectomized dogs it was due to an increased fraction of the irreversible disposal rate of alanine being converted to circulating glucose. Thus two different mechanisms are responsible for the increased carbon transfer and hence presumably gluconeogenesis in MP-treated and in pancreatectomized animals. The role of insulin as the determinant of the preferred route to increase gluconeogenesis is discussed.

1970 ◽  
Vol 48 (2) ◽  
pp. 115-122 ◽  
Author(s):  
N. Forbath ◽  
G. Hetenyi Jr.

Uniformly labelled 14C-glucose infusions were given to normal and pancreatectomized dogs. Plasma glucose and lactate specific activities were measured by appropriate methods. In normal dogs 14–28% of plasma lactate was found to originate from circulating glucose, and in diabetic dogs 11–18%. This fraction was markedly increased in normal but not significantly so in diabetic dogs during a 2-h infusion of a 6.7–11 mg/kg min glucose load. Uniformly labelled 14C-L(+)-lactate and glucose-6-3H were infused simultaneously for 5 h in normal and pancreatectomized dogs. The glucose turnover rate and incorporation of lactate carbon into glucose were calculated. Of the utilized lactate carbon, 41–49% was incorporated into plasma glucose. The recycling rate of glucose carbon via lactate was estimated to be 3–8% of the glucose turnover rate in the normal dog in the postabsorptive state. The absolute rate of gluconeogenesis from lactate was found to be increased in diabetes.


1980 ◽  
Vol 239 (1) ◽  
pp. E39-E44
Author(s):  
G. Hetenyi ◽  
R. A. Layberry ◽  
D. M. Foster ◽  
M. Berman

The rates of transfer of carbon atoms (mg C . kg body wt-1 . min-1) among plasma glucose, alanine, and lactate have been calculated in pancreatectomized dogs from the tracer concentration versus time curves in the plasma after an intravenous injection of either [2,3-3H]- and [U-14C]alanine or [3-3H]- and [U-14C]glucose. The calculations were based on an integrated kinetic model derived earlier from experimental data. In comparison to normal dogs, in insulin-deprived pancreatectomized dogs, the rate of turnover of glucose (mg C . kg-1 . min-1) is increased about twofold, but the turnover rates of lactate and alanine are not changed significantly. About twice as much carbon is transferred from lactate to glucose, whereas the transfer of carbon from alanine is increased by 47%. Carbon transfer to glucose from unidentified sources is also doubled. In conclusion, in the pancreatectomized dog, gluconeogenesis is increased not by an increased production of alanine and lactate but by an increased diversion of their carbon atoms to glucose at the expense of other pathways.


2014 ◽  
Vol 54 (10) ◽  
pp. 1728 ◽  
Author(s):  
M. Al-Mamun ◽  
Y. Sako ◽  
H. Sano

Isotopic dilution methodology of [U-13C]glucose and [1-13C]Na-acetate were performed simultaneously as primed continuous infusions to determine plasma glucose and acetate metabolism in sheep during thermoneutral (TN) and cold exposure (CE, 2−4°C). The experiment was performed using crossbred (Corriedale × Suffolk) sheep (n = 5; 3 male and 2 female; ~2 years old, 38 ± 2.5 kg of initial bodyweight). The animals were offered mixed hay of orchardgrass and reed canarygrass (40 : 60) 62 g/kg0.75/day with ad libitum water access. Concentration of plasma glucose was determined enzymatically using the glucose oxidase method. Plasma concentration of non-esterified fatty acids (NEFA) and glucose were higher (P = 0.01 and P = 0.05 respectively) during CE than TN. Plasma concentration and the turnover rate of acetate were numerically higher (P = 0.09 and P = 0.25 respectively) during CE than during TN. Plasma glucose turnover rate was higher (P = 0.02) during CE than TN. The present findings suggested that plasma acetate turnover rate tended to be elevated during CE, with further more extensive studies required to clarify the significance.


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.


1975 ◽  
Vol 38 (2) ◽  
pp. 236-240 ◽  
Author(s):  
P. Paul ◽  
M. Donohue ◽  
W. L. Holmes

Uniformly labeled (14C)glucose was infused iv at a constant rate into unanesthetized surgically thyroidectomized (THY) and normal dogs during the basal state at 22 degrees C and during cold exposure at 4–5 degrees C. 02 uptake, CO2 output, and plasma glucose levels were determined; from these rates of glucose turnover and oxidation were calculated. Comparison of THY with normal dogs shows that at a mean plasma glucose level of 103 mg/100 ml, a significantly lower glucose turnover rate was observed in THY dogs on the basis of a kg body weight, body surface area (m-2), but not per cal BMR. The same percentage of glucose turnover was immediately oxidized in THY and normal dogs, accounting for 16 and 15% of the total caloric expenditure, respectively. Acute cold exposure increased energy expenditure in both THY and normal dogs without a change in glucose level or turnover rate. However, the percentage of glucose turnover which was immediately oxidized as well as the amount of glucose oxidized increased significantly and proportionally to the increase in energy expenditure so that the percent of calories derived from plasma glucose oxidation remained the same as that observed during the control period.


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.


Diabetes ◽  
1986 ◽  
Vol 35 (2) ◽  
pp. 186-191 ◽  
Author(s):  
I. Hansen ◽  
R. Firth ◽  
M. Haymond ◽  
P. Cryer ◽  
R. Rizza

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.


1996 ◽  
Vol 270 (4) ◽  
pp. E709-E717 ◽  
Author(s):  
J. A. Tayek ◽  
J. Katz

Eight normal controls and nine non-insulin-dependent diabetes mellitus diabetics were, after an overnight fast, infused for 3 h with [6-3H]- and with [U-13C]glucose with six 13C carbons at rates from 0.03 to 0.15 mg.kg-1.min-1. Plasma glucose and lactate were assayed by gas chromatography-mass spectroscopy. Several parameters of glucose metabolism were calculated from the mass isotopomer distribution. Glucose production (GP) determined with [6-3H]- and [U-13C]glucose agreed closely. GP was 1.9 +/- 0.16 (range 1.3-2.5) mg.kg-1.min-1 in controls and 2.8 +/- 0.29 (1.7-4.5) mg.kg-1.min-1 in diabetics (P < 0.05). The correlation in diabetes between plasma glucose and GP (r = 0.911, P < 0.01) was close. Recycling of carbon (8 vs 7%) dilution by unlabeled carbon (2- vs 2.3-fold), and dilution via the tricarboxylic acid cycle (1.5-fold) were similar in controls and diabetics. Gluconeogenesis was 0.90 +/- 0.08 (0.5-1.3) mg.kg-1.min-1 in controls and 1.30 +/- 0.13 (0.8-1.9) mg.kg-1.min-1 in diabetics (P < 0.05). Gluconeogenesis contributions to GP were 46.6 +/- 4.0% (26-61%) in the controls and 48.8 +/- 5.7% (32-83%) in diabetics. We show that, using [U-13C]glucose infusion of 2-5% of glucose turnover (0.03-0.10 mg.kg-1.min-1), a large number of parameters of glucose metabolism may be determined in humans.


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