Metabolic interrelations of glucose and lactate in unanesthetized normal and diabetic dogs

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 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.


1986 ◽  
Vol 251 (1) ◽  
pp. E71-E77 ◽  
Author(s):  
S. C. Denne ◽  
S. C. Kalhan

Total carbohydrate oxidation, plasma glucose oxidation, and glucose carbon recycling were measured in 11 fasting newborns using a constant infusion of D-[U-13C]glucose combined with respiratory calorimetry. The "true" rate of glucose appearance (Ra) was quantified from the enrichment of the nonrecycling tracer species (m + 6), while the "apparent" rate of glucose appearance was quantified from the enrichment of glucose C - 1. The plasma glucose concentration remained constant at approximately 50 mg/dl (2.8 mM) throughout the study. The true rate of glucose production was 5.02 +/- 0.41 mg X kg-1 X min-1, (means +/- SD). Glucose was oxidized at a rate of 2.67 +/- 0.34 mg X kg-1 X min-1 and represented 53% of the glucose turnover. Recycling of glucose carbon represented 36% of the glucose production rate, or 1.87 +/- 0.74 mg X kg-1 X min-1. The oxidation of plasma glucose provided 15.8 +/- 2.0 kcal X kg-1 X day-1, whereas total carbohydrate oxidation (measured by respiratory calorimetry) provided 19.9 +/- 6.6 kcal X kg X day. The data indicate that 1) recycling of glucose carbon accounts for about one-third of glucose production, demonstrating active gluconeogenesis in the fasting newborn; 2) the oxidation of plasma glucose represents only 80% of total carbohydrate oxidation, the remaining 20% possibly representing the local oxidation of tissue glycogen stores; and 3) as the measured rate of glucose oxidation will be insufficient to supply the entire calculated cerebral metabolic requirements, these data suggest that fuels in addition to glucose may be important for cerebral metabolism in the fasting human newborn.


1986 ◽  
Vol 64 (11) ◽  
pp. 1440-1442 ◽  
Author(s):  
B. Lussier ◽  
G. Hetenyi Jr

The concentration of plasma glucose in insulin deprived pancreatectomized dogs was decreased from the basal 385 ± 44 to 65 ± 12 mg/dL by the infusion of 7 mU∙kg−1∙min−1 insulin. During the infusion, the plasma concentration of immunoreactive glucagon (IRG) did not change and hepatic glucose production was decreased. This is in contrast to earlier findings in alloxan diabetic dogs in which plasma IRG decreased in hypoglycaemia. The hypothesis is put forward that, in contrast to pancreatic alpha cells in which the effect of insulin prevails, neither insulin nor a decrease in the ambient concentration of glucose exerts any effect on the secretion of glucagon from extrapancreatic alpha cells.


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.


1988 ◽  
Vol 66 (1) ◽  
pp. 140-145 ◽  
Author(s):  
G. Hetenyi Jr. ◽  
H. Paradis ◽  
J. Kucharczyk

The turnover rate of glucose, the irreversible disposal rate of lactate, and the rate of gluconeogenesis from lactate were calculated by tracer methods in four normal and four alloxan-diabetic dogs under control conditions as well as in chronic, stable metabolic acidosis and alkalosis. Acidosis was produced by feeding dogs 0.8–1 g∙kg−1∙day−1 NH4Clover 1 week, alkalosis was produced by feeding dogs a chloride-free diet and injections of furosemide. Mean plasma pH in the three states were 7.28 ± 0.013, 7.40 ± 0.024, and 7.51 ± 0.015 in normal dogs, and 7.22 ± 0.025,7.42 ± 0.009, and 7.49 ± 0.002 in the diabetic dogs. Respective mean plasma bicarbonate levels were 14.6 ± 0.88, 22.0 ± 0.80, and 32.4 ± 1.88 mequiv. in normal dogs, and 12.3 ± 1.30, 22.6 ± 0.66, and 35.0 ± 1.14 mequiv. in diabetic animals. In normal dogs shifts in acid–base balance had no effect on the level of plasma glucose or the turnover rate of glucose. In diabetic dogs plasma glucose level was significantly elevated by alkalosis. Plasma lactate was positively correlated with plasma pH(r = 0.69, p < 0.01) and was in general higher in diabetic than in normal animals. The increment in concentration was due to a decreased clearance of lactate from the plasma. The irreversible disposal rate was not changed by the acid–base status. Whereas a larger fraction of lactate removed from the plasma appeared in glucose in diabetic animals, this fraction was not changed significantly by shifts in the acid–base status. The glycemic response to i.v. injected 0.05 U/kg insulin was not appreciably altered by the shifts in acid–base status in either normal or diabetic dogs. Stable metabolic acidosis and alkalosis of moderate degree has little effect on glucose and lactate kinetics and gluconeogenesis from lactate in either normal or diabetic dogs.


1983 ◽  
Vol 245 (2) ◽  
pp. E200-E208
Author(s):  
R. W. Stevenson ◽  
H. Orskov ◽  
J. A. Parsons ◽  
K. G. Alberti

The hormonal and metabolic responses to an intraduodenal glucose load (0.5 g/kg) were first determined in eight normal dogs before diabetes (alloxan/streptozotocin) was induced and then comparison made of the responses to the glucose load when normal plasma glucose profiles were recreated by preprogrammed infusion of insulin via the portal or peripheral circulations. Basal intraportal and peripheral insulin infusions at 0.021 +/- 0.001 and 0.022 +/- 0.000 U . kg-1 . h-1, respectively, for 16 h to fasting diabetic dogs normalized peripheral plasma levels of glucose (5.5 +/- 0.3 and 5.6 +/- 0.6 mmol/liter, respectively), immunoreactive insulin (IRI) (11.5 +/- 1.2 and 16.4 +/- 1.6 microU/ml), glucagon (65 +/- 7 and 62 +/- 5 pg/ml), lactate (0.63 +/- 0.04 and 0.54 +/- 0.03 mmol/liter), and alanine (0.236 +/- 0.037 and 0.191 +/- 0.008 mmol/liter). However, peripheral but not intraportal infusion of insulin depressed levels of glycerol, nonesterified fatty acids (NEFA), and 3-hydroxybutyrate (0.074 +/- 0.006 vs. 0.109 +/- 0.013, P less than 0.01; 0.67 +/- 0.04 vs. 0.84 +/- 0.09, P less than 0.05; and 0.018 +/- 0.004 vs. 0.059 +/- 0.015 mmol/liter, P less than 0.01, respectively). With the preprogrammed insulin infusions used to normalize plasma glucose profiles to the intraduodenal glucose load, all hormonal and metabolic responses were normalized during intraportal infusion (IRI, 72.5 +/- 4.2 microU/ml; glucagon, 66 +/- 10 pg/ml; lactate, 1.06 +/- 0.10 mmol/liter; alanine, 0.251 +/- 0.042 mmol/liter; glycerol, 0.043 +/- 0.013 mmol/liter; NEFA, 0.24 +/- 0.03 mmol/liter; and 3-hydroxybutyrate, 0.012 +/- 0.007 mmol/liter) but marked hyperinsulinemia (103.2 +/- 6.1 microU/ml) and depressed glycerol, NEFA, and 3-hydroxybutyrate responses at 2 h (0.056 +/- 0.005, 0.52 +/- 0.10, and 0.019 +/- 0.010 mmol/liter, respectively) resulted during peripheral infusion. Therefore, only the portal route of insulin infusion achieved complete metabolic normalization during glucose loading in diabetic dogs.


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.


1968 ◽  
Vol 46 (3) ◽  
pp. 391-398 ◽  
Author(s):  
G. Hetenyi Jr. ◽  
G. A. Wrenshall

The intravenous infusion of glucose at rates corresponding to 17–79% of the endogenous (hepatic) rate of glucose production decreased the latter in both normal and diabetic dogs. The increase in the rate of the exogenous infusion and the decrease in the rate of endogenous production were found to be positively correlated. The correlation between the change in the rate of glucose disappearance (utilization plus excretion) and the change in the rate of the exogenous infusion was significant in normal but not in diabetic dogs. The infusion of galactose had no effect on endogenous glucose production. Infusions into the cephalic vein or into the carotid artery were equally effective in decreasing endogenous glucose production. It appears that the rate of endogenous (hepatic) glucose production adapts to an exogenous glucose infusion in both normal and diabetic dogs. Such an adaptation in the rate of glucose disappearance (disposal) was observed only in normal but not in pancreatectomized dogs. Thus the role of the release of insulin in such adaptation is to increase the disposal rather than to decrease the rate of the endogenous production of glucose. The specificity of the adaptive mechanism is demonstrated by the ineffectiveness of galactose in altering glucose turnover.


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