scholarly journals The rate of gluconeogenesis from various precursors in the perfused rat liver

1967 ◽  
Vol 102 (3) ◽  
pp. 942-951 ◽  
Author(s):  
B. D. Ross ◽  
R. Hems ◽  
H. A Krebs
Keyword(s):  
Amino Acids ◽  
Rat Liver ◽  
Negative Ions ◽  
Perfused Liver ◽  
Perfused Rat Liver ◽  
Optimum Conditions ◽  
Perfusion Medium ◽  
Intermediary Metabolites ◽  
Lactate And Pyruvate ◽  
Sites Of Action

1. The rates of gluconeogenesis from many precursors have been measured in the perfused rat liver and, for comparison, in rat liver slices. All livers were from rats starved for 48hr. Under optimum conditions the rates in perfused liver were three to five times those found under optimum conditions in slices. 2. Rapid gluconeogenesis (rates of above 0.5mumole/g./min.) were found with lactate, pyruvate, alanine, serine, proline, fructose, dihydroxyacetone, sorbitol, xylitol. Unexpectedly other amino acids, notably glutamate and aspartate, and the intermediates of the tricarboxylic acid cycle (with the exception of oxaloacetate), reacted very slowly and were not readily removed from the perfusion medium, presumably because of permeability barriers which prevent the passage of highly charged negative ions. Glutamine and asparagine formed glucose more readily than the corresponding amino acids. 3. Glucagon increased the rate of gluconeogenesis from lactate and pyruvate but not from any other precursor tested. This occurred when the liver was virtually completely depleted of glycogen. Two sites of action of glucagon must therefore be postulated: one concerned with mobilization of liver glycogen, the other with the promotion of gluconeogenesis. Sliced liver did not respond to glucagon. 4. Pyruvate and oxaloacetate formed substantial quantities of lactate on perfusion, which indicates that the reducing power provided in the cytoplasm was in excess of the needs of gluconeogenesis. 5. Values for the content of intermediary metabolites of gluconeogenesis in the perfused liver are reported. The values for most intermediates rose on addition of lactate. 6. The rates of gluconeogenesis from lactate and pyruvate were not affected by wide variations of the lactate/pyruvate ratio in the perfusion medium.

scholarly journals The effect of propionate on the metabolism of pyruvate and lactate in the perfused rat liver

1972 ◽  
Vol 127 (3) ◽  
pp. 539-543 ◽  
Author(s):  
T. M. Chan ◽  
R. A. Freedland
Keyword(s):  
Rat Liver ◽  
Sodium Butyrate ◽  
Perfused Rat Liver ◽  
Pyruvate Metabolism ◽  
Perfusion Medium ◽  
Lactate And Pyruvate ◽  
Sparing Effect

1. Rates of gluconeogenesis in the perfused rat liver from propionate, l-lactate, pyruvate and the combination of propionate with either lactate or pyruvate were measured. Less than additive rates were obtained with either propionate plus lactate or propionate plus pyruvate. 2. The uptake of pyruvate plus lactate from the perfusion medium was decreased more seriously when propionate was present with lactate than with pyruvate. 3. The use of [2-14C]pyruvate in the presence of propionate showed that the decreased disappearance of pyruvate plus lactate did not result in their formation from propionate. 4. The addition of sodium butyrate to the perfusion medium caused an inhibition of gluconeogenesis from propionate and stimulated gluconeogenesis and uptake of pyruvate and lactate. 5. The observations are consistent with there being a sparing effect of propionate on lactate and pyruvate metabolism.

ACTION OF RAT PROLACTIN ON PLASMA SOMATOMEDIN LEVELS IN THE RAT AND ON SOMATOMEDIN RELEASE FROM PERFUSED RAT LIVER

1977 ◽  
Vol 75 (1) ◽  
pp. 137-143 ◽  
Author(s):  
D. J. HILL ◽  
M. J. O. FRANCIS ◽  
R. D. G. MILNER
Keyword(s):  
Rat Liver ◽  
Costal Cartilage ◽  
Perfused Liver ◽  
Perfused Rat Liver ◽  
Perfusion Medium ◽  
Cartilage Metabolism ◽  
Intravenous Injections ◽  
And Cartilage

Rat prolactin at a concentration of 50 ng/ml perfusion medium stimulated the production of somatomedin-like activity (SLA) from the perfused liver of normal rats. The effect was demonstrable in perfusions performed at 11.00 h in which rat prolactin caused a mean (±s.e.m.) increase in the uptake of [35S]sulphate into rat costal cartilage in vitro of 64 ± 14% in comparison with controls, but at 15.00 h no effect was observed. No effect of rat prolactin on hypophysectomized rat liver was detectable at 11.00 h. Hypophysectomized and sham-operated rats were given five intravenous injections of 50 μg rat prolactin or a similar volume of hormone solvent at 12 h intervals. Plasma somatomedin activity (SMA) and cartilage metabolism, measured by the uptake of radioactive sulphate and thymidine by costal cartilage in vitro, were similar in hypophysectomized animals given rat prolactin or hormone solvent. Sham-operated rats given rat prolactin showed a significant increase of plasma SMA and cartilage metabolism compared with control animals. The production of SLA by rat liver in response to rat prolactin may be related to the density of specific hepatic lactogenic receptors, since these are absent or present only in low numbers in hypophysectomized animals.

Cell-swelling-induced taurine release from isolated perfused rat liver

1994 ◽  
Vol 72 (1-2) ◽  
pp. 8-11 ◽  
Author(s):  
H. S. Brand ◽  
A. J. Meijer ◽  
L. A. Gustafson ◽  
G. G. A. Jörning ◽  
A. C. J. Leegwater ◽  
...  
Keyword(s):  
Amino Acids ◽  
Rat Liver ◽  
Cell Swelling ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Liver Mass ◽  
Taurine Release ◽  
Perfusion Medium ◽  
Nacl Concentration ◽  
Isolated Liver

Astrocytes and lymphocytes are able to release significant amounts of taurine during periods of hypotonicity to reduce the increase in cell volume. To investigate this mechanism in the liver, we studied the release of free amino acids from isolated perfused rat liver during hypotonicity. The osmolarity of the perfusion medium was reduced from 305 to 255 or 205 mosM by decreasing the NaCl concentration 25 or 50 mM, respectively. This induced an 6–8% increase in liver mass and was associated with a specific 1.7-fold (−50 mosM) and 14-fold (−100 mosM) increase of the taurine release. None of the other amino acids measured showed a significant increase in their concentration in the effluent. The increase in taurine release occurred within 30 s after exposure to hypotonicity (maximal after 1–1.5 min) and followed closely the changes in liver mass. The taurine release declined gradually during successive exposures of the isolated liver to −100 mosM. This release was 29 and 17% of the original during the second and third exposure, respectively.Key words: cell swelling, liver, taurine.

scholarly journals Metabolism of inorganic sulphate in the isolated perfused rat liver. Effect of sulphate concentration on the rate of sulphation by phenol sulphotransferase

1978 ◽  
Vol 176 (3) ◽  
pp. 959-965 ◽  
Author(s):  
Gerard J. Mulder ◽  
Katja Keulemans
Keyword(s):  
Steady State ◽  
Plasma Concentration ◽  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Perfusion Medium ◽  
Physiological Concentration ◽  
Sulphate Concentration ◽  
Inorganic Sulphate

1. The metabolism of inorganic [35S]sulphate (Na235SO4) was studied in the isolated perfused rat liver at three initial concentrations of inorganic sulphate in the perfusion medium (0, 0.65 and 1.30mm), in relation to sulphation and glucuronidation of a phenolic drug, harmol (7-hydroxy-1-methyl-9H-pyrido[3,4-b]indole). 2. [35S]Sulphate rapidly equilibrated with endogenous sulphate in the liver. It was excreted in bile and reached, at the lowest concentration in the perfusion medium, concentrations in bile that were much higher than those in the perfusion medium; at the higher sulphate concentrations, these concentrations were equal. The physiological concentration of inorganic sulphate in the liver, available for sulphation of drugs, is similar to the plasma concentration. 3. At zero initial inorganic sulphate in the perfusion medium, the rate of sulphation was very low and harmol was mainly glucuronidated. At 0.65mm-sulphate glucuronidation was much decreased and considerable sulphation took place, indicating efficient competition of conjugation by sulphation. At 1.30mm-sulphate the sulphation increased still further. 4. The results suggest that an important factor in sulphation is the relatively high Km of synthesis of adenosine 3′-phosphate 5′-sulphatophosphate (the co-substrate of sulphation) for inorganic sulphate, which is of the order of the plasma concentration of inorganic sulphate. The steady-state adenosine 3′-phosphate 5′-sulphatophosphate concentration may determine the rate of sulphate conjugation of drugs in the rat in vivo.

scholarly journals Accumulation of amino acids by the perfused rat liver in the presence of ethanol

1973 ◽  
Vol 134 (3) ◽  
pp. 697-705 ◽  
Author(s):  
Hans A. Krebs ◽  
Reginald Hems ◽  
Patricia Lund
Keyword(s):  
Amino Acids ◽  
Rat Liver ◽  
Major Effect ◽  
Major Product ◽  
Control Mechanisms ◽  
Perfused Rat Liver ◽  
Carbamoyl Phosphate ◽  
Lactate Formation ◽  
Gluconeogenesis From Alanine ◽  
Almost All

1. The rate of gluconeogenesis from alanine in the perfused rat liver is affected by the presence of other metabolizable substances, especially fatty acids, ornithine and ethanol. Gluconeogenesis is accelerated by oleate and by ornithine. When both oleate and ornithine were present the acceleration was greater than expected on the basis of mere additive effects. 2. Much NH3 and some urea were formed from alanine when no ornithine was added. With ornithine almost all the nitrogen released from alanine appeared as urea. 3. Lactate was a major product of alanine metabolism. Addition of oleate, and especially of oleate plus ornithine, decreased lactate formation. 4. Ethanol had no major effect on gluconeogenesis from alanine when this was the sole added precursor. Gluconeogenesis was strongly inhibited (87%) when oleate was also added, but ethanol greatly accelerated gluconeogenesis when ornithine was added together with alanine. 5. In the absence of ethanol the alanine carbon and alanine nitrogen removed were essentially recovered in the form of glucose, lactate, pyruvate, NH3 and urea. 6. In the presence of ethanol the balance of both alanine carbon and alanine nitrogen showed substantial deficits. These deficits were largely accounted for by the formation of aspartate and glutamine, the formation of which was increased two- to three-fold. 7. When alanine was replaced by lactate plus NH4Cl, ethanol also caused a major accumulation of amino acids, especially of aspartate and alanine. 8. Earlier apparently discrepant results on the effects of ethanol on gluconeogenesis from alanine are explained by the fact that under well defined conditions ethanol can inhibit, or accelerate, or be without major effect on the rate of gluconeogenesis. 9. It is pointed out that in the synthesis of urea through the ornithine cycle half of the nitrogen must be supplied in the form of asparate and half in the form of carbamoyl phosphate. The accumulation of aspartate and other amino acids suggests that ethanol interferes with the control mechanisms which regulate the stoicheiometric formation of aspartate and carbamoyl phosphate.

Biliary excretion of dihydro-11-keto-progesterone-4-C14 by isolated perfused liver

1964 ◽  
Vol 207 (5) ◽  
pp. 1030-1034 ◽  
Author(s):  
G. F. Leong ◽  
D. M. Cazes ◽  
M. L. Berliner ◽  
D. L. Berliner
Keyword(s):  
Rat Liver ◽  
Biliary Excretion ◽  
Half Life ◽  
Water Soluble ◽  
Isolated Perfused Rat Liver ◽  
Perfused Liver ◽  
Rapid Rate ◽  
Perfused Rat Liver ◽  
Bile Formation ◽  
Entire Study

The rates of biliary excretion of dihydro-11-keto-progesterone-4-C14 and of its metabolites were studied in the isolated perfused rat liver. The half-life of this steroid in the perfusing blood was 2.5 min, and at 40 min about 75% of the injected steroid had been excreted in bile. Formation of water-soluble steroids (WS St) took place at a rapid rate and by 60 min 100% of the steroids in blood were found to be water soluble. During the entire study the steroids excreted in bile were water soluble and accounted for 97.2–100% (avg. 98.2%). No dihydro-11-keto-progesterone was found to be excreted in the bile. The rate of disappearance from the blood, excretion in the bile, and degree of formation of WS St of this compound when compared with corticosterone and cortisol shows the following pattern: dihydro-11-keto-progesterone > corticosterone > cortisol.

Utilisation of Amino Acids by the Perfused Rat Liver

1976 ◽  
Vol 20 (6) ◽  
pp. 404-414 ◽  
Author(s):  
D.A. Hems ◽  
M.G. Davies ◽  
A.J. Thomas ◽  
P.D. Whitton
Keyword(s):  
Amino Acids ◽  
Rat Liver ◽  
Perfused Rat Liver
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