The Effect of Combined Ischaemia and Acidosis on Lactate Uptake and Gluconeogenesis in the Perfused Rat Liver

1981 ◽  
Vol 60 (5) ◽  
pp. 537-542 ◽  
Author(s):  
R. A. Iles ◽  
R. D. Cohen ◽  
P. G. Baron
Keyword(s):  
Lactic Acid ◽  
Rat Liver ◽  
Hepatic Uptake ◽  
Strenuous Exercise ◽  
Perfused Rat Liver ◽  
Lactate Uptake ◽  
Glucose Output ◽  
Rat Livers

1. Perfused rat livers were subjected to an acid perfusate and varying degrees of ischaemia in an attempt to simulate the conditions of strenuous exercise or shock. 2. Lactate uptake and glucose output from the liver decreased during moderate ischaemia alone and more so when, in addition, the perfusate was made acidic. 3. Hepatic ATP and ADP content increased in the presence of an acid perfusate. 4. It is concluded that both ischaemia and acidosis may contribute to the diminished hepatic uptake of lactic acid in strenuous exercise and shock.

Coordinated regulation of hepatic glycogen formation in perfused rat liver by glucose and lactate

1994 ◽  
Vol 266 (4) ◽  
pp. E583-E591 ◽  
Author(s):  
Z. Zhang ◽  
J. Radziuk
Keyword(s):  
Rat Liver ◽  
Dose Response ◽  
Glycogen Synthesis ◽  
Hepatic Glycogen ◽  
Perfused Rat Liver ◽  
Response Curves ◽  
Liver Preparation ◽  
Lactate Uptake ◽  
Glucose Output ◽  
Glycogen Formation

Lactate has been found to enhance the formation of glycogen from both glucose and lactate as substrate (Z. Zhang and J. Radziuk. Biochem. J. 280: 415–419, 1991). To evaluate the relative importance of its role as substrate and regulatory factor, a dual dose-response evaluation was done by adding variable amounts of glucose and lactate to the medium in a recirculating perfused rat liver preparation. Nine groups of perfusions were performed utilizing three different levels of carbon infusion into the system: 0.25, 1.0, and 2.0 mg/min. These levels of carbon infusion were further subdivided into different relative amounts of glucose and lactate. Lactate uptake by the perfused liver was linearly related with net glucose output, regardless of the glucose concentrations. In contrast to this, the effect of lactate uptake on the rate of glycogen synthesis is saturable. Moreover, the rate of glycogen formation at which this saturation occurs is dependent only on the mean perfusate glucose concentration. The highest amount of glycogen formed in a 2-h period was 50 +/- 7 mg and the lowest 3.4 +/- 0.3 mg. A family of dose-response curves was generated describing this dual dependence of glycogen formation (both direct and gluconeogenetic pathways) on lactate and glucose.

Metabolic effects of acetate in perfused rat liver studies on ketogenesis, glucose output, lactate uptake and lipogenesis

1982 ◽  
Vol 716 (3) ◽  
pp. 290-297 ◽  
Author(s):  
Alan M. Snoswell ◽  
Rodney P. Trimble ◽  
Richard C. Fishlock ◽  
Gerald B. Storer ◽  
David L. Topping
Keyword(s):  
Rat Liver ◽  
Metabolic Effects ◽  
Perfused Rat Liver ◽  
Lactate Uptake ◽  
Glucose Output

The Effect of Adrenaline on Hepatic Lactate Uptake in the Acidotic Partially Ischaemic Rat Liver

1981 ◽  
Vol 60 (5) ◽  
pp. 543-548 ◽  
Author(s):  
R. A. Iles ◽  
R. D. Cohen ◽  
P. G. Baron ◽  
J. A. Smith ◽  
R. M. Henderson
Keyword(s):  
Blood Flow ◽  
Protective Effect ◽  
Rat Liver ◽  
Strenuous Exercise ◽  
Perfused Liver ◽  
Lactate Uptake ◽  
Glucose Output ◽  
Reduced Flow

1. The effect of adrenaline (7 × 10−8 and 7 × 10−7 mol/l) on lactate uptake and glucose output was studied in the perfused liver of starved rats under conditions of reduced flow and acid perfusate. 2. Adrenaline largely prevented the decrease in hepatic lactate uptake which would otherwise occur owing to reduced blood flow and acidosis and may, therefore, have a protective effect in strenuous exercise and shock.

Hepatic uptake of intact glutathione S-conjugate, inhibition by organic anions, and sinusoidal catabolism

1993 ◽  
Vol 265 (3) ◽  
pp. G547-G554
Author(s):  
C. A. Hinchman ◽  
A. T. Truong ◽  
N. Ballatori
Keyword(s):  
Guinea Pig ◽  
Rat Liver ◽  
Marked Decrease ◽  
Hepatic Uptake ◽  
Half Time ◽  
High Concentrations ◽  
Rat Livers ◽  
Dose Dependent ◽  
Uptake And Metabolism ◽  
Guinea Pig Liver

To identify potential mechanisms for hepatic removal of circulating glutathione (GSH) conjugates, uptake and metabolism of S-2,4-dinitrophenylglutathione (DNP-SG) were examined in isolated perfused livers from rat and guinea pig. Guinea pig livers perfused with 5 mumol of DNP-SG in a recirculating system (50 microM initial concn) rapidly cleared the conjugate from the perfusate (half time 3.7 min), whereas clearance was considerably slower in rat liver (half time 35 min). Disappearance of DNP-SG from the perfusate was accompanied by a simultaneous appearance of DNP-SG and its metabolites in bile. Addition of acivicin, an inhibitor of gamma-glutamyltransferase (gamma-GT), to the perfusate resulted in a marked decrease in DNP-SG clearance by guinea pig liver but had no effect in rat liver, suggesting that in the guinea pig this process is largely dependent on sinusoidal gamma-GT activity. However, even in the presence of acivicin, rat and guinea pig livers removed nearly one-half of the administered DNP-SG from the recirculating perfusate over 30 min. High concentrations of DNP-SG were found in bile (up to 3.7 mM), indicating that the liver is capable of transporting the intact conjugate from the circulation. When rat livers were perfused with higher concentrations of DNP-SG (100 and 250 microM), biliary excretion of DNP-SG increased dose dependently, with concentrations in bile reaching 10 mM at the higher dose. This was accompanied by a dose-dependent choleresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Vanadate inhibits glucose output from isolated perfused rat liver

Hepatology ◽  
1991 ◽  
Vol 14 (3) ◽  
pp. 540-544 ◽  
Author(s):  
Rafael Bruck ◽  
Haia Prigozin ◽  
Zipora Krepel ◽  
Paul Rotenberg ◽  
Yoram Shechter ◽  
...  
Keyword(s):  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Glucose Output

Hepatic uptake of hippurate: a multiple-indicator dilution, perfused rat liver study

1998 ◽  
Vol 274 (1) ◽  
pp. G10-G20 ◽  
Author(s):  
Tsutomu Yoshimura ◽  
Andreas J. Schwab ◽  
Lei Tao ◽  
Ford Barker ◽  
K. Sandy Pang
Keyword(s):  
Benzoic Acid ◽  
Rat Liver ◽  
Hepatic Uptake ◽  
Indicator Dilution ◽  
Monocarboxylate Transporter ◽  
Maximal Velocity ◽  
Perfused Rat Liver ◽  
Hepatic Transport ◽  
Multiple Indicator Dilution ◽  
Multiple Indicator

The hepatic transport of hippuric acid (HA), a glycine-conjugated metabolite of benzoic acid that exhibits only modest plasma albumin binding (binding association constant of 2.1 × 103M−1), was studied in the single-pass perfused rat liver (12 ml/min), using the multiple indicator dilution (MID) technique. The venous recovery of [3H]HA on portal venous injection of a MID dose containing a mixture of a set of noneliminated reference indicators and [3H]HA revealed a survival fraction of unity, corroborating the lack of disappearance of bulk HA from plasma. When the outflow recovery was fitted to the barrier-limited model of Goresky et al. (C. A. Goresky, G. G. Bach, and B. E. Nadeau. J. Clin. Invest. 52: 991–1009, 1973), the derived influx ( P in S ) and efflux ( P out S ) permeability-surface area products were found to be dependent on the concentration of HA (1–930 μM); P in S and P out S were ∼3.5 times the plasma flow rate at low HA concentration, but decreased with increasing HA concentration. All values, however, greatly exceeded the expected contribution from passive diffusion, because the equilibrium distribution ratio of chloroform to buffer for HA was extremely low (0.0001 at pH 7.4). The tissue equilibrium partition coefficient ( P in/ P out, or ratio of influx to efflux rate constants, k 1/ k −1) was less than unity and decreased with concentration. The optimized apparent Michaelis-Menten constant and maximal velocity were 182 ± 60 μM and 12 ± 4 nmol ⋅ s−1 ⋅ g−1, respectively, for influx and 390 ± 190 μM and 29 ± 13 nmol ⋅ s−1 ⋅ g−1, respectively, for efflux. In the presence ofl-lactate (20 mM), however, P in S for the uptake of HA (174 ± 3 μM) was reduced. Benzoic acid (10–873 μM) was also effective in reducing hepatic uptake of HA (5.3 ± 0.9 μM). These interactions suggest that MCT2, the monocarboxylate transporter that mediates the hepatic uptake of lactate and other monocarboxylic acids, may be involved in HA transport.

Uptake of bile acids by perfused rat liver

1976 ◽  
Vol 231 (3) ◽  
pp. 734-742 ◽  
Author(s):  
J Reichen ◽  
G Paumgartner
Keyword(s):  
Bile Acids ◽  
Rat Liver ◽  
Chenodeoxycholic Acid ◽  
Competitive Inhibition ◽  
Compartment Model ◽  
Hepatic Uptake ◽  
Perfused Rat Liver ◽  
Multiple Indicator Dilution ◽  
Rapid Injection ◽  
Carrier Mediated Transport

The uptake of 14C-labeled cholic, taurocholic, and chenodeoxycholic acid by the perfused rat liver was studied to characterize the mechanism responsible for hepatic uptake of bile acids. A rapid-injection multiple indicator-dilution technique and the three-compartment model of Goresky were employed. The kinetics of hepatic uptake of the three bile acids could be described by the Michaelis-Menten equation. The maximal uptake velocities (Vmax) were 24.9 +/- 2.2 (mean +/- SD), 20.8 +/- 1.2, 1.2, and 11.4 +/- 0.9 nmol/s-g liver for cholic, taurocholic, and chenodeoxycholic acid, respectively. The corresponding apparent half-saturation constants (Km) were 526 +/- 125, 258 +/- 43, and 236 +/- 48 nmol/g liver. Competitive inhibition could be demonstrated between cholate and taurocholate as well as between cholate and chenodeoxycholate. Substitution of 94% of the Na+ in the perfusion medium decreased the Vmax and the apparent Km of taurocholate uptake by 68 and 55%, respectively. These findings are consistent with the hypothesis that bile acids are taken up into the hepatocyte by Na+-dependent carrier-mediated transport.

The Effect of Simulated Metabolic Acidosis on Intracellular pH and Lactate Metabolism in the Isolated Perfused Rat Liver

1973 ◽  
Vol 45 (4) ◽  
pp. 543-549 ◽  
Author(s):  
M. H. Lloyd ◽  
R. A. Iles ◽  
B. R. Simpson ◽  
J. M. Strunin ◽  
J. M. Layton ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Intracellular Ph ◽  
Rat Liver ◽  
Extracellular Ph ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Lactate Metabolism ◽  
Lactate Output ◽  
Lactate Uptake ◽  
The Relationship

1. The relationship between extracellular pH (pHe), intracellular pH (pHi) and lactate uptake was studied in the isolated perfused rat liver during simulated metabolic acidosis. 2. pHi fell to a considerably less extent than pHe when the latter was decreased from pH 7·4 to 6·7. 3. The liver took up lactate when pHi was greater than 7·0; at lower values of pHi lactate output occurred. 4. The relevance of these observations to the control of hepatic pHi and lactate metabolism is discussed.

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