scholarly journals Interrelations between ureogenesis and gluconeogenesis in isolated hepatocytes. The role of antion transport and the competition for energy

1978 ◽  
Vol 170 (2) ◽  
pp. 379-385 ◽  
Author(s):  
A B Wojtczak ◽  
E I Wałajtys-Rode ◽  
M J H Geelen

1. Glucose synthesis from lactate plus pyruvate and from lactate plus alanine was measured in the presence or absence of 1mM-oleate or 2mM-octanoate at low (2mM) or high (8mM) concentrations of NH4Cl. 2. Both fatty acids alone or with 2mM-NH4Cl doubled glucose production from lactate plus pyruvate. Glucose synthesis from lactate plus alanine, in the presence of oleate, was decreased 16% by 2mM-NH4Cl. 3. In the presence of fatty acids, 8mM-NH4Cl decreased gluconeogenesis by 60-65% from both lactate plus pyruvate and lactate plus alanine. This inhibition was correlated with a high accumulation of aspartate and a drastic decrease in 2-oxoglutarate and malate in the cells. 4. In the presence of 2mM- or 8 mM-NH4Cl, oleate and glucogenic precursors, the addition of 2.5mM-ornithine stimulated urea synthesis. 5. This was paralleled by a decrease of 16% in glucose synthesis from lactate plus pyruvate in the presence of 2mM-NH4Cl and had no effect at 8mM-NH4Cl. In the system producing glucose from lactate plus alanine, ornithine completely reversed the inhibition caused by 2mM-NH4Cl and only partly that by 8mM-NH4Cl. 6. Gluconeogenesis from pyruvate was also inhibited by 2mM-NH4Cl in the presence of oleate or ethanol. This way due to the decrease of malate, which is the C4 precursor of glucose in this system. 7. The limitation of gluconeogenesis by 2-oxoglutarate and malate concentrations in the liver cell and the competition for energy between glucose and urea synthesis is discussed.

2000 ◽  
Vol 278 (4) ◽  
pp. R956-R963 ◽  
Author(s):  
Jean-Michel Weber ◽  
Deena S. Shanghavi

The rate of hepatic glucose production (Ra glucose) of rainbow trout ( Oncorhynchus mykiss) was measured in vivo by continuous infusion of [6-3H]glucose and in vitro on isolated hepatocytes to examine the role of epinephrine (Epi) in its regulation. By elevating Epi concentration and/or blocking β-adrenoreceptors with propranolol (Prop), our goals were to investigate the mechanism for Epi-induced hyperglycemia to determine the possible role played by basal Epi concentration in maintaining resting Ra glucose and to assess indirect effects of Epi in the intact animal. In vivo infusion of Epi caused hyperglycemia (3.75 ± 0.16 to 8.75 ± 0.54 mM) and a twofold increase in Ra glucose (6.57 ± 0.79 to 13.30 ± 1.78 μmol ⋅ kg− 1 ⋅ min− 1, n = 7), whereas Prop infusion decreased Ra from 7.65 ± 0.92 to 4.10 ± 0.56 μmol ⋅ kg− 1 ⋅ min− 1( n = 10). Isolated hepatocytes increased glucose production when treated with Epi, and this response was abolished in the presence of Prop. We conclude that Epi-induced trout hyperglycemia is entirely caused by an increase in Ra glucose, because the decrease in the rate of glucose disappearance normally seen in mammals does not occur in trout. Basal circulating levels of Epi are involved in maintaining resting Ra glucose. Epi stimulates in vitro glucose production in a dose-dependent manner, and its effects are mainly mediated by β-adrenoreceptors. Isolated trout hepatocytes produce glucose at one-half the basal rate measured in vivo, even when diet, temperature, and body size are standardized, and basal circulating Epi is responsible for part of this discrepancy. The relative increase in Ra glucose after Epi stimulation is similar in vivo and in vitro, suggesting that indirect in vivo effects of Epi, such as changes in hepatic blood flow or in other circulating hormones, do not play an important role in the regulation of glucose production in trout.


1978 ◽  
Vol 172 (2) ◽  
pp. 333-342 ◽  
Author(s):  
Marion Stubbs ◽  
Pierre V. Vignais ◽  
Hans A. Krebs

1. The effects of atractyloside and carboxyatractyloside (between 5 and 40μm) on O2 uptake, glucose synthesis, urea synthesis, the adenine nucleotide content and the intracellular K+ concentration were measured in isolated hepatocytes. 2. Urea synthesis was much less inhibited than glucose synthesis by both atractylosides. Measurements of intermediary metabolites of carbohydrate metabolism in freeze-clamped liver after injection of atractyloside into rats indicate that inhibition of gluconeogenesis is due to interference at the cytosolic reactions requiring ATP (phosphoenolpyruvate carboxykinase and 3-phosphoglycerate kinase). 3. The decrease in [ATP]/[ADP]×[Pi] after addition of atractyloside or carboxyatractyloside was restricted to the cytosol. 4. Dihydroxyacetone can be converted either into glucose with the consumption of 2mol of ATP (per mol of glucose) or into lactate with the production of 2mol of ATP. In the presence of high concentrations of atractyloside and carboxyatractyloside more ATP was produced than was used for the synthesis of glucose from dihydroxyacetone, probably for the maintenance of intracellular [K+]. 5. When the rates of respiration were altered by changing substrates, the degrees of inhibition of respiration and translocation by a given concentration of the atractylosides were the same, whereas at a given concentration of HCN the degree of inhibition was high at higher initial rates, and low at lower initial rates. 6. Inhibition of a complex series of reactions by atractyloside does not necessarily indicate that the translocator is a rate-limiting step in that sequence as Th. P. M. Akerboom, H. Bookelman & J. M. Tager [(1977) FEBS. Lett.74, 50–54] assume. This point is discussed.


1981 ◽  
Vol 200 (2) ◽  
pp. 429-433 ◽  
Author(s):  
P Ferré ◽  
P Satabin ◽  
L El Manoubi ◽  
S Callikan ◽  
J Girard

In hepatocytes from 1-day-old rats, active gluconeogenesis occurs in parallel with active ketogenesis, although the carbon atoms of non-esterified fatty acids do not participate in glucose synthesis. Once a significant ketogenesis is established, a further increase does not enhance gluconeogenesis. Indeed, octanoate is more ketogenic than oleate, but stimulates gluconeogenesis to a similar extent.


Diabetes ◽  
1997 ◽  
Vol 46 (2) ◽  
pp. 187-196 ◽  
Author(s):  
D. K. Sindelar ◽  
C. A. Chu ◽  
M. Rohlie ◽  
D. W. Neal ◽  
L. L. Swift ◽  
...  

1985 ◽  
Vol 230 (2) ◽  
pp. 303-311 ◽  
Author(s):  
R C Scaduto ◽  
E J Davis

The isolated perfused rat kidney was shown to synthesize serine from aspartate or glutamate, both of which are also precursors of glucose. The major products of aspartate metabolism were ammonia, serine, glutamate, glucose, glutamine and CO2. Perfusion of kidneys with aspartate in the presence of amino-oxyacetate resulted in a near-complete inhibition of aspartate metabolism, illustrating the essential role of aspartate aminotransferase in the metabolism of this substrate. Radioactivity from 14C-labelled aspartate and from 14C-labelled glycerol was incorporated into serine and glucose. Production of both glucose and serine from aspartate was suppressed in the presence of 3-mercaptopicolinic acid. These data provide evidence for the operation of the phosphorylated and/or non-phosphorylated pathway for serine production to the presence of 3-mercaptopicolinic acid. This is explained by simultaneous glycolysis. The rate of glucose production, but not that of serine, was greater in kidneys perfused with glutamate or with aspartate plus glycerol than the rates obtained by perfusion with aspartate alone. These data are taken to suggest that serine synthesis occurred at a near-maximal rate, and that the capacity of the kidney for serine synthesis from glucose precursors is lower than that for glucose synthesis.


Diabetes ◽  
1997 ◽  
Vol 46 (2) ◽  
pp. 187-196 ◽  
Author(s):  
D. K. Sindelar ◽  
C. A. Chu ◽  
M. Rohlie ◽  
D. W. Neal ◽  
L. L. Swift ◽  
...  

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1898-P
Author(s):  
ADELINA I.L. LANE ◽  
SAVANNA N. WENINGER ◽  
FRANK DUCA

Diabetes ◽  
1988 ◽  
Vol 37 (6) ◽  
pp. 749-759 ◽  
Author(s):  
R. T. Frizzell ◽  
G. K. Hendrick ◽  
D. W. Biggers ◽  
D. B. Lacy ◽  
D. P. Donahue ◽  
...  

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

Diabetes ◽  
1993 ◽  
Vol 42 (11) ◽  
pp. 1626-1634 ◽  
Author(s):  
A. Avogaro ◽  
P. Beltramello ◽  
L. Gnudi ◽  
A. Maran ◽  
A. Valerio ◽  
...  

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