Hepatic intralobular mapping of fructose metabolism in the rat liver

2000 ◽  
Vol 349 (2) ◽  
pp. 539-545 ◽  
Author(s):  
Shamus P. BURNS ◽  
Helena C. MURPHY ◽  
Richard A. ILES ◽  
Rosemary A. BAILEY ◽  
Robert D. COHEN

Detailed mapping of glucose and lactate metabolism along the radius of the hepatic lobule was performed in situ in rat livers perfused with 1.5 mM lactate before and during the addition of 5 mM fructose. The majority of fructose uptake occurred in the periportal region; 45% of fructose taken up in the periportal half of the lobular volume being converted into glucose. Periportal lactate uptake was markedly decreased by addition of fructose. Basal perivenous lactate output, which was derived from glucose synthesized periportally, was increased in the presence of fructose. During fructose infusion there was a small decrease in cell pH periportally, but acidification of up to 0.5 pH units perivenously. The evidence suggests that in situ the apparent direct conversion of fructose into lactate represents, to a substantial extent, the result of periportal conversion of fructose into glucose and the subsequent uptake and glycolysis to lactate in the perivenous zone of some of that glucose. 31P NMR spectroscopy showed that the cellular concentration of phosphomonoesters changes very little periportally during fructose infusion, but there was an approximate twofold increase perivenously, presumably due to the accumulation of fructose 1-phosphate. It may be inferred that fructokinase activity is expressed throughout the hepatic lobule.

1973 ◽  
Vol 45 (4) ◽  
pp. 543-549 ◽  
Author(s):  
M. H. Lloyd ◽  
R. A. Iles ◽  
B. R. Simpson ◽  
J. M. Strunin ◽  
J. M. Layton ◽  
...  

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.


1985 ◽  
Vol 82 (24) ◽  
pp. 8747-8751 ◽  
Author(s):  
P. A. Bottomley ◽  
R. J. Herfkens ◽  
L. S. Smith ◽  
S. Brazzamano ◽  
R. Blinder ◽  
...  

1996 ◽  
Vol 319 (2) ◽  
pp. 377-383 ◽  
Author(s):  
Shamus P BURNS ◽  
Robert D. COHEN ◽  
Richard A ILES ◽  
Jocelyn P. GERMAIN ◽  
Thomas C. H. GOING ◽  
...  

A method is described for the production of detailed maps of intralobular variations of hepatocyte function and metabolite concentrations, based on variable destruction by digitonin of the lobule from the centrilobular direction. Instead of the conventional approach, in which isolated hepatocytes are then prepared and studied in suspension, perfusion is continued after digitonin treatment and the function of the unaffected lobular remnants is determined, or mean metabolite concentrations are measured by 31P-NMR. These measurements are plotted against the degree of destruction, determined precisely after each study by automated quantitative histomorphometry. These plots are transformed into curves of the function or metabolite concentration of nominal single cells at any point along the radius of the lobule. Gluconeogenesis from lactate remained stable, although reduced, even after 85–90% lobular destruction, predominated periportally and disappeared by 50% along the radius of the lobule. In 31P-NMR studies, employing 1.5 mM lactate as substrate, narrowing of the intracellular Pi resonance was observed as digitonin destruction increased; this was attributed to a decrease in the intralobular heterogeneity of the intracellular pH, which fell from approx. 7.9 to < 7.4 along the first 16% of the lobular radius (from the periportal end) and to < 7.3 in the remainder of the lobule. The ATP concentration rose, and then fell, along the radius of the lobule in a centripetal direction. The method is potentially generally applicable to a wide range of hepatocellular functions and to the measurement of metabolite concentrations, most conveniently those susceptible to estimation by NMR.


2000 ◽  
Vol 278 (4) ◽  
pp. G542-G550 ◽  
Author(s):  
Niazy Selim ◽  
Gene D. Branum ◽  
Xia Liu ◽  
Richard Whalen ◽  
Thomas D. Boyer

Phenobarbital and other xenobiotics induce drug-metabolizing enzymes, including glutathione S-transferase A1/A2 (rGSTA1/A2). We examined the mechanism of induction of rGSTA1/A2 in rat livers after phenobarbital treatment. The induction of rGSTA1/A2 was not uniform across the hepatic lobule; steady-state transcript levels were threefold higher in perivenous hepatocytes relative to periportal hepatocytes when examined by in situ hybridization 12 h after a single dose of phenobarbital. Administration of a second dose of phenobarbital 12 or 24 h after the first dose did not equalize the induction of rGSTA1/A2 across the lobule. The transcriptional activity of the rGSTA1/A2 gene was increased 3.5- to 5.5-fold in whole liver by phenobarbital, but activities were the same in enriched periportal and perivenous subpopulations of hepatocytes from phenobarbital-treated animals. The half-life of rGSTA1/A2 mRNA in control animals was 3.6 h, whereas it was 10.2 h in phenobarbital-treated animals. We conclude that phenobarbital induces rGSTA1/A2 expression by increasing transcriptional activity across the lobule but induction of rGSTA1/A2 is greater in perivenous hepatocytes due to localized stabilization of mRNA transcripts.


1983 ◽  
Vol 80 (24) ◽  
pp. 7491-7495 ◽  
Author(s):  
A. P. Koretsky ◽  
S. Wang ◽  
J. Murphy-Boesch ◽  
M. P. Klein ◽  
T. L. James ◽  
...  

2020 ◽  
Author(s):  
Ashraf Ismail ◽  
Sanaz Molaye Moghaddam ◽  
Jean-Pierre MetabanzoulouSarya Aziz ◽  
Jacqueline Sedman ◽  
Mazen Bahadi

Author(s):  
Eliška Procházková ◽  
Hubert Hřebabecký ◽  
Radim Nencka ◽  
Martin Dračínský

1993 ◽  
Vol 34 (4) ◽  
pp. 397-404
Author(s):  
B. Moesgaard ◽  
I. Errebo Larsen ◽  
B. Quistorff ◽  
I. Therkelsen ◽  
V. Grøsfjeld Christensen ◽  
...  

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