J. Biol. Chem., Vol. 262, Issue 20, 9529-9534, Jul, 1987
Gluconeogenesis from fructose predominates in periportal regions of the liver lobule
I Anundi, FC Kauffman and RG Thurman
Gluconeogenesis from fructose was studied in periportal and pericentral
regions of the liver lobule in perfused livers from fasted,
phenobarbital-treated rats. When fructose was infused in increasing
concentrations from 0.25 to 4 mM, corresponding stepwise increases in
glucose formation by the perfused liver were observed as expected. Rates of
glucose and lactate production from 4 mM fructose were around 100 and 75
mumol/g/h, respectively. Rates of fructose uptake were around 190 mumol/g/h
when 4 mM fructose was infused. 3- Mercaptopicolinate, an inhibitor of
phosphoenolpyruvate carboxykinase, decreased glucose formation from
fructose maximally by 20% suggesting that a fraction of the lactate formed
from fructose is used for glucose synthesis. A good correlation (r = 0.92)
between extra oxygen consumed and glucose produced from fructose was
observed. At low fructose concentrations (less than 0.5 mM), the extra
oxygen uptake was much greater than could be accounted for by glucose
synthesis possibly reflecting fructose 1-phosphate accumulation.
Furthermore, fructose diminished ATP/ADP ratios from about 4.0 to 2.0 in
periportal and pericentral regions of the liver lobule indicating that the
initial phosphorylation of fructose via fructokinase occurs in both regions
of the liver lobule. Basal rates of oxygen uptake measured with miniature
oxygen electrodes were 2- to 3-fold higher in periportal than in
pericentral regions of the liver lobule during perfusions in the
anterograde direction. Infusion of fructose increased oxygen uptake by 65
mumol/g/h in periportal areas but had no effect in pericentral regions of
the liver lobule indicating higher local rates of gluconeogenesis in
hepatocytes located around the portal vein. When perfusion was in the
retrograde direction, however, glucose was synthesized nearly exclusively
from fructose in upstream, pericentral regions. Thus, gluconeogenesis from
fructose is confined to oxygen-rich upstream regions of the liver lobule in
the perfused liver.
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