AJP - Gastrointestinal and Liver Physiology, Vol 263, Issue 3 293-G300, Copyright © 1992 by American Physiological Society
Hypoxic liver injury and the ameliorating effects of fructose: the "glucose paradox" revisited
C. A. Brass, J. M. Crawford, J. Narciso and J. L. Gollan
Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts.
It has been independently postulated that nutritional status is a modulator
of the hepatic injury response to hypoxia and that glucose may be a poor
substrate for hepatocellular metabolism. This study provides data linking
these two concepts within the framework of metabolic zonation of the liver.
With the use of a hypoxically perfused isolated rat liver model, cellular
injury, as reflected by aspartate aminotransferase (AST) release, was
significantly greater in the liver of fasted (mean AST 489 U/g liver at 3
h) than fed (40 U/g) animals. The extent of injury during hypoxia was
decreased to a comparable degree in fasted livers perfused with Wisconsin
solution (27 U/g) or 20 mM fructose (51 U/g). Perfusion with (11.5 mM)
glucose plus insulin provided no hepatoprotection (791 U/g); however,
supraphysiological amounts of glucose (100 mM) with (310 U/g) or without
(321 U/g) insulin (10 U) or dihydroxyacetone (220 U/g) provided a modest
reduction in AST release. Cellular injury measured by trypan blue uptake
showed a marked zonal pattern, with upstream regions incurring greater
parenchymal and nonparenchymal injury than downstream areas. These data
that indicate that exogenous glucose is poorly utilized as an energy
substrate by the liver during hypoxia are consistent with data from the
fasted-refed rat model, suggesting a "glucose paradox" in the liver. The
findings also suggest that low levels of oxygen are an important factor
mediating "hypoxic" liver injury.
