Mechanism of gluconeogenesis inhibition in rat hepatocytes isolated after
in vivo hypoxia.
Pison, Christophe M., Christiane Chauvin, Eric Fontaine, Francoise Catelloni,
Christiane Keriel, Bernard Paramelle, and Xavier M. Leverve.
Laboratoire de Th[acute]erapeutique, Universit[acute]e Joseph Fourier, Bat.
72 Biologie, BP 53X, 38041 Grenoble-Cedex, France. Service de Pneumologie,
Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble-Cedex 9,
France.
APStracts 2:0001E, 1995.
Gluconeogenesis was studied in hepatocytes isolated from fasted rats submitted
to 24h hypoxic exposure (FiO2=0.1) or to room air. Hepatocytes from hypoxic
rats compared to controls exhibited a lower gluconeogenic rate with lactate
(5.1+/-0.3 vs 7.2+/-0.3 [mu]mol/min/g dry cells, p<0.001) but not with
dihydroxyacetone (9.1+/-0.3 vs 9.4+/-0.4 [mu]mol/min/g dry cells), leading to
involve phosphoenolpyruvate/pyruvate cycle. Experiments with perifused
hepatocytes from hypoxic and control rats showed a single relationship
between phosphoenolpyruvate and JGlucose but two different curves when
cytosolic oxaloacetate was plotted against JGlucose. The decreased
phosphoenolpyruvate carboxykinase (PEPCK) activity in hypoxic group (9.0+/-0.9
vs 16.2+/-1.9 nmol/min/mg protein, p<001) without change in Km further settled
the involvement of this step. The significant decrease in PEPCK mRNA levels
in livers from hypoxic rats led us to propose that in vivo hypoxia exposure
inhibits gluconeogenesis at phosphoenolpyruvate carboxykinase by decreasing
PEPCK gene transcription.
Received 23 September 1994; accepted in final form 3 January 1995.
APS Manuscript Number E392-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 February 1995.