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(Received for publication, February 27, 1997, and in revised form, April 16, 1997)
From the Diabetes Research Center, Faculty of Medicine, Vrije
Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium, the
¶ Molecular Nutrition Unit, Department of Nutrition, University of
Montreal, Montreal, Quebec H2L 4M1, Canada, and the Previous studies in rat islets have
suggested that anaplerosis plays an important role in the regulation of
pancreatic
Volume 272, Number 30,
Issue of July 25, 1997
pp. 18572-18579
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
GLUCOSE-REGULATED ANAPLEROSIS IN 
CELLS
,
and
Centre de
Recherche L.-C. Simard, Institut du Cancer, Montreal, Quebec H2L 4M1,
Canada
cell function and growth. However, the relative
contribution of islet cells versus non- cells to
glucose-regulated anaplerosis is not known. Furthermore, the fate of
glucose carbon entering the Krebs cycle of islet cells remains to be
determined. The present study has examined the anaplerosis of glucose
carbon in purified rat cells using specific 14C-labeled
glucose tracers. Between 5 and 20 mM glucose, the oxidative production of CO2 from [3,4-14C]glucose
represented close to 100% of the total glucose utilization by the
cells. Anaplerosis, quantified as the difference between 14CO2 production from
[3,4-14C]glucose and [6-14C]glucose, was
strongly influenced by glucose, particularly between 5 and 10 mM. The dose dependence of glucose-induced insulin
secretion correlated with the accumulation of citrate and malate in
(INS-1) cells. All glucose carbon that was not oxidized to
CO2 was recovered from the cells after extraction in
trichloroacetic acid. This indirectly indicates that lactate output is
minimal in cells. From the effect of cycloheximide upon the
incorporation of 14C-glucose into the acid-precipitable
fraction, it could be calculated that 25% of glucose carbon entering
the Krebs cycle via anaplerosis is channeled into protein synthesis. In
contrast, non- cells (approximately 80% glucagon-producing 
cells) exhibited rates of glucose oxidation that were 
to 
those of the total glucose utilization and no detectable
anaplerosis from glucose carbon. This difference between the two cell
types was associated with a 7-fold higher expression of the anaplerotic
enzyme pyruvate carboxylase in cells, as well as a 4-fold lower
ratio of lactate dehydrogenase to FAD-linked glycerol phosphate
dehydrogenase in cells versus cells. Finally,
glucose caused a dose-dependent suppression of the activity
of the pentose phosphate pathway in cells. In conclusion, rat cells metabolize glucose essentially via aerobic glycolysis, whereas
glycolysis in cells is largely anaerobic. The results support the
view that anaplerosis is an essential pathway implicated in cell
activation by glucose.
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