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J. Biol. Chem., Vol. 275, Issue 44, 34025-34027, November 3, 2000
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From the Experiments do not support a recent claim that
glutamate formed from the amination of citric acid cycle-derived
ACCELERATED PUBLICATION
Glutamate Is Not a Messenger in Insulin Secretion*
§ and Childrens Diabetes Center and
¶ Department of Pharmacology, University of Wisconsin Medical
School, Madison, Wisconsin 53706
-ketoglutarate is a messenger in glucose-induced insulin secretion
(Maechler, P., and Wollheim, C. (1999) Nature 402, 685-689). Glucose, leucine, succinic acid methyl ester, and
-ketoisocaproic acid all markedly stimulate insulin release but do
not increase glutamate levels in pancreatic islets. Increasing the
intracellular glutamate levels to 10-fold higher than basal levels by
adding glutamine to islets does not stimulate insulin release. When
leucine, in addition to glutamine, is applied to islets, insulin
release is almost as high as with glucose alone. This is consistent
with the known ability of leucine to allosterically activate glutamate
deamination by glutamate dehydrogenase, which can supply
-ketoglutarate to the citric acid cycle. Experiments with
mitochondria from pancreatic islets suggest that flux through the
glutamate dehydrogenase reaction is quiescent during glucose-induced
insulin secretion. These experiments support the traditional idea that
when insulin release is associated with flux through glutamate
dehydrogenase, the flux is in the direction of
-ketoglutarate.
*
This study was supported by National Institutes of Health
Grant DK28348, the Oscar C. Rennebohm Foundation, and the
Robert Wood Johnson Family Trust.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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