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Departments of Pathology and Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130
Troglitazone is a peroxisome proliferator-activated receptor-
agonist that has been shown to halt mesangium expansion in experimental
models of type 2 diabetes mellitus and to act directly on rat mesangial
cells. Because glutamine serves as the precursor for cellular
biosynthetic processes, we asked whether troglitazone would inhibit
mesangial cell glutamine metabolism under these conditions. Confluent
monolayers of rat mesangial cells were incubated in RPMI medium in the
presence of troglitazone or vehicle (DMSO). Troglitazone effected a
dose-dependent reduction in glutamine utilization and in alanine
formation, associated with a decrease in monolayer
collagen-glycosaminoglycan content. Despite the reduced glutamine
uptake, ammonium formation did not decrease, consistent with increased
glutamate flux through the deamination pathway. Assayable activity of
the alanine aminotransferase decreased by 63%, whereas assayable
glutamate dehydrogenase remained unchanged. In control monolayers, the
sum of ammonium plus alanine plus glutamate nitrogen released accounted
for <75% of the glutamine nitrogen uptake. In troglitazone-treated
monolayers, all of the glutamine nitrogen taken up could be accounted
for as ammonium nitrogen released into the medium. These results are
consonant with troglitazone reducing glutamine metabolism and
specifically the transamination pathway in rat mesangial cells
associated with a reduction in collagen-glycosaminoglycan content.
peroxisome proliferator-activated receptor-; alanine
aminotransferase; matrix proteins; intracellular pH
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