Abstract
Sulfonylureas potentiate the cellular action of insulin, not by changing membrane receptor number as previously thought, but by unknown postbinding mechanisms. We investigated the direct effects of tolazamide on fatty acid oxidation in isolated intact liver mitochondria, prepared from fed and fasted rats. Total ketone body formation and CO2 production (x10% of total oxidative products) were measured using 1−14C palmitate. Ketogenesis results are expressed in nmols/min/mg prot. (± SEM).
Changes in CO2 production paralleled those of ketone formation (data not shown). Only mitochondria from fed rats were sensitive to tolazamide inhibition of fatty acid oxidation; this was dose dependent with a maximum attenuation at 4μg/ml. Carnitine acyltransferase activity was unaffected by high dose tolazamide.
In the absence of insulin, sulfonylureas, at levels below therapeutic (20-40μg/ml), attenuate fatty acid oxidation in hepatic mitochondria from fed rats. This inhibition occurs proximal to acetyl CoA formation; perhaps these compounds are related to or intensify a putative insulin mediator released after receptor occupation.
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McCormick, K., Sicoli, R. & Williams, M. INHIBITION OF FATTY ACID OXIDATION BY SULFONYLUREAS. Pediatr Res 18 (Suppl 4), 296 (1984). https://doi.org/10.1203/00006450-198404001-01221
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DOI: https://doi.org/10.1203/00006450-198404001-01221