AJP - Endocrinology and Metabolism, Vol 250, Issue 1 82-E86, Copyright © 1986 by American Physiological Society
Effects of tolbutamide on gluconeogenesis and glycolysis in isolated perfused rat liver
T. B. Patel
In isolated perfused livers of 24-h fasted rats, perfused with lactate (2
mM), pyruvate (0.5 mM), or dihydroxyacetone (1 mM), infusion of tolbutamide
(0.5 mM) very rapidly (within 3 min) inhibited the rate of gluconeogenesis.
However, gluconeogenesis from fructose (1 mM) and glycerol (1 mM) was not
affected by tolbutamide. Tolbutamide also inhibited by 30% the rate of
14CO2 production from livers perfused with [1-14C]pyruvate, without
altering the rate of 14CO2 production from [2-14C]pyruvate. The rate of
hepatic glycolysis from fructose, glycerol, and dihydroxyacetone was also
stimulated by 250, 40, and 100%, respectively, during tolbutamide infusion
into perfused livers. Tolbutamide also inhibited the endogenous rate of
hepatic ketogenesis by 30%. All of the tolbutamide-mediated alterations in
hepatic metabolism were reversed upon withdrawal of tolbutamide from the
perfusion medium. Decreased hepatic gluconeogenesis from lactate and
pyruvate in the presence of tolbutamide was not a consequence of increased
pyruvate oxidation via the pyruvate dehydrogenase complex or the
tricarboxylic acid cycle.
