Effects of tolbutamide on gluconeogenesis and glycolysis in isolated perfused rat liver.
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.
Patel
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D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects*; D007657:Ketone Bodies / Q000096:biosynthesis; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014044:Tolbutamide / Q000494:pharmacology*
D007657:Ketone Bodies; D007773:Lactates; D011773:Pyruvates; D002245:Carbon Dioxide; D019344:Lactic Acid; D019289:Pyruvic Acid; D014044:Tolbutamide