The influence of tolbutamide on fatty acid metabolism in the liver and muscle.

Metabolism of palmitate-14C was studied in the rat liver and muscle incubated with 1 mmol.l-1 tolbutamide in vitro experiments: Tolbutamide reduces the utilization of free fatty acids in the liver by inhibiting their uptake, incorporation into total lipids, and oxidation to 14CO2. Tolbutamide stimulates the incorporation into the triacylglycerol fraction in individual liver lipid fractions and inhibits the incorporation into the free fatty acid fraction. As in the liver, tolbutamide inhibits the uptake, incorporation into total lipids, and oxidation to 14CO2 in the muscle. In individual lipid fractions, tolbutamide only inhibits the incorporation of palmitate into cholesterol esters. It can be concluded that tolbutamide directly interferes with fatty acid metabolism and thus improves glucose utilization and insulin resistance.