Effect of sulfonylureas on hepatic fatty acid oxidation

Journal Article · Fri Aug 01 00:00:00 EDT 1986 · Am. J. Physiol.; (United States)

OSTI ID:6156097

Patel, T B

In isolated rat livers perfused with oleic acid (0.1 mM), infusion of tolbutamide or glyburide decreased the rate of ketogenesis in a dose-dependent manner. The inhibition of fatty acid oxidation was maximal at 2.0 mM and 10 M concentrations of tolbutamide and glyburide, respectively. Neither tolbutamide nor glyburide inhibited ketogenesis in livers perfused with octanoate. The inhibition of hepatic ketogenesis by sulfonylureas was independent of perfusate oleic acid concentration. Additionally, in rat livers perfused with oleic acid in the presence of L-(-)-carnitine (10 mM), submaximal concentrations of tolbutamide and glyburide did not inhibit hepatic ketogenesis. Finally, glyburide infusion into livers perfused with (U- $C)oleic acid (0.1 mM) increased the rate of UC label incorporation into hepatic triglycerides by 2.5-fold. These data suggest that both tolbutamide and glyburide inhibit long-chain fatty acid oxidation by inhibition the key regulatory enzyme, carnitine palmitoyltransferase I, most probably by competing with L-(-)-carnitine.

• Research Organization: Univ. of Tennessee, Memphis
• OSTI ID: 6156097
• Journal Information: Am. J. Physiol.; (United States), Vol. 251:2
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CARBOXYLIC ACIDS
OXIDATION
LIVER
ENZYME ACTIVITY
SULFONAMIDES
BIOCHEMISTRY
CARBON 14 COMPOUNDS
DOSE-RESPONSE RELATIONSHIPS
INHIBITION
OLEIC ACID
RATS
TRANSFERASES
UREA
AMIDES
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIMICROBIAL AGENTS
BODY
CARBONIC ACID DERIVATIVES
CHEMICAL REACTIONS
CHEMISTRY
DIGESTIVE SYSTEM
DRUGS
ENZYMES
GLANDS
LABELLED COMPOUNDS
MAMMALS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
RODENTS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques