Effect of sulfonylureas on hepatic fatty acid oxidation
Journal Article
·
· Am. J. Physiol.; (United States)
OSTI ID:6156097
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), Journal Name: Am. J. Physiol.; (United States) Vol. 251:2; ISSN AJPHA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMIDES
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIMICROBIAL AGENTS
BIOCHEMISTRY
BODY
CARBON 14 COMPOUNDS
CARBONIC ACID DERIVATIVES
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
CHEMISTRY
DIGESTIVE SYSTEM
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENZYME ACTIVITY
ENZYMES
GLANDS
INHIBITION
LABELLED COMPOUNDS
LIVER
MAMMALS
MONOCARBOXYLIC ACIDS
OLEIC ACID
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
OXIDATION
RATS
RODENTS
SULFONAMIDES
TRANSFERASES
UREA
VERTEBRATES
59 BASIC BIOLOGICAL SCIENCES
AMIDES
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIMICROBIAL AGENTS
BIOCHEMISTRY
BODY
CARBON 14 COMPOUNDS
CARBONIC ACID DERIVATIVES
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
CHEMISTRY
DIGESTIVE SYSTEM
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENZYME ACTIVITY
ENZYMES
GLANDS
INHIBITION
LABELLED COMPOUNDS
LIVER
MAMMALS
MONOCARBOXYLIC ACIDS
OLEIC ACID
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
OXIDATION
RATS
RODENTS
SULFONAMIDES
TRANSFERASES
UREA
VERTEBRATES