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Title: Effect of sulfonylureas on hepatic fatty acid oxidation

Abstract

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.

Authors:
Publication Date:
Research Org.:
Univ. of Tennessee, Memphis
OSTI Identifier:
6156097
Resource Type:
Journal Article
Resource Relation:
Journal Name: Am. J. Physiol.; (United States); Journal Volume: 251:2
Country of Publication:
United States
Language:
English
Subject:
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

Citation Formats

Patel, T.B. Effect of sulfonylureas on hepatic fatty acid oxidation. United States: N. p., 1986. Web.
Patel, T.B. Effect of sulfonylureas on hepatic fatty acid oxidation. United States.
Patel, T.B. Fri . "Effect of sulfonylureas on hepatic fatty acid oxidation". United States.
@article{osti_6156097,
title = {Effect of sulfonylureas on hepatic fatty acid oxidation},
author = {Patel, T.B.},
abstractNote = {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.},
doi = {},
journal = {Am. J. Physiol.; (United States)},
number = ,
volume = 251:2,
place = {United States},
year = {Fri Aug 01 00:00:00 EDT 1986},
month = {Fri Aug 01 00:00:00 EDT 1986}
}