Tolbutamide enhances insulin action on gluconeogenesis and on fructose 2,6-bisphosphate levels in isolated rat hepatocytes

In hepatocytes isolated from fed rats and incubated either under basal conditions or in the presence of glucagon, tolbutamide reduced gluconeogenesis from (U-14C) pyruvate by increasing the cellular concentration of fructose 2,6-bisphosphate. Furthermore, this sulfonylurea enhanced the inhibitory ac...

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Bibliographic Details
Published inDiabete & metabolisme Vol. 14; no. 6; p. 712
Main Authors Monge, L, Cabello, M A, Samper, B, Mojena, M, Felíu, J E
Format Journal Article
LanguageEnglish
Published France 01.12.1988
Subjects
Animals
Cells, Cultured
Drug Synergism
Fructosediphosphates - metabolism
Gluconeogenesis - drug effects
Hexosediphosphates - metabolism
Insulin - pharmacology
Kinetics
Liver - drug effects
Liver - metabolism
Male
Phosphofructokinase-1 - metabolism
Rats
Rats, Inbred Strains
Tolbutamide - pharmacology
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Summary:In hepatocytes isolated from fed rats and incubated either under basal conditions or in the presence of glucagon, tolbutamide reduced gluconeogenesis from (U-14C) pyruvate by increasing the cellular concentration of fructose 2,6-bisphosphate. Furthermore, this sulfonylurea enhanced the inhibitory action of insulin on glucagon-stimulated gluconeogenesis; this effect was accompanied by a more marked increase of the cellular concentration of fructose 2,6-bisphosphate than that elicited by either insulin or the sulfonylurea alone. In connection with this, tolbutamide--without significant modification of cellular cyclic AMP levels--raised the proportion of 6-phosphofructo 2-kinase in active form in hepatocytes incubated either under basal conditions or in the presence of glucagon, and reinforced the action of insulin in antagonizing the glucagon-mediated inactivation of this enzyme.
ISSN:0338-1684