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 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.
Monge
L
L
Servicio de Endocrinología Experimental, Clínica Puerta de Hierro, Universidad Autónoma de Madrid, Spain.
Cabello
M A
MA
Samper
B
B
Mojena
M
M
Felíu
J E
JE
D000818:Animals; D002478:Cells, Cultured; D004357:Drug Synergism; D005635:Fructosediphosphates / Q000378:metabolism*; D005943:Gluconeogenesis / Q000187:drug effects*; D006598:Hexosediphosphates / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010732:Phosphofructokinase-1 / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014044:Tolbutamide / Q000494:pharmacology*
D005635:Fructosediphosphates; D006598:Hexosediphosphates; D007328:Insulin; C027652:fructose 2,6-diphosphate; D014044:Tolbutamide; D010732:Phosphofructokinase-1