Sulfonylurea stimulates liver fructose-2,6-bisphosphate formation in proportion to its hypoglycemic action.
The effects of 5 sulfonylureas on fructose-2,6-bisphosphate (F-2,6-P2) formation using isolated perfused rat liver were examined. All sulfonylureas examined stimulated dose-dependent formation of the activator in a limited range of the concentration. A maximum effect on F-2,6-P2 formation was observed at the concentration of 10(-3) M of tolbutamide or chlorpropamide, at 10(-4) M of gliclazide or acetohexamide and at 10(-6) M of glibenclamide. These concentrations of sulfonylurea correspond with those in blood when therapeutical doses of the drug are administered orally. Sulfonamide and biguanide did not show any stimulatory effect on F-2,6-P2 level. The results demonstrate that stimulation of liver F-2,6-P2 formation is a common characteristic of sulfonylureas and suggest strongly that one of the extrapancreatic actions of sulfonylurea is stimulation of F-2,6-P2 formation followed by enhancement of glycolysis and inhibition of gluconeogenesis in the liver.
D000092:Acetohexamide / Q000494:pharmacology; D000818:Animals; D002026:Buformin / Q000494:pharmacology; D002747:Chlorpropamide / Q000494:pharmacology; D005635:Fructosediphosphates / Q000096:biosynthesis*; D005907:Gliclazide / Q000494:pharmacology; D005943:Gluconeogenesis / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects; D006598:Hexosediphosphates / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013420:Sulfamethoxazole / Q000494:pharmacology; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology
D005635:Fructosediphosphates; D006598:Hexosediphosphates; D013453:Sulfonylurea Compounds; C027652:fructose 2,6-diphosphate; D014044:Tolbutamide; D005907:Gliclazide; D013420:Sulfamethoxazole; D000092:Acetohexamide; D005905:Glyburide; D002026:Buformin; D002747:Chlorpropamide