Effect of glipizide on hepatic fructose 2,6-bisphosphate concentration and glucose metabolism.
Glipizide raised, in a dose-dependent manner, the concentration of fructose 2,6-bisphosphate in hepatocytes isolated from 24-hour fasted rats and incubated in the presence of 10 mmol/L glucose. Simultaneously, the rate of L-lactate production, as well as the rate of 3H2O formation from (3-3H)glucose, increased markedly. The concentration of glipizide calculated as corresponding to the half-maximal effect in these metabolic parameters was 12 to 15 mumol/L. In hepatocytes isolated from fed rats, either normal or made diabetic by treatment with alloxan, glipizide inhibited the conversion of both (U-14C)pyruvate and (U-14C)lactate to (14C)glucose; an inverse correlation was established between hepatocyte fructose 2,6-bisphosphate levels and the rate of gluconeogenesis. The increase of fructose 2,6-bisphosphate concentration elicited by glipizide, which occurs without a significant modification of either 6-phospho-fructo 2-kinase activity or hepatocyte cyclic AMP levels, seems to be related to a significant accumulation of hexose 6-phosphates (glucose 6-phosphate and fructose 6-phosphate) in the hepatic cells.
D000818:Animals; D002747:Chlorpropamide / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005635:Fructosediphosphates / Q000378:metabolism*; D005913:Glipizide / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006598:Hexosediphosphates / Q000378:metabolism*; D006600:Hexosephosphates / Q000378:metabolism; D066298:In Vitro Techniques; D007773:Lactates / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology
D005635:Fructosediphosphates; D006598:Hexosediphosphates; D006600:Hexosephosphates; D007773:Lactates; D013453:Sulfonylurea Compounds; C027652:fructose 2,6-diphosphate; D014044:Tolbutamide; D000242:Cyclic AMP; D005947:Glucose; D002747:Chlorpropamide; D005913:Glipizide