Activation by vanadate of glycolysis in hepatocytes from diabetic rats.
In hepatocytes from starved streptozocin-induced diabetic rats, vanadate increases the glycolytic flux because it raises the levels of fructose-2,6-bisphosphate (Fru-2,6-P2), the main regulatory metabolite of this pathway. This effect of vanadate on Fru-2,6-P2 levels is time and dose dependent, and it remains in cells incubated in a calcium-depleted medium. Vanadate is also able to counteract the decrease on Fru-2,6-P2 levels produced by glucagon, colforsin, or exogenous cAMP. However, vanadate does not modify 6-phosphofructo-2-kinase and pyruvate kinase activities, but it does counteract the inactivation of these enzymes induced by glucagon. Likewise, Fru-2,6-P2ase activity is also not affected by vanadate. In addition, vanadate is able to increase the production of both lactate and CO2 in hepatocytes from streptozocin-induced diabetic rats incubated in the presence of glucose in the medium. Vanadate behaves as a glycolytic effector in these cells, and this effect may be related to its ability to normalize blood glucose levels in diabetic animals.
Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Autonomous University of Barcelona, Spain.
J E
JE
Rodríguez-Gil
A M
AM
Gómez-Foix
C
C
Fillat
F
F
Bosch
J J
JJ
Guinovart
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005635:Fructosediphosphates / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014638:Vanadates / Q000494:pharmacology*
D005635:Fructosediphosphates; D014638:Vanadates; C027652:fructose 2,6-diphosphate