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.
Rodríguez-Gil
J E
JE
Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Autonomous University of Barcelona, Spain.
Gómez-Foix
A M
AM
Fillat
C
C
Bosch
F
F
Guinovart
J J
JJ
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