A novel mechanism for the insulin-like effect of vanadate on glycogen synthase in rat adipocytes.
Vanadate activated rat adipocyte glycogen synthase similarly to insulin in a dose- and time-dependent manner. No additional effect was observed when insulin and vanadate were added together. Vanadate also partially counteracted the effect of epinephrine to activate rat adipocyte glycogen phosphorylase similarly to insulin. Inhibition of Na+K+ATPase or stimulation of hydrogen peroxide generation were shown not to be the mechanisms of the insulin-like action of vanadate on glycogen synthase. Vanadate stimulated the phosphorylation of the 95,000-dalton subunit of the insulin receptor on tyrosine residues both in intact adipocytes and in a solubilized insulin receptor fraction. Vanadate also stimulated the phosphorylation of the 95,000-dalton subunit of a highly purified insulin receptor from human placenta. Neither the insulin receptor fraction from rat adipocyte nor the highly purified insulin receptor from human placenta contained any detectable phosphotyrosine phosphatase activity. Potassium fluoride had no stimulatory effect on the phosphorylation of the insulin receptor. Vanadate caused a 10-fold decrease in the Km for ATP, for tyrosine kinase, and enhanced the phosphorylation of histone H2B. These results demonstrate that vanadate enhances the phosphorylation of the insulin receptor by stimulating the kinase reaction in a similar but not identical manner to insulin.
D000273:Adipose Tissue / Q000201:enzymology*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism; D014638:Vanadates; D014639:Vanadium / Q000494:pharmacology*
D007328:Insulin; D014639:Vanadium; D014638:Vanadates; D010042:Ouabain; D003847:Deoxyglucose; D002374:Catalase; D006006:Glycogen Synthase; D011972:Receptor, Insulin