[New biological actions of vanasium].
The effects of vanadate on lipoprotein lipase (LPL), a lipid-metabolizing enzyme, were tested using isolated rat fat pads. Vanadate increased the cellular LPL content through the stimulation of intracellular transport of the enzyme for activation, probably glycosylation. The stimulated release of LPL from the fat pads by vanadate was due to the increase in intracellular Ca2+ concentration, leading to the fusion of plasma membrane with vehicle included active LPL. Although vanadate shows insulin- and heparin-mimicking effects, it appears to differ from both insulin and heparin with regard to the mechanism of action. In isolated mouse fat pads, vanadate decreased the cellular leptin content and secretion by the increased degradation via a cAMP/PKA-dependent process involving proteasome activation and/or ubiquitination. This was the reverse of the action of insulin. In hepatocytes, cAMP phosphodiesterase type 3 activity was stimulated via the increased mitogen-activated protein kinase activity by vanadate. On the other hand, the stimulation by insulin was dependent on Akt kinase activation. The effects of vanadate were additive to those of insulin, suggesting that vanadate differs from insulin with regard to the receptor-signaling cascade. Furthermore, vanadate showed antiplatelet and antithrombin activity, leading to the prolongation of blood clotting time.
Ueki
Hiroshi
H
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 1 Gakuen-cho, Fukuyama 729-0292, Japan. h-ueki@mvh.biglobe.ne.jp
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D008071:Lipoprotein Lipase / Q000378:metabolism*; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D014638:Vanadates / Q000494:pharmacology*
D020738:Leptin; D009097:Multienzyme Complexes; D014638:Vanadates; D000242:Cyclic AMP; D020929:Mitogen-Activated Protein Kinase Kinases; D008071:Lipoprotein Lipase; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D002118:Calcium