Vanadate regulates glucose transporter (Glut-1) expression in NIH3T3 mouse fibroblasts.
Vanadate, the major oxidized form of the essential trace element vanadium, has rapid effects on glucose transport in vitro and more delayed effects on glucose transport in vivo. We addressed the question that one potential mechanism for the delayed effects of vanadate on glucose homeostasis could be altered expression of one or more of the genes encoding glucose transporters. To do this we studied vanadate regulation of Glut-1 and Glut-4 in NIH3T3 mouse fibroblasts. Vanadate (5-40 microM) induced cells to proliferate to higher cell densities, and in addition, 40 microM vanadate caused the cells to exhibit a transformed morphology. Glut-1 mRNA was maximally induced 4- to 5-fold over the control value after 6-h exposure to 30 microM vanadate. Unlike the response to serum and growth factors, the vanadate-induced increase in Glut-1 mRNA remained elevated over the control value in the presence of vanadate for 5 days. The vanadate effect was serum dependent and was fully reversible when vanadate was removed from the medium. In the absence of vanadate, the half-life of Glut-1 mRNA was 0.5-1 h, whereas after treatment for 5 h with 30 microM vanadate the half-life was increased to 1.5-2 h. Thus, mRNA stabilization accounts for at least a part of the increase in glucose transporter mRNA levels after vanadate treatment. Glut-4 mRNA was not detected in these cells in either the absence or presence of vanadate. While the importance of this increased Glut-1 gene expression for the vanadate effect on normalization of blood glucose in vivo remains to be determined, an association between vanadate-induced cell proliferation and transformed phenotype, and vanadate-induced Glut-1 mRNA in vitro has been made. Possible potential therapeutic use of vanadate for treatment of diabetes must, therefore, be viewed with caution.
Mountjoy
K G
KG
Charles A. Dana Research Institute, Harvard-Thorndike Laboratory, Beth Israel Hospital, Boston, Massachusetts 02215.
Flier
J S
JS
D000818:Animals; D001769:Blood; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003847:Deoxyglucose / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006031:Glycosylation; D006207:Half-Life; D007700:Kinetics; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000096:biosynthesis; D014638:Vanadates / Q000494:pharmacology*
D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D014638:Vanadates; D003847:Deoxyglucose