Effects of vanadium-containing compounds on membrane lipids and on microdomains used in receptor-mediated signaling.
There is increasing evidence for the involvement of plasma membrane microdomains in insulin receptor function. Moreover, disruption of these structures, which are typically enriched in sphingomyelin and cholesterol, results in insulin resistance. Treatment strategies for insulin resistance include the use of vanadium (V) compounds which have been shown in animal models to enhance insulin responsiveness. One possible mechanism for insulin-enhancing effects might involve direct effects of V compounds on membrane lipid organization. These changes in lipid organization promote the partitioning of insulin receptors and other receptors into membrane microdomains where receptors are optimally functional. To explore this possibility, we have used several strategies involving V complexes such as [VO(2)(dipic)](-) (pyridin-2,6-dicarboxylatodioxovanadium(V)), decavanadate (V(10)O(28)(6-), V(10)), BMOV (bis(maltolato)oxovanadium(IV)), and [VO(saltris)](2) (2-salicylideniminato-2-(hydroxymethyl)-1,3-dihydroxypropane-oxovanadium(V)). Our strategies include an evaluation of interactions between V-containing compounds and model lipid systems, an evaluation of the effects of V compounds on lipid fluidity in erythrocyte membranes, and studies of the effects of V-containing compounds on signaling events initiated by receptors known to use membrane microdomains as signaling platforms.
Roess
Deborah A
DA
Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1872, USA.
Smith
Steven M L
SML
Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1872, USA.
Winter
Peter
P
Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1872, USA.
Zhou
Jun
J
Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1872, USA.
Dou
Ping
P
Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1872, USA.
Baruah
Bharat
B
Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, USA.
Trujillo
Alejandro M
AM
Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, USA.
Levinger
Nancy E
NE
Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, USA.
Yang
Xioda
X
Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100083, P. R. China.
Barisas
B George
BG
Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, USA.
Crans
Debbie C
DC
Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, USA.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods / Q000592:standards; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D021962:Membrane Microdomains / Q000187:drug effects* / Q000378:metabolism*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000494:pharmacology*; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*; D012015:Reference Standards; D015398:Signal Transduction / Q000187:drug effects*; D014639:Vanadium / Q000494:pharmacology*
D051275:Glucose Transporter Type 4; D007328:Insulin; D008024:Ligands; D008563:Membrane Lipids; D009942:Organometallic Compounds; C495694:Slc2a4 protein, rat; D014639:Vanadium; D011972:Receptor, Insulin; D002118:Calcium