Effects of Vanadium‐Containing Compounds on Membrane Lipids and on Microdomains Used in Receptor‐Mediated Signaling

Abstract

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 compounds which have been shown in animal models to enhance insulin responsiveness. One possible mechanism for insulin-enhancing effects might involve direct effects of vanadium 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 vanadium complexes such as [VO2dipic]− (pyridin-2,6-dicarboxylatodioxovanadium(V)), decavanadate (V10O286−, V10), 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 vanadium-containing compounds and model lipid systems, an evaluation of the effects of vanadium compounds on lipid fluidity in erythrocyte membranes, and studies of the effects of vanadium-containing compounds on signaling events initiated by receptors known to use membrane microdomains as signaling platforms.

Counterion Affects Interaction with Interfaces: The Antidiabetic Drugs Metformin and Decavanadate

“…Recently, studies of how vanadium compounds interact with interface model systems and traverse membranes [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] have shown that several anionic complexes readily penetrate the interfaces, [16,17,20,21,26] but large oxometalates such as V 10 reside away from a negatively charged interface and close to a positively charged interface, as expected. [19][20][21]23,24,27,28] Because counterions can affect the properties, a suitable counterion choice could poten-By using 51 V NMR spectroscopy, we found only small differences between the metformium and Na + decavanadate materials. However, by using IR spectroscopy, the decavanadate-metformin material was found to affect the water pool and water organization near the interface of the reverse micelles differently.…”

“…Previous studies with NaV 10 solutions at different pH values showed V 10 in the center of the water droplets. [19][20][21]23,24,28] Taken in combination, these studies suggest that the environment for the V 10 in HMetV 10 is similar to that of NaV 10 . V 10 species in acidic solution added to AOT/isooctane exchanged the excess amount of protons with sodium cations.…”

“…The interaction of V 10 with interfaces has been investigated in cells as well as in simple model systems such as reverse micelles (RMs) prepared from an organic solvent, water, and a surfactant. [19,21,23,24,28,36] Whereas RMs can be prepared from a range of different surfactants, bis(2-ethylhexyl)sulfosuccinate (AOT; Figure 1, d) is the surfactant most frequently used. The RMs form a dynamic system, generally assumed to be spherical with a radius proportional to the w 0 = [H 2 O]/[AOT] ratio.…”

Vanadium in Therapy and Toxicity; Mini-Review and Recommendation of Further Study

“…The mechanism by which vanadium restricts elevation of plasma cholesterol appears to involve both inhibition of cholesterol synthesis as well as accelerated catabolism of cholesterol. 3 Vanadium is considered an important element for normal cell function and its development. 4,5 Katheren H 6 and co-workers have investigated several metal compounds such as vanadium, zinc, cobalt, chromium and molybdenum to be therapeutic agents in treating diabetes mellitus.…”

Gel Formulation Containing Mixed Surfactant and Lipids Associating with Carboplatin

“…1) surfactant blend system forming the basis of an implantable surfactant-based gel system for chemotherapeutic action containing a targeting agent. À in AOT/isooctane microemulsions [55]. An upfield chemical shift in the past has been interpreted to indicate molecule penetration deep into the non-polar surfactant region, whereas no change in chemical shift suggests that molecule is residing in the H 2 O pool [56] [57].…”