Department of Medical Biochemistry, University of Belgrade, Serbia.
Biol Trace Elem Res. 2010 Jun;134(3):296-306. doi: 10.1007/s12011-009-8474-y. Epub 2009 Jul 31.
Investigations of effective, orally active, and safe antidiabetic metallopharmaceuticals have been carried out during the last two decades. It has been reported that tungsten compounds mimic the action of insulin in intact cell systems. As insulin mimetics, the most investigated tungsten compound was sodium tungstate (ST), rarely investigated was tungstophosphoric acid (WPA), but never alanine complex of tungstophosphoric acid (WPA-A). In this study, the insulin mimetic activity of three different tungsten compounds, ST, WPA, and WPA-A, was evaluated by means of in vitro measurements of the glucose uptake and inhibition of free fatty acids release from epinephrine-treated isolated rat white adipocytes. We investigated the influence of concentration (lower and higher, 0.1 and 1.0 mM, respectively) and solvent: isotonic salt solution-saline (0.9% w/v of NaCl) and dimethyl sulfoxide (DMSO; 2% v/v), on the biological effect of tested compounds. Our experimental data showed that all of the three investigated tungsten compounds possess insulin mimetic activity in vitro on the isolated adipocytes. Influence of concentration and solvents on insulin mimetic effect for the certain tungsten compounds were: WPA was shown effect independently of concentration and solvents; higher concentration and DMSO were significant decreasing insulin mimetic effect of ST; lower concentration and saline led to decreasing effect of WPA-A. Generally, there were no differences in insulin mimetic effect of three tungsten compounds in lower concentration and dissolved in DMSO. When saline was used as solvent, it was needed higher concentration of investigated compounds to accomplish the same effect. In conclusion, our results suggest that low concentration (0.1 mM) of ST, WPA, and WPA-A dissolved in 2% DMSO could be the good candidates for in vivo investigation of their antidiabetic properties.
在过去的二十年中,人们一直在研究有效、口服活性和安全的抗糖尿病金属药物。据报道,钨化合物在完整的细胞系统中模拟胰岛素的作用。作为胰岛素模拟物,研究最多的钨化合物是钨酸钠(ST),很少研究的是钨磷酸(WPA),但从未研究过钨磷酸-丙氨酸复合物(WPA-A)。在这项研究中,通过测量葡萄糖摄取和抑制肾上腺素处理的分离大鼠白色脂肪细胞中游离脂肪酸释放,评估了三种不同的钨化合物 ST、WPA 和 WPA-A 的胰岛素模拟活性。我们研究了浓度(低浓度和高浓度,分别为 0.1 和 1.0 mM)和溶剂(等渗盐溶液-生理盐水(0.9%w/v 的 NaCl)和二甲基亚砜(DMSO;2%v/v))对测试化合物生物效应的影响。我们的实验数据表明,三种研究的钨化合物在体外分离的脂肪细胞中均具有胰岛素模拟活性。浓度和溶剂对某些钨化合物胰岛素模拟作用的影响为:WPA 独立于浓度和溶剂表现出作用;高浓度和 DMSO 显著降低 ST 的胰岛素模拟作用;低浓度和生理盐水导致 WPA-A 的胰岛素模拟作用降低。一般来说,在低浓度(0.1 mM)和溶解在 DMSO 中时,三种钨化合物的胰岛素模拟作用没有差异。当生理盐水用作溶剂时,需要更高浓度的研究化合物才能达到相同的效果。总之,我们的结果表明,低浓度(0.1 mM)的 ST、WPA 和 WPA-A 溶解在 2%DMSO 中可能是体内研究它们抗糖尿病特性的良好候选物。