Multifunctional actions of vanadium compounds on insulin signaling pathways: Evidence for preferential enhancement of metabolic versus mitogenic effects
Multifunctional actions of vanadium compounds on insulin signaling pathways: Evidence for preferential enhancement of metabolic versus mitogenic effects
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DOI：
10.1023/a:1006853426679
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发表时间：
1998-05-01
影响因子：
4.3
通讯作者：
Tsiani, E
中科院分区：
文献类型：
--
作者：
Fantus, IG;Tsiani, E
胰岛素抵抗在肥胖和糖尿病等疾病中具有重要的病理生理意义，人们对胰岛素的作用机制以及克服导致胰岛素抵抗的生化缺陷的方法产生了极大的兴趣。钒化合物已被发现在体外和体内模拟胰岛素的许多代谢作用，并改善糖尿病患者的血糖控制。除了其直接的胰岛素模拟作用外，我们还发现钒酸盐通过增强胰岛素敏感性和延长胰岛素作用来调节胰岛素代谢效应。所有这些作用似乎都与蛋白酪氨酸磷酸酶(PTP)抑制有关。然而，与其刺激作用相反，钒酸抑制基础和胰岛素刺激的A系统氨基酸摄取和细胞增殖。这些作用的机制似乎也与PTP抑制有关，这与PTPs在调节信号转导中的多种作用一致。虽然钒酸盐作用的确切生化途径尚不清楚，但它与胰岛素明显不同，因为胰岛素受体和磷脂酰肌醇3‘-激酶似乎不是钒酸刺激葡萄糖摄取和代谢所必需的，钒化合物在以胰岛素抵抗为特征的疾病中绕过胰岛素作用缺陷的能力，以及它们明显的优先代谢和有丝分裂信号特征使它们成为潜在的药理药物。
The pathophysiologic importance of insulin resistance in diseases such as obesity and diabetes mellitus has led to great interest in defining the mechanism of insulin action as well as the means to overcome the biochemical defects responsible for the resistance. Vanadium compounds have been discovered to mimic many of the metabolic actions of insulin both in vitro and in vivo and improve glycemic control in human subjects with diabetes mellitus. Apart from its direct insulinmimetic actions, we found that vanadate modulates insulin metabolic effects by enhancing insulin sensitivity and prolonging insulin action. All of these actions appear to be related to protein tyrosine phosphatase (PTP) inhibition. However, in contrast to its stimulatory effects, vanadate inhibits basal and insulin-stimulated system A amino acid uptake and cell proliferation. The mechanism of these actions also appears to be related to PTP inhibition, consistent with the multiple roles of PTPs in regulating signal transduction. While the precise biochemical pathway of vanadate action is not yet known, it is clearly different from that of insulin in that the insulin receptor and phosphatidylinositol 3'-kinase do not seem to be essential for vanadate stimulation of glucose uptake and metabolism, The ability of vanadium compounds to 'bypass' defects in insulin action in diseases characterized by insulin resistance and their apparent preferential metabolic versus mitogenic signaling profile make them attractive as potential pharmacological agents.