EFFECTS OF VANADIUM ON INSULIN TARGET TISSUES

钒对胰岛素靶组织的影响

• 批准号: 3243555
• 负责人: FREDERICK G HAMEL
• 金额: $ 9.92万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-02-01 至 1994-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3243555
• 关键词: activation analysis; adipose tissue; glucose metabolism; insulin receptor; laboratory rat; liver cells; metal metabolism; metal metabolism disorder; muscle metabolism; nutrition related tag; phosphatase inhibitor; phosphoprotein phosphatase; protein degradation; receptor binding; toxicant interaction; vanadium

DESCRIPTION: (Principal Investigator's Abstract): Vanadium is increasingly a source of possible toxic effects through the use of fossil fuels and its incorporation into metal alloys. Vanadium in the form of vanadate has been shown to have a number of insulin-mimetic properties when given acutely in vitro. However, the effects of chronic administration on insulin sensitive tissues in vivo is much less well studied. Therefore, the overall purpose of this proposal is to examine the effects of vanadium on insulin-sensitive activities at its target cell sites. The specific objectives are: 1) to determine if vanadate or vanadyl is preferentially accumulated and retained in tissues with insulin-sensitive glucose transport systems; 2) to determine if vanadium alters insulin receptor numbers, binding, or function; 3) to determine if vanadium has effects on insulin-stimulated activities in target tissues; and 4) to determine if vanadium affects insulin metabolism. Rats will be given vanadium, as sodium orthvanadate or vanadyl sulfate, in a liquid diet and a number of insulin-sensitive activities of target tissues measured and compared to control animals. Specifically, various organs will be harvested and the vanadium content determined by neutron activation analysis. Hepatocytes and adipocytes will be isolated from animals and insulin binding analyzed by Scatchard plots. Receptor function will be assessed by assaying its tyrosine kinase activity. Isolated hepatocytes will be assayed for the insulin-sensitive activities of: amino acid transport, inhibition of protein degradation, and glucose incorporation in glycogen. Isolated adipocytes will be assayed for the insulin-sensitive activities of: glucose uptake, glucose incorporation into lipids, glucose oxidation, and anti-lipolysis. Finally, insulin degradation will be studied in perfused liver and isolated hepatocytes to determine if vanadium alters its metabolism. Those studies will allow determination of the effect of vanadium on insulin target tissue and begin analysis of its mechanisms of action.

描述：（主要研究者的摘要）：钒是 越来越多地通过使用化石来造成毒性作用 燃料及其掺入金属合金中。 钒的形式 脱钒酸盐已被证明具有许多胰岛素模拟特性 在体外急性。 但是，慢性给药对 体内胰岛素敏感的组织的研究得多。 所以， 该提案的总体目的是检查钒的影响 在其目标细胞部位的胰岛素敏感活性上。 具体 目标是：1）确定钒酸盐或钒基是否优先 积聚并保留在胰岛素敏感葡萄糖的组织中 运输系统； 2）确定钒是否改变了胰岛素受体 数字，绑定或功能； 3）确定钒是否对 胰岛素刺激的靶组织活性； 4）确定是否 钒影响胰岛素代谢。 大鼠将被给予钒 在液体饮食中，北万酸钠或钒硫酸钠和许多 靶组织的胰岛素敏感活性测量并与 控制动物。 具体而言，将收获各种器官 钒含量通过中子激活分析确定。 肝细胞 将从动物和分析的胰岛素结合中分离脂肪细胞 通过Scatchard图。 受体功能将通过测定其评估 酪氨酸激酶活性。 孤立的肝细胞将被分析 胰岛素敏感活性：氨基酸转运，抑制 蛋白质降解和糖原中的葡萄糖掺入。 孤立 脂肪细胞将用于胰岛素敏感的活动： 葡萄糖摄取，葡萄糖掺入脂质，葡萄糖氧化和 抗脂解。 最后，将研究胰岛素降解 肝脏和孤立的肝细胞，以确定钒是否改变了 代谢。 这些研究将允许确定 钒在胰岛素靶组织上，并开始分析其机制 行动。