Artemisia SP and Insulin Action/William T. Cefalu

胰岛素抵抗是“代谢综合征”的一个关键的病理特征，与 心血管危险因素并存与动脉粥样硬化加速。营养补充剂配合使用 有效提高胰岛素敏感性的植物药物代表了一种非常有吸引力的未来新方法 旨在干预代谢综合征发展的研究。不幸的是，相当多 关于植物补充剂对代谢综合征的影响存在争议，因为缺乏 关于植物药物对改善体内或细胞内胰岛素作用的测量的影响的数据 胰岛素作用的各个方面。然而，我们已经证明了一种具有良好特征的艾草提取物 龙血竭在细胞水平调节胰岛素受体信号，增加体内胰岛素敏感性，并 已经确定了新的蛋白质和几个受该提取物调控的细胞内途径。具体地说，我们的 研究表明，龙舌兰调节胰岛素在细胞内作用的机制。 水平可能次于调节胰岛素受体信号的负调控因子，即蛋白质-酪氨酸 磷酸酶，以及降低靶组织中的脂质中间体。在下一个供资周期，调查将 在两个方面进行扩展。首先，我们将包括其他精选的蒿属成员，代表 既有亲缘关系又有远亲的物种，因为尚不清楚它们的多样性生化和 相关的分类特征也是相关的。其次，通过使用“最先进的”代谢组谱和 蛋白质组学技术，我们将大幅扩大研究范围，提供深入而全面的 蒿属植物提取物体内作用的细胞机制分析。改善胰岛素 敏感度。因此，主要目标是评估选定的蒿属植物的综合效果。提取到 增强和改善细胞脂代谢，同时调节胰岛素负调控因子 骨骼肌和肝脏中的受体信号转导，即PTPase，作为该机制的补充成分，通过 这些植物药可增强胰岛素敏感性，延缓代谢综合征的进展。

Insulin resistance is a key pattioptiysiologic feature ofthe "metabolic syndrome" and is strongly associated with co-existing cardiovascular rislc factors and accelerated atherosclerosis. Nutritional supplementation with the use of botanicals that effectively increase insulin sensitivity represent a very attractive and novel approach for future studies designed to intervene in the development of metabolic syndrome. Unfortunately, considerable controversy exists regarding the effect of botanical supplements on the metabolic syndrome as there is a paucity of data in humans in regard to the effect of botanicals to improve measures of insulin action in vivo or on cellular aspects of insulin action. However, we have demonstrated that a well characterized extract of Artemisia dracunculus L. regulates insulin receptor signaling at the cellular level, increases insulin sensitivity in vivo, and have identified novel proteins and several intracellular pathways modulated by the extract. Specifically, our studies have demonstrated that the mechanism by which A. dracunulus L. regulates insulin action at the cellular level may be secondary to modulating negative regulators of insulin receptor signaling, i.e. protein-tyrosine phosphatases, and reducing lipid intermediates in target tissues. For the next funding cycle, investigations will be expanded in two areas. First, we will include other selected members ofthe Artemisia genus representing both closely and distantly related species since it remains unclear how their diverse biochemical and taxonomical characteristics are related. Secondly, with use of "state ofthe art" metabolomic profiling and proteomic techniques, we will significantly expand investigations to provide in-depth and comprehensive analysis ofthe cellular mechanisms of action operative in vivo by which extracts of Artemisia sp. improve insulin sensitivity. Thus, the primary objective is to evaluate the combined effects of selected Artemisia sp. extracts to enhance and modify cellular lipid metabolism while simultaneously modulating negative regulators of insulin receptor signaling, i.e. PTPases, in skeletal muscle and liver as complementary components ofthe mechanism by which these botanicals enhance insulin sensitivity and attenuate the progression to metabolic syndrome.