Artemisia SP and Insulin Action/William T. Cefalu

胰岛素抵抗是“代谢综合征”的一个重要病理特征， 同时存在心血管风险因素和加速动脉粥样硬化。营养补充与使用 有效增加胰岛素敏感性的植物药代表了未来非常有吸引力的新方法 旨在干预代谢综合征发展的研究。不幸的是， 关于植物补充剂对代谢综合征的影响存在争议， 关于植物药改善体内或细胞胰岛素作用措施的人体数据 胰岛素的作用。然而，我们已经证明，一个很好的特点提取物蒿 龙血竭在细胞水平调节胰岛素受体信号传导，增加体内胰岛素敏感性， 已经确定了新的蛋白质和几个细胞内的途径调节的提取物。具体来说，我们的 研究表明，A. [医]龙葵属调节胰岛素在细胞内的作用 水平可能继发于调节胰岛素受体信号传导的负调节因子，即蛋白酪氨酸 磷酸酶和减少靶组织中的脂质中间体。在下一个供资周期，调查将 在两个方面扩大。首先，我们将包括蒿属的其他选定成员， 无论是近亲还是远亲物种，因为目前还不清楚它们的多样性生物化学和 分类特征是相关的。其次，使用“最先进的”代谢组学分析， 蛋白质组学技术，我们将大大扩大调查，提供深入和全面的 青蒿提取物改善胰岛素的体内细胞作用机制分析 灵敏度因此，主要目的是评估所选蒿属提取物的组合效果， 增强和改变细胞脂质代谢，同时调节胰岛素负调节因子 受体信号传导，即PTPases，在骨骼肌和肝脏中作为该机制的补充成分， 这些植物药增强胰岛素敏感性并减弱代谢综合征的进展。

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.