Artemisia SP and Insulin Action/William T. Cefalu

蒿 SP 和胰岛素作用/William T. Cefalu

• 批准号: 8006899
• 负责人: William T. Cefalu
• 金额: $ 52.76万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8006899
• 关键词: Address; Area; Artemisia; Artemisia dracunculus; Arts; Atherosclerosis; Attenuated; Biochemical; Botanicals; Cardiovascular system; Characteristics; Clinical Data; Clinical Research; Data; Development; Funding; Future; Human; Insulin; Insulin Receptor; Insulin Resistance; Intervention; Investigation; Lipids; Liver; Measures; Metabolic syndrome; Nutritional; Pathway interactions; Protein Tyrosine Phosphatase; Proteins; Proteomics; Receptor Signaling; Research Design; Safety; Secondary to; Skeletal Muscle; Supplementation; Techniques; Testing; Tissues; improved; in vivo; insulin sensitivity; lipid metabolism; member; metabolomics; novel; novel strategies; pre-clinical; randomized trial; research clinical testing

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.

胰岛素抵抗是“代谢综合征”的一个关键病理学特征，并且与以下疾病密切相关： 共存的心血管风险因素和加速动脉粥样硬化。营养补充搭配使用 有效提高胰岛素敏感性的植物药物代表了未来一种非常有吸引力和新颖的方法 旨在干预代谢综合征发展的研究。不幸的是，相当大 关于植物补充剂对代谢综合征的影响存在争议，因为植物补充剂很少 关于植物药改善胰岛素体内或细胞作用测量的效果的人体数据 胰岛素作用的各个方面。然而，我们已经证明，一种经过充分表征的蒿提取物 dracunculus L. 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，并且 已经鉴定出新的蛋白质和提取物调节的几种细胞内途径。具体来说，我们的 研究表明，A. dracunulus L. 在细胞内调节胰岛素作用的机制 水平可能是调节胰岛素受体信号传导负调节因子（即蛋白质酪氨酸）的次要因素 磷酸酶，并减少靶组织中的脂质中间体。对于下一个资助周期，调查将 并在两个领域进行拓展。首先，我们将包括其他选定的蒿属成员，代表 近亲和远亲物种，因为目前尚不清楚它们的多样化生化和 分类学特征是相关的。其次，使用“最先进的”代谢组学分析和 蛋白质组学技术，我们将显着扩大研究范围，提供深入而全面的研究 分析蒿提取物在体内的细胞作用机制。改善胰岛素 敏感性。因此，主要目标是评估选定的蒿属植物的综合效果。提取到 增强和改变细胞脂质代谢，同时调节胰岛素负调节因子 骨骼肌和肝脏中的受体信号转导，即 PTP 酶，作为该机制的补充成分 这些植物可增强胰岛素敏感性并减缓代谢综合征的进展。