XAFS STUDIES OF METAL ANTI-DIABETIC SUPPLEMENTS AND DRUGS

金属抗糖尿病补充剂和药物的 XAFS 研究

• 批准号: 8170187
• 负责人: PETER A LAY
• 金额: $ 0.27万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170187
• 关键词: Antidiabetic Drugs; Biochemical Pathway; Biodistribution; Biological; Blood Glucose; Cells; Chromium; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Developed Countries; Diabetes Mellitus; Exhibits; Funding; Generations; Grant; Incidence; Institution; Link; Metabolic Diseases; Metals; Muscle; Nature; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Pharmaceutical Preparations; Phosphoric Monoester Hydrolases; Process; Property; Relative Risks; Research; Research Personnel; Resources; Role; Source; Techniques; Testing; United States National Institutes of Health; base; beamline; chromium hexavalent ion; design; diabetic; dietary supplements; oligomycin sensitivity-conferring protein; oxidation; uptake

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Type 2 diabetes is a metabolic disorder characterised by an inability to control blood glucose concentrations. It is strongly linked to obesity, with the greatest incidence of diabetes occurring in the most developed countries. While phosphatase inhibition is the generally accepted mechanism to explain the anti-diabetic effects of V complexes there is much more controversy associated with the role of Cr supplements, and considerable debate still surrounds the exact mode of action, biodistribution and the functions associated with their efficacies. Chromium dietary supplements are the second most popular metal supplements after Ca supplements and are taken for their purported activities as anti-diabetic, slimming and muscle-building capacities. However, the efficacy in anti-diabetic effects is only observed at relatively high concentrations of supplements and we have demonstrated that these generate appreciable amounts of carcinogenic Cr(VI) both intra- and extra-cellularly and in a manner that appears to be dependent on the nature of the supplement. To study Cr speciation in bulk cells with XANES, third generation beamlines are required because of the low uptake of some common supplements. The use of such techniques will enable us to in ascertain whether the biological oxidations observed to date are common to all of the Cr supplements or just certain types. This may be important in assessing their relative risks. We will also investigate the anti-diabetic properties of V complexes that are in clinical trials or are promising candidates for trials. In particular, we will test our hypothesis that V exhibits these properties via the V(V) oxidation states or peroxo species generated by intracellular processes via similar biochemical pathways to those we have investigated in Cr. In doing so, we anticipate that we will be able to design safer and more effective metal-based anti-diabetic drugs.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 2型糖尿病是一种代谢障碍，其特征是无法控制血糖浓度。它与肥胖密切相关，最发达国家发生的糖尿病发生率最高。虽然磷酸酶抑制是解释V复合物的抗糖尿病作用的普遍接受的机制，但与CR补充剂的作用有关，还有更多的争议，并且存在相当大的争论围绕着确切的作用方式，生物分布及其效率相关的功能。铬饮食补充剂是仅次于CA补充剂的第二个最受欢迎的金属补充剂，并以其抗糖尿病，减肥和肌肉建设能力而被视为其据称的活动。然而，仅在相对较高的补充剂浓度下观察到抗糖尿病作用的功效，我们已经证明，这些效应产生了相当大的致癌性CR（VI），并且在外部和外部和外部以及似乎取决于补充性质的方式。为了研究带有XANES的散装细胞中的CR形成，由于某些常见补充剂的吸收率低，因此需要第三代束线。这种技术的使用将使我们能够确定迄今为止观察到的生物氧化是所有CR补充剂还是某些类型的共同点。这对于评估其相对风险可能很重要。我们还将研究临床试验中V复合物的抗糖尿病特性，或者是有望进行试验的候选人。特别是，我们将测试我们的假设，即V通过与我们在CR中研究的类似的生化途径相似的生化途径，通过v（v）氧化态或通过类似的生化途径产生的氧化态或过氧物种表现出这些特性。通过这样做，我们预计我们将能够设计更安全，更有效的基于金属的抗糖尿病药物。