Chromium, Cellular Energy Status, Whole Body Energy Bala

描述(申请人提供)：胰岛素抵抗是“代谢综合征”的一个重要病理生理学特征，与共存的心血管危险因素和加速的动脉粥样硬化密切相关。通过药物手段改善胰岛素抵抗的策略代表了临床医学的传统方法。然而，由于普通公众广泛使用膳食补充剂，通过使用有效提高胰岛素敏感性的基于生物的疗法进行营养补充，为未来旨在干预代谢综合征发展的研究提供了一种非常有吸引力的新方法。铬已被提议作为一种这样的治疗方法。不幸的是，关于铬对人体新陈代谢的影响仍存在相当大的争议，因为在人类中，关于所提出的作用机制的数据很少，因此，铬仍然是仅有的作用机制未知的痕量矿物之一。我们最近的发现表明，在长期的观察期内补充铬可以显著减轻受试者的体重增加和体脂百分比。观察到的体重和脂肪储存的变化将表明铬通过增加能量消耗和/或改变饮食摄入量来改善全身能量平衡的新机制。此外，我们提供的实验证据表明，导致细胞能量状态的一个主要事件，即AMP激酶的激活，似乎是铬的细胞靶标。AMP激酶的激活可以增加葡萄糖的摄取，减少肝脏葡萄糖的产生，增加脂肪酸的氧化，增强细胞信号转导。因此，作为正在进行的铬补充试验的一部分，该项目的总体目标是对铬对2型糖尿病受试者全身能量平衡、脂肪代谢和细胞能量状态的影响进行探索性研究。我们假设，在2型糖尿病患者中，铬将增强细胞AMP激酶的激活，导致骨骼肌脂代谢和脂肪组织功能的增加。这些发现将与改善全身能量平衡有关，并将为计划更大规模、更具确定性的临床研究提供初步数据。

DESCRIPTION (provided by applicant): Insulin resistance is a key pathophysiologic feature of the "metabolic syndrome" and is strongly associated with co-existing cardiovascular risk factors and accelerated atherosclerosis. Strategies to improve insulin resistance by pharmacological means have represented the traditional approach for clinical medicine. However, because of the widespread use of dietary supplements by the general public, nutritional supplementation with the use of biologically based therapies that effectively increase insulin sensitivity represent a very attractive and novel approach for future studies designed to intervene in the development of metabolic syndrome. Chromium has been proposed as one such therapy. Unfortunately, considerable controversy exists regarding the effect of chromium in human metabolism as there is a paucity of data in humans in regard to proposed mechanism of action, and as such, chromium remains as one of the only trace minerals where the mechanism of action is not known. Our recent findings have suggested that chromium supplementation over a long-term period of observation may significantly attenuate weight gain and percent body fat in human subjects. The observed change in body weight and fat stores would suggest a novel new mechanism for chromium to improve whole body energy balance by enhancing energy expenditure and/or altering dietary intake. In addition, we provide experimental evidence to suggest that a primary event contributing to cellular energy status, i.e. activation of AMP kinase, appears to be a cellular target for chromium. Activation of AMP kinase is known to enhance glucose uptake, reduce hepatic glucose production, increase oxidation of fatty acids and enhance cellular signaling. Thus, this project's overall objective is to perform exploratory studies on the effect of chromium on whole body energy balance, lipid metabolism, and cellular energy status in subjects with Type 2 diabetes as part of an ongoing chromium supplementation trial. We hypothesize that, in subjects with type 2 diabetes, chromium will enhance cellular AMP kinase activation resulting in an increase in skeletal muscle lipid metabolism and adipose tissue function These findings will be associated with an improved whole body energy balance and will provide the preliminary data in order to plan larger more definitive clinical research studies.