Chromium, Cellular Energy Status, Whole Body Energy Bala

铬、细胞能量状态、全身能量巴拉

• 批准号: 6963437
• 负责人: William T. Cefalu
• 金额: $ 22.05万
• 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: 2005-08-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6963437
• 关键词: adenylate kinase; adipocytes; adipose tissue; alternative medicine; bioenergetics; body composition; cell biology; cell differentiation; chromium; clinical research; diabetes mellitus therapy; dietary mineral; dietary supplements; enzyme activity; human subject; human therapy evaluation; insulin sensitivity /resistance; lipid metabolism; metabolic syndrome; muscle metabolism; noninsulin dependent diabetes mellitus; nutrient intake activity; nutrition related tag; patient oriented research

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.

描述（由申请人提供）：胰岛素抵抗是“代谢综合征”的关键病理生理学特征，并且与共存的心血管危险因素和加速动脉粥样硬化密切相关。通过药理学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，由于公众广泛使用膳食补充剂，使用有效提高胰岛素敏感性的生物疗法进行营养补充对于旨在干预代谢综合征发展的未来研究来说是一种非常有吸引力且新颖的方法。铬已被提议作为一种此类疗法。不幸的是，关于铬在人体新陈代谢中的作用存在相当大的争议，因为关于拟议的作用机制的人体数据很少，因此，铬仍然是唯一一种其作用机制尚未确定的微量矿物质之一。已知。我们最近的研究结果表明，经过长期观察，补充铬可能会显着减轻人类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表明铬有一种新颖的机制，可以通过增加能量消耗和/或改变饮食摄入来改善全身能量平衡。此外，我们提供的实验证据表明，影响细胞能量状态的主要事件，即 AMP 激酶的激活，似乎是铬的细胞靶点。已知 AMP 激酶的激活可增强葡萄糖摄取、减少肝葡萄糖生成、增加脂肪酸氧化并增强细胞信号传导。因此，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、脂质代谢和细胞能量状态的影响进行探索性研究，作为正在进行的铬补充试验的一部分。我们假设，在 2 型糖尿病受试者中，铬会增强细胞 AMP 激酶激活，从而增加骨骼肌脂质代谢和脂肪组织功能。这些发现将与改善全身能量平衡相关，并将提供初步数据为了计划更大规模、更明确的临床研究。