Prevention of Diabetes with Nutritional Supplements

描述(申请人提供)：2型糖尿病(T2 DM)是一种严重且代价高昂的疾病，在过去20年中发病率急剧上升。目前治疗糖尿病的方法都很昂贵，而且无法预防糖尿病的长期并发症。预防或推迟2型糖尿病发病的新策略将预防或推迟糖尿病并发症的发生，从而减少患者的痛苦，并为医疗保健系统节省数十亿美元。我们最近开发了一种新的2型糖尿病大鼠模型，既表现出成人起病的肥胖诱导的胰岛素抵抗，又表现出胰岛β细胞功能的损害。该模型与人类2型糖尿病更相关，因此是测试糖尿病预防新方法的合适动物模型。我们建议确定几种广泛使用的营养补充剂的有效性，这些营养补充剂已知可以激活PPAR和/或靶向脂质失调、炎症和氧化应激，以预防或延缓T2 DM的发病。我们将追求以下具体目标：具体目标1：我们假设补充omega 3脂肪酸二十碳五烯酸(EPA)将激活PPARα、γ和Delta，并预防或延缓T2 DM的发生。我们还将确定纯化的EPA是否会比鱼油补充剂更有效地缓解糖尿病的发展。具体目标2：我们假设补充α-硫辛酸可以减少氧化应激，从而预防或延缓T2 DM的发生。我们还将调查a-硫辛酸与海洋石油PPAR激活剂(EPA和DMA)联合使用在预防糖尿病方面是否比单独使用a-硫辛酸更有效。在该模型中，建议进一步研究补充剂或补充剂组合有效预防/延缓糖尿病发病的作用机制(S)。

DESCRIPTION (provided by applicant): The prevalence of Type 2 Diabetes Mellitus (T2DM), a serious and costly disease, has increased dramatically in the past 2 decades. Current therapies for diabetes are expensive and are unable to prevent the long-term complications of the disease. New strategies to prevent or delay the onset of type 2 diabetes would prevent or delay the onset of diabetic complications, and therefore decrease patient suffering and save the health care system billions of dollars. We have recently developed a new rat model of type 2 diabetes that exhibits both adult-onset obesity induced insulin resistance and an impairment of pancreatic Beta-cell function. This model is more relevant to type-2 diabetes in humans and therefore an appropriate animal model for testing new approaches for diabetes prevention. We propose to determine the efficacy of several widely used nutritional supplements known to activate PPARs and/or target lipid dysregulation, inflammation, and oxidative stress to prevent or delay the onset of T2DM in this rat model. We will pursue the following specific aims: Specific Aim 1: We hypothesize that supplementation with omega 3 fatty acid eicosapentaenoic acid (EPA) will activate PPARalpha, gamma and delta and prevent or delay the onset of T2DM. We will also determine whether purified EPA will attenuate the development of diabetes more effectively than fish oil supplements. Specific Aim 2: We hypothesize that supplementation with a-lipoic acid will reduce oxidative stress, thereby preventing or delaying onset of T2DM. We will also investigate whether a-lipoic acid in combination with the marine oil PPAR activators (EPA & DMA) will be more effective than a-lipoic acid alone in preventing diabetes. Further studies to investigate the mechanism(s) of action of the supplements or the supplement combinations that are effective in preventing/delaying diabetes onset of diabetes in this model are proposed.