The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78245-3207, USA.
Free Radic Biol Med. 2012 Jan 1;52(1):46-58. doi: 10.1016/j.freeradbiomed.2011.10.441. Epub 2011 Oct 20.
The development of metabolic dysfunctions like diabetes and insulin resistance in mammals is regulated by a myriad of factors. Oxidative stress seems to play a central role in this process as recent evidence shows a general increase in oxidative damage and a decrease in oxidative defense associated with several metabolic diseases. These changes in oxidative stress can be directly correlated with increased fat accumulation, obesity, and consumption of high-calorie/high-fat diets. Modulation of oxidant protection through either genetic mutation or treatment with antioxidants can significantly alter oxidative stress resistance and accumulation of oxidative damage in laboratory rodents. Antioxidant mutant mice have previously been utilized to examine the role of oxidative stress in other disease models, but have been relatively unexplored as models to study the regulation of glucose metabolism. In this review, we will discuss the evidence for oxidative stress as a primary mechanism linking obesity and metabolic disorders and whether alteration of antioxidant status in laboratory rodents can significantly alter the development of insulin resistance or diabetes.
哺乳动物中代谢功能障碍（如糖尿病和胰岛素抵抗）的发展受多种因素的调节。氧化应激似乎在这个过程中起着核心作用，因为最近的证据表明，与几种代谢疾病相关的氧化损伤普遍增加，而氧化防御能力下降。氧化应激的这些变化可以与脂肪堆积、肥胖和高卡路里/高脂肪饮食的摄入直接相关。通过基因突变或抗氧化剂治疗来调节氧化剂的保护作用，可以显著改变实验动物的氧化应激抵抗能力和氧化损伤的积累。抗氧化突变小鼠以前曾被用于研究氧化应激在其他疾病模型中的作用，但作为研究葡萄糖代谢调节的模型，它们相对来说还没有被充分探索。在这篇综述中，我们将讨论氧化应激作为将肥胖和代谢紊乱联系起来的主要机制的证据，以及实验动物中抗氧化状态的改变是否可以显著改变胰岛素抵抗或糖尿病的发展。
