Boroni Moreira A P, de Cássia Gonçalves Alfenas R
Nutrition Science, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil.
Nutr Hosp. 2012 Mar-Apr;27(2):382-90. doi: 10.1590/S0212-16112012000200007.
The reduction in the capacity of insulin to reach its biological effects can lead to a chronic hyperglycemia and hyperinsulinemia, assuming an important role in the pathogenesis of metabolic disorders associated to obesity and diabetes. Insulin resistance is associated to chronic subclinical inflammation, which in part can be mediated by increased plasmatic lipopolysaccharide levels, an endotoxin derived from the membrane of gramnegative bacteria that mainly reside in the gut.
The aim of this review study is to describe the molecular mechanisms involved in the pathogenesis of insulin resistance due to metabolic endotoxemia and of its connection to obesity and diabetes.
Lipopolysaccharide present in the intestinal lumen can reach the circulatory system causing metabolic endotoxemia. When lipopolysaccharide binds to Toll-like receptor 4, inflammation is activated, changing several stages of insulin signaling. It has been shown that chronic exposure to this endotoxin may contribute to weight gain and type 2 diabetes mellitus manifestation. Obese and diabetic people have increased plasmatic lipopolysaccharide levels. The increase in the number of gram-negative bacteria on gut microbiota, the reduction on gut mucosal integrity, and the consumption of high-fat diets increase the plasmatic lipopolysaccharide levels. Therefore, the type of diet consumed may modulate the composition of gut microbiota and improve gut mucosal integrity, decreasing the occurrence of endotoxemia and its postprandial inflammatory effects, leading to adequate insulin signaling. However, there are very few studies that evaluated the influence of nutrients and/or specific food types on metabolic endotoxemia.
胰岛素发挥生物学效应的能力下降会导致慢性高血糖和高胰岛素血症，在与肥胖和糖尿病相关的代谢紊乱发病机制中起重要作用。胰岛素抵抗与慢性亚临床炎症有关，部分可由血浆脂多糖水平升高介导，脂多糖是一种主要存在于肠道的革兰氏阴性菌细胞膜衍生的内毒素。
本综述研究旨在描述代谢性内毒素血症导致胰岛素抵抗的发病机制及其与肥胖和糖尿病的关联所涉及的分子机制。
肠腔内存在的脂多糖可进入循环系统，导致代谢性内毒素血症。当脂多糖与Toll样受体4结合时，炎症被激活，改变胰岛素信号传导的多个阶段。研究表明，长期接触这种内毒素可能导致体重增加和2型糖尿病的表现。肥胖和糖尿病患者的血浆脂多糖水平升高。肠道微生物群中革兰氏阴性菌数量增加、肠道黏膜完整性降低以及高脂饮食的摄入都会增加血浆脂多糖水平。因此，所摄入的饮食类型可能会调节肠道微生物群的组成，改善肠道黏膜完整性，减少内毒素血症的发生及其餐后炎症效应，从而使胰岛素信号传导正常。然而，很少有研究评估营养素和/或特定食物类型对代谢性内毒素血症的影响。
