Hellenic National Center for Research, Prevention and Treatment of Diabetes Mellitus and its Complications, Athens, Greece.
Hormones (Athens). 2013 Apr-Jun;12(2):201-13. doi: 10.14310/horm.2002.1404.
The aim of this review is to summarize the mechanisms underlying insulin resistance in morbid obesity. Glucose regulation by insulin depends on the suppression of endogenous glucose production and stimulation of glucose disposal. In morbid obesity, glucose production by the liver is increased. Moreover, the sensitivity of glucose metabolism to insulin is impaired both in muscle (due to defects in insulin-stimulated glucose utilization and decreased blood flow) and in adipose tissue (due to decreased blood flow). However, recent studies suggest that expanded total fat mass becomes a major consumer of glucose providing a sink for glucose and compensating for insulin resistance. Metabolism and immunity are closely linked. Bearing in mind the crosstalk between inflammatory pathways and the insulin signaling cascade, adipose tissue derived cytokines may represent a link between inflammation and metabolic signals and mediate, at least in part, insulin resistance. Adipose tissue plays a crucial role by buffering daily influx of dietary fat, suppressing the release of non-esterified fatty acids into the circulation and increasing triacylglycerol clearance. However, in morbid obesity there is an impairment of the normal ability of adipose tissue to buffer fatty acids, despite hyperinsulinemia. Lipotoxicity gradually impairs insulin action in the liver and muscle, aggravating insulin resistance.
本篇综述的目的在于总结病态肥胖症中胰岛素抵抗的发生机制。胰岛素控制血糖取决于对内源性葡萄糖生成的抑制和葡萄糖摄取的刺激。在病态肥胖症中，肝脏产生的葡萄糖增加。此外，肌肉（由于胰岛素刺激的葡萄糖利用减少和血流量减少）和脂肪组织（由于血流量减少）中葡萄糖代谢对胰岛素的敏感性受损。然而，最近的研究表明，扩张的总脂肪量成为葡萄糖的主要消耗者，为葡萄糖提供了一个储存库，并补偿了胰岛素抵抗。代谢和免疫密切相关。考虑到炎症途径和胰岛素信号级联之间的串扰，脂肪组织来源的细胞因子可能代表炎症和代谢信号之间的联系，并至少部分介导胰岛素抵抗。脂肪组织通过缓冲每日膳食脂肪的流入、抑制非酯化脂肪酸进入循环的释放以及增加三酰甘油的清除，发挥着至关重要的作用。然而，尽管存在高胰岛素血症，病态肥胖症中脂肪组织缓冲脂肪酸的正常能力受损。脂毒性逐渐损害肝脏和肌肉中的胰岛素作用，加重胰岛素抵抗。
