Nistala Ravi, Stump Craig S
Department of Internal Medicine, University of Missouri-Columbia, Columbia, MO USA.
J Cardiometab Syndr. 2006 Winter;1(1):47-52. doi: 10.1111/j.0197-3118.2006.05455.x.
The cardiometabolic syndrome is associated with insulin resistance and a dysregulation of glucose and lipid metabolism that occurs in multiple tissues. Of these, skeletal muscle is the most abundant insulin-sensitive tissue, handling > 40% of the postprandial glucose uptake, while consuming 20% of the body's energy. The inability to efficiently take up and store fuel, and to transition from fat to glucose as the primary source of fuel during times of plenty (increased insulin), has been termed metabolic inflexibility. This resistance to insulin is thought to be a major contributor to the whole-body metabolic dysregulation that leads to increased cardiovascular risk. Recent investigation has identified specific defects in postinsulin receptor signaling in skeletal muscle from resistant humans and animals. Potential mechanisms contributing to this reduced insulin signaling and action include decreases in mitochondrial oxidative capacity, increased intramuscular lipid accumulation, increased reactive oxygen species generation, and up-regulated inflammatory pathways. Future research is focused on understanding these and other potential mechanisms to identify therapeutic targets for reducing cardiometabolic syndrome risk.
心血管代谢综合征与胰岛素抵抗以及多组织中发生的葡萄糖和脂质代谢失调有关。其中，骨骼肌是最丰富的胰岛素敏感组织，处理超过40%的餐后葡萄糖摄取，同时消耗身体20%的能量。在营养充足（胰岛素增加）时无法有效地摄取和储存燃料，以及无法从脂肪转变为葡萄糖作为主要燃料来源，被称为代谢灵活性受损。这种对胰岛素的抵抗被认为是导致全身代谢失调进而增加心血管疾病风险的主要因素。最近的研究已经确定了胰岛素抵抗的人类和动物骨骼肌中胰岛素受体后信号传导的特定缺陷。导致胰岛素信号传导和作用降低的潜在机制包括线粒体氧化能力下降、肌肉内脂质积累增加、活性氧生成增加以及炎症途径上调。未来的研究重点是了解这些及其他潜在机制，以确定降低心血管代谢综合征风险的治疗靶点。
