Krebs M, Roden M
Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Diabetes Obes Metab. 2005 Nov;7(6):621-32. doi: 10.1111/j.1463-1326.2004.00439.x.
Increased body fat content correlates with insulin resistance and is a key feature of type 2 diabetes. Excessive intake of fat results in deposition of lipids not only in fat tissue but also in skeletal muscle and liver. Subsequently, both plasma and intracellular concentrations of free fatty acids and their metabolites rise and activate signal transduction pathways, which will induce inflammation and impair insulin signalling. Furthermore, elevated circulating lipids impair endothelial function and fibrinolysis, which contributes to the development of vascular disease. Thus, therapeutic strategies aiming at reduction of (intracellular) lipid availability in skeletal muscle and liver and pharmacological modulation of the signalling pathways activated by increased lipid stores represent promising targets for future treatment of insulin resistance and prevention of its complications. This review focuses on the effects of increased lipid availability on the regulation of glucose metabolism in skeletal muscle and liver as well as on vascular function.
体脂含量增加与胰岛素抵抗相关，是2型糖尿病的一个关键特征。脂肪摄入过多不仅会导致脂质在脂肪组织中沉积，还会在骨骼肌和肝脏中沉积。随后，血浆和细胞内游离脂肪酸及其代谢产物的浓度都会升高，并激活信号转导通路，进而引发炎症并损害胰岛素信号传导。此外，循环脂质升高会损害内皮功能和纤维蛋白溶解，这有助于血管疾病的发展。因此，旨在减少骨骼肌和肝脏中（细胞内）脂质可用性以及对脂质储存增加所激活的信号通路进行药理学调节的治疗策略，是未来治疗胰岛素抵抗及其并发症的有前景的靶点。本综述重点关注脂质可用性增加对骨骼肌和肝脏中葡萄糖代谢调节以及血管功能的影响。
