Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Rev Endocr Metab Disord. 2013 Jun;14(2):207-16. doi: 10.1007/s11154-013-9242-z.
The skeletal muscle is one of the major target organs of insulin and plays an essential role in insulin-induced glucose uptake. Some evidence indicates that insulin delivery to skeletal muscle interstitium through the endothelial cells is the rate-limiting step in insulin-stimulated glucose uptake. Researchers have also found that this process is impaired by insulin resistance in type 2 diabetes and obesity. A recent study of ours demonstrated that insulin signaling in the endothelial cells plays a pivotal role in the regulation of glucose uptake by the skeletal muscle. Specifically, impaired insulin signaling in the endothelial cells, with reduction of insulin-induced eNOS phosphorylation, causes attenuation of the insulin-induced capillary recruitment and insulin delivery, which, in turn reduces glucose uptake by the skeletal muscle in high-fat diet-fed mice. Moreover, restoration of the insulin-induced eNOS phosphorylation in the endothelial cells completely reverses the reduction in the capillary recruitment and insulin delivery, and as a result, significantly restores glucose uptake by the skeletal muscle. In the present review, we describe the recent progress in research on the physiological and pathophysiological roles of endothelial insulin signaling in the regulation of insulin-induced glucose uptake by the skeletal muscle.
骨骼肌是胰岛素的主要靶器官之一，在胰岛素诱导的葡萄糖摄取中起着至关重要的作用。有证据表明，胰岛素通过内皮细胞向骨骼肌间质的输送是胰岛素刺激葡萄糖摄取的限速步骤。研究人员还发现，在 2 型糖尿病和肥胖症中，这一过程受到胰岛素抵抗的损害。我们最近的一项研究表明，内皮细胞中的胰岛素信号在调节骨骼肌葡萄糖摄取中起着关键作用。具体来说，内皮细胞中胰岛素信号的受损，伴随着胰岛素诱导的 eNOS 磷酸化减少，导致胰岛素诱导的毛细血管募集和胰岛素输送的减弱，进而降低高脂肪饮食喂养的小鼠骨骼肌的葡萄糖摄取。此外，内皮细胞中胰岛素诱导的 eNOS 磷酸化的恢复完全逆转了毛细血管募集和胰岛素输送的减少，结果显著恢复了骨骼肌的葡萄糖摄取。在本综述中，我们描述了内皮细胞胰岛素信号在调节胰岛素诱导的骨骼肌葡萄糖摄取中的生理和病理生理作用的最新研究进展。
