Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
Physiology (Bethesda). 2022 May 1;37(3):115-127. doi: 10.1152/physiol.00034.2021. Epub 2021 Nov 15.
Research conducted over the last 50 yr has provided insight into the mechanisms by which insulin stimulates glucose transport across the skeletal muscle cell membrane Transport alone, however, does not result in net glucose uptake as free glucose equilibrates across the cell membrane and is not metabolized. Glucose uptake requires that glucose is phosphorylated by hexokinases. Phosphorylated glucose cannot leave the cell and is the substrate for metabolism. It is indisputable that glucose phosphorylation is essential for glucose uptake. Major advances have been made in defining the regulation of the insulin-stimulated glucose transporter (GLUT4) in skeletal muscle. By contrast, the insulin-regulated hexokinase (hexokinase II) parallels Robert Frost's "The Road Not Taken." Here the case is made that an understanding of glucose phosphorylation by hexokinase II is necessary to define the regulation of skeletal muscle glucose uptake in health and insulin resistance. Results of studies from different physiological disciplines that have elegantly described how hexokinase II can be regulated are summarized to provide a framework for potential application to skeletal muscle. Mechanisms by which hexokinase II is regulated in skeletal muscle await rigorous examination.
在过去的 50 年中进行的研究提供了对胰岛素刺激葡萄糖跨骨骼肌细胞膜转运机制的深入了解。然而，仅转运本身并不能导致净葡萄糖摄取，因为游离葡萄糖在细胞膜两侧达到平衡，并且不会被代谢。葡萄糖摄取需要己糖激酶将葡萄糖磷酸化。磷酸化的葡萄糖不能离开细胞，是代谢的底物。葡萄糖磷酸化对于葡萄糖摄取是必不可少的，这一点是无可争议的。在定义胰岛素刺激的骨骼肌葡萄糖转运体（GLUT4）的调节方面已经取得了重大进展。相比之下，胰岛素调节的己糖激酶（己糖激酶 II）与罗伯特·弗罗斯特的“未选择的路”相似。这里提出的观点是，理解己糖激酶 II 对葡萄糖的磷酸化作用对于定义健康和胰岛素抵抗状态下骨骼肌葡萄糖摄取的调节是必要的。总结了来自不同生理学学科的研究结果，这些研究优雅地描述了如何调节己糖激酶 II，为其在骨骼肌中的潜在应用提供了框架。己糖激酶 II 在骨骼肌中的调节机制有待严格检查。
