Departments of Kinesiology, Biochemistry & Molecular Biology, and Physiology, Brody School of Medicine, East Carolina Diabetes & Obesity Institute, East Carolina University, Greenville, NC 27858, USA.
Department of Anatomy, Cell Biology & Physiology, and Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Biomolecules. 2022 Nov 23;12(12):1734. doi: 10.3390/biom12121734.
Glucose transporter 1 (GLUT1) is believed to solely mediate basal (insulin-independent) glucose uptake in skeletal muscle; yet recent work has demonstrated that mechanical overload, a model of resistance exercise training, increases muscle GLUT1 levels. The primary objective of this study was to determine if GLUT1 is necessary for basal or overload-stimulated muscle glucose uptake. Muscle-specific GLUT1 knockout (mGLUT1KO) mice were generated and examined for changes in body weight, body composition, metabolism, systemic glucose regulation, muscle glucose transporters, and muscle [H]-2-deoxyglucose uptake ± the GLUT1 inhibitor BAY-876. [H]-hexose uptake ± BAY-876 was also examined in HEK293 cells-expressing GLUT1-6 or GLUT10. mGLUT1KO mice exhibited no impairments in body weight, lean mass, whole body metabolism, glucose tolerance, basal or overload-stimulated muscle glucose uptake. There was no compensation by the insulin-responsive GLUT4. In mGLUT1KO mouse muscles, overload stimulated higher expression of mechanosensitive GLUT6, but not GLUT3 or GLUT10. In control and mGLUT1KO mouse muscles, 0.05 µM BAY-876 impaired overload-stimulated, but not basal glucose uptake. In the GLUT-HEK293 cells, BAY-876 inhibited glucose uptake via GLUT1, GLUT3, GLUT4, GLUT6, and GLUT10. Collectively, these findings demonstrate that GLUT1 does not mediate basal muscle glucose uptake and suggest that a novel glucose transport mechanism mediates overload-stimulated glucose uptake.
葡萄糖转运蛋白 1（GLUT1）被认为仅介导骨骼肌的基础（胰岛素非依赖性）葡萄糖摄取；然而，最近的研究表明，机械超负荷（抗阻运动训练的模型）会增加肌肉 GLUT1 水平。本研究的主要目的是确定 GLUT1 是否是基础或超负荷刺激肌肉葡萄糖摄取所必需的。生成了肌肉特异性 GLUT1 敲除（mGLUT1KO）小鼠，并检查了体重、身体成分、代谢、全身葡萄糖调节、肌肉葡萄糖转运体和肌肉 [H]-2-脱氧葡萄糖摄取的变化，同时使用 GLUT1 抑制剂 BAY-876。还在表达 GLUT1-6 或 GLUT10 的 HEK293 细胞中检查了 [H]-己糖摄取±BAY-876。mGLUT1KO 小鼠的体重、瘦体重、全身代谢、葡萄糖耐量、基础或超负荷刺激肌肉葡萄糖摄取均无受损。胰岛素反应性 GLUT4 没有代偿。在 mGLUT1KO 小鼠肌肉中，超负荷刺激机械敏感 GLUT6 的表达更高，但不是 GLUT3 或 GLUT10。在对照和 mGLUT1KO 小鼠肌肉中，0.05µM 的 BAY-876 会损害超负荷刺激但不损害基础葡萄糖摄取。在 GLUT-HEK293 细胞中，BAY-876 通过 GLUT1、GLUT3、GLUT4、GLUT6 和 GLUT10 抑制葡萄糖摄取。总之，这些发现表明 GLUT1 不介导基础肌肉葡萄糖摄取，并表明一种新的葡萄糖转运机制介导了超负荷刺激的葡萄糖摄取。
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