Han Xiao X, Holst Jens J, Galbo Henrik
Department of Rheumatology, Institute of Inflammation Research, Rigshospitalet, University of Copenhagen, Tagensvej 20, 2200 Copenhagen, Denmark.
Department of Biomedical Sciences, NovoNordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
J Pers Med. 2022 May 20;12(5):837. doi: 10.3390/jpm12050837.
Background: Established neuroendocrine signals do not sufficiently account for the exercise-induced increase in glucose production. Using an innovative, yet classical cross-circulation procedure, we studied whether contracting muscle produces a factor that directly stimulates hepatic glycogenolysis. Methods: Isolated rat hindquarters were perfused in series with isolated livers. Results: Stimulation of the sciatic nerve of one or both legs resulted in an increase in force, which rapidly waned. During one-legged contractions, hepatic glucose production increased initially (from −0.9 ± 0.5 (mean ± SE) to 3.3 ± 0.7 µmol/min, p < 0.05). The peak did not differ significantly from that seen after 20 nM of epinephrine (5.1 ± 1.2 µmol/min, p > 0.05). In response to two-legged contractions, the increase in hepatic glucose production (to 5.4 ± 1.3 µmol/min) was higher (p < 0.05) and lasted longer than that seen during one-legged contractions. During contractions, peak hepatic glucose output exceeded concomitant hepatic lactate uptake (p < 0.05), and glucose output decreased to basal levels, while lactate uptake rose to a plateau. Furthermore, in separate experiments an increase in lactate supply to isolated perfused livers increased lactate uptake, but not glucose output. In intact rats, intra-arterial injection of extract made from mixed leg muscle elicited a prolonged increase (p < 0.05) in plasma glucose concentration (from 5.2 ± 0.1 mM to 8.3 ± 1.5 mM). In perfused livers, muscle extract increased glucose output dose dependently. Fractionation by chromatography of the extract showed that the active substance had a MW below 2000. Conclusion: This study provides evidence that contracting skeletal muscle may produce a hormone with a MW below 2000, which enhances hepatic glycogenolysis according to energy needs. Further chemical characterization is warranted.
已确立的神经内分泌信号不足以解释运动引起的葡萄糖生成增加。我们采用一种创新但经典的交叉循环程序，研究收缩的肌肉是否产生一种直接刺激肝糖原分解的因子。方法：将分离的大鼠后肢与分离的肝脏进行串联灌注。结果：刺激一条或两条腿的坐骨神经会导致力量增加，但这种增加会迅速减弱。在单腿收缩期间，肝脏葡萄糖生成最初增加（从−0.9±0.5（平均值±标准误）微摩尔/分钟增加到3.3±0.7微摩尔/分钟，p<0.05）。该峰值与20纳摩尔肾上腺素作用后的峰值（5.1±1.2微摩尔/分钟，p>0.05）无显著差异。响应双腿收缩时，肝脏葡萄糖生成的增加（至5.4±1.3微摩尔/分钟）更高（p<0.05），且持续时间比单腿收缩时更长。在收缩期间，肝脏葡萄糖输出峰值超过同时期肝脏乳酸摄取量（p<0.05），葡萄糖输出降至基础水平，而乳酸摄取量升至平台期。此外，在单独的实验中，向分离的灌注肝脏增加乳酸供应会增加乳酸摄取，但不会增加葡萄糖输出。在完整大鼠中，动脉内注射混合腿部肌肉制成的提取物会使血浆葡萄糖浓度持续增加（p<0.05）（从5.2±0.1毫摩尔/升增加到8.3±1.5毫摩尔/升）。在灌注肝脏中，肌肉提取物剂量依赖性地增加葡萄糖输出。通过对提取物进行色谱分离表明，活性物质的分子量低于2000。结论：本研究提供了证据表明，收缩的骨骼肌可能产生一种分子量低于2000的激素，该激素根据能量需求增强肝糖原分解。有必要进行进一步的化学表征。
