Fasting potentiates insulin-mediated glucose uptake in rested and prior-contracted rat skeletal muscle
Fasting potentiates insulin-mediated glucose uptake in rested and prior-contracted rat skeletal muscle
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禁食增强休息和先前收缩的大鼠骨骼肌中胰岛素介导的葡萄糖摄取
DOI：
10.1152/ajpendo.00412.2021
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发表时间：
2022
影响因子：
5.1
通讯作者：
Hayashi Tatsuya
中科院分区：
文献类型：
--
作者：
Kido Kohei;Egawa Tatsuro;Watanabe Shinya;Kawanaka Kentaro;Treebak Jonas T.;Hayashi Tatsuya
单次运动可以通过激活AMPK-TBC 1结构域家族成员4（TBC 1D 4）途径增强胰岛素对骨骼肌葡萄糖摄取的影响，这表明AMPK激活与胰岛素敏化之间存在正相关性。此外，已知啮齿类动物中的长时间禁食上调，从而协同增强运动对肌肉AMPK活化的作用。因此，禁食可能会增强运动的胰岛素增敏作用。在本研究中，我们模仿运动，在原位肌肉收缩和评估的影响，36小时的快速肌肉收缩诱导的胰岛素增敏。将体重150-170 g的雄性Wistar大鼠分配到36 h禁食组或喂养组。通过腓总神经电收缩趾长伸肌（EDL）肌肉10分钟，然后是3小时的恢复期。将EDL肌肉解剖并在存在或不存在次最大胰岛素的情况下孵育。我们的研究结果表明，急性肌肉收缩和36小时的禁食相加上调AMPK通路的激活。胰岛素刺激的肌肉葡萄糖摄取和位点特异性TBC 1D 4磷酸化增强先前肌肉收缩36小时禁食大鼠，但不是在喂养大鼠。此外，胰岛素诱导的肌肉葡萄糖摄取和Akt磷酸化由于36小时的禁食与减少tribbles同源物3（TRB 3），Akt激活的负调节。总之，禁食和先前的肌肉收缩协同增强胰岛素刺激的TBC 1D 4磷酸化和葡萄糖摄取，这与增强AMPK通路激活在啮齿动物。新&值得注意的是在这项研究中，我们发现，36小时的禁食加性上调急性肌肉收缩诱导的AMPK通路激活大鼠。此外，禁食和肌肉收缩协同增强胰岛素刺激的位点特异性TBC 1D 4磷酸化和葡萄糖摄取，这与增强AMPK通路活化有关。这些结果有助于了解肌肉胰岛素敏感性的调节。
A single bout of exercise can potentiate the effect of insulin on skeletal muscle glucose uptake via activation of the AMPK-TBC1 domain family member 4 (TBC1D4) pathway, which suggests a positive correlation between AMPK activation and insulin sensitization. In addition, prolonged fasting in rodents is known to upregulate and thereby synergistically enhance the effect of exercise on muscle AMPK activation. Therefore, fasting may potentiate the insulin-sensitizing effect of exercise. In the present study, we mimicked exercise by in situ muscle contraction and evaluated the effect of a 36-h fast on muscle contraction-induced insulin sensitization. Male Wistar rats weighing 150–170 g were allocated to either a 36-h fasting or feeding group. The extensor digitorum longus (EDL) muscles were electrically contracted via the common peroneal nerve for 10 min followed by a 3-h recovery period. EDL muscles were dissected and incubated in the presence or absence of submaximal insulin. Our results demonstrated that acute muscle contraction and 36 h of fasting additively upregulated AMPK pathway activation. Insulin-stimulated muscle glucose uptake and site-specific TBC1D4 phosphorylation were enhanced by prior muscle contraction in 36-h-fasted rats, but not in fed rats. Moreover, enhanced insulin-induced muscle glucose uptake and Akt phosphorylation due to 36 h of fasting were associated with a decrease in tribbles homolog 3 (TRB3), a negative regulator of Akt activation. In conclusion, fasting and prior muscle contraction synergistically enhance insulin-stimulated TBC1D4 phosphorylation and glucose uptake, which is associated with augmented AMPK pathway activation in rodents.NEW & NOTEWORTHYIn this study, we revealed that 36 h of fasting additively upregulated acute muscle contraction-induced AMPK pathway activation in rats. Besides, fasting and muscle contraction synergistically enhanced insulin-stimulated site-specific TBC1D4 phosphorylation and glucose uptake, which was associated with augmented AMPK pathway activation. These results contribute to understanding the regulation of muscle insulin sensitivity.