Ulk1, Not Ulk2, Is Required for Exercise Training-Induced Improvement of Insulin Response in Skeletal Muscle.
Ulk1, Not Ulk2, Is Required for Exercise Training-Induced Improvement of Insulin Response in Skeletal Muscle.
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DOI：
10.3389/fphys.2021.732308
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发表时间：
2021
影响因子：
4
通讯作者：
Yan Z
中科院分区：
文献类型：
--
作者：
Drake JC;Wilson RJ;Cui D;Guan Y;Kundu M;Zhang M;Yan Z
Unc 51像自噬激活激酶1（Ulk 1），主要的自噬调节剂，已被链接到骨骼肌代谢适应运动训练。在这里，我们比较了Ulk 1和同源Ulk 2在运动训练后骨骼肌胰岛素作用中的作用，以获得更多的机制见解。诱导性骨骼肌特异性Ulk 1基因敲除（Ulk 1-iMKO）小鼠和整体Ulk 2基因敲除（Ulk 2-/-）小鼠进行6周的自主轮跑，然后在推注胰岛素后评估运动能力、葡萄糖耐量和骨骼肌中的胰岛素信号传导。Ulk 1-iMKO和Ulk 2-/-小鼠在运动后的耐力运动能力都有所提高。在葡萄糖耐量试验期间，Ulk 1-iMKO没有改善葡萄糖清除率，而Ulk 2-/-仅略有改善。然而，运动训练诱导的骨骼肌中胰岛素作用的改善（由Akt-S473磷酸化指示）仅在Ulk 1-iMKO中受损。这些数据表明，Ulk 1，而不是Ulk 2，是运动训练诱导的骨骼肌胰岛素作用的改善所必需的，这意味着分解代谢和合成代谢信号之间的串扰是能量应激代谢适应的组成部分。
Unc51 like autophagy activating kinase 1 (Ulk1), the primary autophagy regulator, has been linked to metabolic adaptation in skeletal muscle to exercise training. Here we compared the roles of Ulk1 and homologous Ulk2 in skeletal muscle insulin action following exercise training to gain more mechanistic insights. Inducible, skeletal muscle-specific Ulk1 knock-out (Ulk1-iMKO) mice and global Ulk2 knock-out (Ulk2–/–) mice were subjected to voluntary wheel running for 6 weeks followed by assessment of exercise capacity, glucose tolerance, and insulin signaling in skeletal muscle after a bolus injection of insulin. Both Ulk1-iMKO and Ulk2–/– mice had improved endurance exercise capacity post-exercise. Ulk1-iMKO did not improve glucose clearance during glucose tolerance test, while Ulk2–/– had only marginal improvement. However, exercise training-induced improvement of insulin action in skeletal muscle, indicated by Akt-S473 phosphorylation, was only impaired in Ulk1-iMKO. These data suggest that Ulk1, but not Ulk2, is required for exercise training-induced improvement of insulin action in skeletal muscle, implicating crosstalk between catabolic and anabolic signaling as integral to metabolic adaptation to energetic stress.
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AMP激活的蛋白激酶对ULK1（HATG1）的磷酸化将能量传感连接到线粒体。
DOI：
10.1126/science.1196371
发表时间：
2011-01-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Egan DF;Shackelford DB;Mihaylova MM;Gelino S;Kohnz RA;Mair W;Vasquez DS;Joshi A;Gwinn DM;Taylor R;Asara JM;Fitzpatrick J;Dillin A;Viollet B;Kundu M;Hansen M;Shaw RJ
通讯作者：
Shaw RJ
影响因子：
16.6
作者：
Laker RC;Drake JC;Wilson RJ;Lira VA;Lewellen BM;Ryall KA;Fisher CC;Zhang M;Saucerman JJ;Goodyear LJ;Kundu M;Yan Z
通讯作者：
Yan Z
影响因子：
13.3
作者：
McAlpine, Fiona;Williamson, Leon E.;Chan, Edmond Y. W.
通讯作者：
Chan, Edmond Y. W.
影响因子：
13.3
作者：
Lee, Eun-Ju;Tournier, Cathy
通讯作者：
Tournier, Cathy
影响因子：
13.3
作者：
Loeffler, Antje S.;Alers, Sebastian;Stork, Bjoern
通讯作者：
Stork, Bjoern