Immobilization rapidly induces muscle insulin resistance together with the activation of MAPKs (JNK and p38) and impairment of AS160 phosphorylation.
Immobilization rapidly induces muscle insulin resistance together with the activation of MAPKs (JNK and p38) and impairment of AS160 phosphorylation.
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DOI：
10.14814/phy2.12876
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发表时间：
2016-08
影响因子：
2.5
通讯作者：
Kawanaka K
中科院分区：
文献类型：
--
作者：
Kawamoto E;Koshinaka K;Yoshimura T;Masuda H;Kawanaka K
急性短期缺乏运动可诱导骨骼肌对葡萄糖摄取的胰岛素抵抗。我们研究了不活动通过过度激活促炎/应激通路（包括IKK/ i - κB/NF - κB、JNK和p38 MAPK）迅速诱导肌肉胰岛素抵抗的可能性。我们还研究了另一种可能性，即缺乏运动诱导的胰岛素抵抗的快速发展与AS160磷酸化降低有关，AS160是与葡萄糖摄取调节有关的最远的胰岛素信号蛋白。雄性Wistar大鼠单侧后肢固定6小时。固定结束时，解剖固定和对侧非固定后肢的比目鱼肌。固定化在6小时内降低了大鼠比目鱼肌胰岛素刺激的2 -脱氧葡萄糖摄取。这种胰岛素抵抗的快速发展伴随着JNK和p38磷酸化的升高（分别是JNK和p38途径活性的常用指标）。此外，调节神经酰胺生物合成的限速酶SPT2的丰度在固定肌肉中增加。固定不改变i - κBα的丰度（IKK/ i - κB/NF - κB途径活性的常用指标）。AS160在Thr642和Ser588位点的基础磷酸化随着胰岛素抵抗的发展而降低。这些结果表明，不活动诱导的固定肌肉中胰岛素抵抗的快速发展可能与JNK和/或p38的激活增强有关。神经酰胺生物合成途径的升高可能有助于这种激活。我们的研究结果还表明，AS160基础磷酸化的降低可能与缺乏运动诱导的胰岛素抵抗有关。
Acute short‐duration physical inactivity induces the development of insulin resistance for glucose uptake in skeletal muscle. We examined the possibility that inactivity rapidly induces muscle insulin resistance via the excessive activation of proinflammatory/stress pathways including those of IKK/IκB/NF‐κB, JNK, and p38 MAPK. We also examined the other possibility that inactivity‐induced rapid development of insulin resistance is associated with reduced phosphorylation of AS160, the most distal insulin‐signaling protein that have been linked to the regulation of glucose uptake. Male Wistar rats were subjected to unilateral hindlimb immobilization for 6 h. At the end of the immobilization, the soleus muscles from both immobilized and contralateral non‐immobilized hindlimbs were dissected out. Immobilization decreased insulin‐stimulated 2‐deoxyglucose uptake in rat soleus muscle within 6 h. This rapid development of insulin resistance was accompanied by elevated phosphorylation of both JNK and p38 (commonly used indicator of JNK and p38 pathway activity, respectively). In addition, the abundance of SPT2, a rate‐limiting enzyme regulating ceramide biosynthesis, was increased in immobilized muscle. Immobilization did not alter the abundance of IκBα (commonly used indicator of IKK/IκB/NF‐κB pathway activity). The basal phosphorylation of AS160 at Thr642 and Ser588 was decreased together with the development of insulin resistance. These results suggest the possibility that inactivity‐induced rapid development of insulin resistance in immobilized muscle is related to enhanced activation of JNK and/or p38. Elevated ceramide biosynthesis pathway may contribute to this activation. Our results also indicate that decreased basal phosphorylation of AS160 may be involved in inactivity‐induced insulin resistance.