p300 or CBP is required for insulin-stimulated glucose uptake in skeletal muscle and adipocytes.
p300 or CBP is required for insulin-stimulated glucose uptake in skeletal muscle and adipocytes.
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DOI：
10.1172/jci.insight.141344
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发表时间：
2022-01-11
期刊：
影响因子：
8
通讯作者：
Schenk S
中科院分区：
文献类型：
--
作者：
Martins VF;LaBarge SA;Stanley A;Svensson K;Hung CW;Keinan O;Ciaraldi TP;Banoian D;Park JE;Ha C;Hetrick B;Meyer GA;Philp A;David LL;Henry RR;Aslan JE;Saltiel AR;McCurdy CE;Schenk S
虽然目前的观点认为，骨骼肌和脂肪细胞中葡萄糖转运蛋白 4 (GLUT4) 胞吐易位和葡萄糖摄取的胰岛素信号传导是由基于磷酸化的信号传导控制的，但该途径中的许多蛋白质在赖氨酸残基上被乙酰化。然而，乙酰化和赖氨酸乙酰转移酶对胰岛素刺激的葡萄糖摄取的重要性尚未完全确定。在这里，我们证明小鼠骨骼肌中乙酰转移酶 E1A 结合蛋白 p300 (p300) 和 cAMP 反应元件结合蛋白结合蛋白 (CBP) 的联合丢失导致胰岛素刺激的葡萄糖摄取完全丧失。同样，对 p300/CBP 乙酰转移酶活性的短暂（即 1 小时）药理学抑制在人类和啮齿动物肌管、3T3-L1 脂肪细胞和小鼠肌肉中重现了这种表型。从机制上讲，这些效应是由于 p300/CBP 介导的 GLUT4 胞吐易位调节所致，并发生在 Akt 信号传导下游。总之，我们强调乙酰化和 p300/CBP 在直接调节骨骼肌和脂肪细胞中胰岛素刺激的葡萄糖转运中的基本作用。
While current thinking posits that insulin signaling to glucose transporter 4 (GLUT4) exocytic translocation and glucose uptake in skeletal muscle and adipocytes is controlled by phosphorylation-based signaling, many proteins in this pathway are acetylated on lysine residues. However, the importance of acetylation and lysine acetyltransferases to insulin-stimulated glucose uptake is incompletely defined. Here, we demonstrate that combined loss of the acetyltransferases E1A binding protein p300 (p300) and cAMP response element binding protein binding protein (CBP) in mouse skeletal muscle caused a complete loss of insulin-stimulated glucose uptake. Similarly, brief (i.e., 1 hour) pharmacological inhibition of p300/CBP acetyltransferase activity recapitulated this phenotype in human and rodent myotubes, 3T3-L1 adipocytes, and mouse muscle. Mechanistically, these effects were due to p300/CBP-mediated regulation of GLUT4 exocytic translocation and occurred downstream of Akt signaling. Taken together, we highlight a fundamental role for acetylation and p300/CBP in the direct regulation of insulin-stimulated glucose transport in skeletal muscle and adipocytes.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
微管在胰岛素刺激的葡萄糖转运蛋白 4 易位中的预对接作用
影响因子：
5.4
作者：
Chen, Yu;Wang, Yan;Xu, Tao
通讯作者：
Xu, Tao
影响因子：
5.3
作者：
Huang, WC;Chen, CC
通讯作者：
Chen, CC
影响因子：
3.3
作者：
Fujita H;Hatakeyama H;Watanabe TM;Sato M;Higuchi H;Kanzaki M
通讯作者：
Kanzaki M