CREG1 stimulates AMPK phosphorylation and glucose uptake in skeletal muscle cells
CREG1 stimulates AMPK phosphorylation and glucose uptake in skeletal muscle cells
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DOI：
10.1016/j.bbrc.2022.12.028
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发表时间：
2022-12-16
影响因子：
3.1
通讯作者：
Yamashita，Hitoshi
中科院分区：
文献类型：
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作者：
Goto，Ayumi;Endo，Yuki;Yamashita，Hitoshi
腺病毒早期区域 1A 刺激基因 1 (CREG1) 的细胞阻遏蛋白是一种参与细胞分化和能量代谢的分泌糖蛋白。它还与胰岛素样生长因子 2 受体 (IGF2R) 结合，这是一种与肌肉再生有关的蛋白质。然而，CREG1是否通过IGF2R调节骨骼肌的再生和代谢仍不清楚。本研究探讨了 CREG1 在 C2C12 肌管和心脏毒素 (CTX) 诱导的小鼠骨骼肌再生模型中骨骼肌再生和葡萄糖摄取中的作用。 CTX 处理的骨骼肌显示 IGF2R、CREG1、磷酸化 AMPKα Thr172 和 GLUT4 蛋白水平显着升高。同样，用 CREG1 处理肌管也刺激 AMPKα 磷酸化和 GLUT4 表达。 CREG1 诱导的 AMPKα 磷酸化和肌管中 2DG 的摄取被 IGF2R 敲低和 AMPK 抑制剂化合物 C 抑制。这些结果表明 CREG1 部分通过 AMPK 激活来刺激骨骼肌中的葡萄糖摄取。因此，CREG1 通过影响骨骼肌中的葡萄糖代谢在肌肉再生中发挥重要作用。
The cellular repressor of adenovirus early region 1A-stimulated gene 1 (CREG1) is a secreted glycoprotein involved in cell differentiation and energy metabolism. It also binds to insulin-like growth factor 2 receptor (IGF2R), a protein implicated in muscle regeneration. However, whether CREG1 regulates the regeneration and metabolism of skeletal muscles via IGF2R remains unclear. This study investigates the role of CREG1 in skeletal muscle regeneration and glucose uptake in C2C12 myotubes and a cardiotoxin (CTX)-induced mouse skeletal muscle regeneration model. CTX-treated skeletal muscle showed significantly higher levels of IGF2R, CREG1, phospho-AMPKα Thr172, and GLUT4 proteins. Similarly, treatment of myotubes with CREG1 also stimulated AMPKα phosphorylation and GLUT4 expression. CREG1-induced AMPKα phosphorylation and 2DG uptake in myotubes were suppressed by IGF2R knockdown and Compound C, an AMPK inhibitor. These results suggest that CREG1 stimulates glucose uptake in skeletal muscles partially through AMPK activation. Hence, CREG1 plays an essential role in muscle regeneration by affecting glucose metabolism in skeletal muscles.