AICAR enhances insulin signaling via downregulation of miR-29.
AICAR enhances insulin signaling via downregulation of miR-29.
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DOI：
10.1139/cjpp-2015-0159
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发表时间：
2016-02
影响因子：
2.1
通讯作者：
Jia Liu;Cheng Ye;Wei Liu;Wei Zhao;Ya-jing Zhang;H. Zhang;H. Ying
中科院分区：
文献类型：
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作者：
Jia Liu;Cheng Ye;Wei Liu;Wei Zhao;Ya-jing Zhang;H. Zhang;H. Ying
作为 AMPK 的激活剂，AICAR 对胰岛素信号传导的影响尚未得到广泛研究。 PI3K-Akt 是胰岛素信号通路中的关键节点。我们观察到，伴随着 AICAR 激活 AMPK，小鼠原代肝细胞中 PI3K p85α 的蛋白水平和胰岛素诱导的 Akt 磷酸化得到增强。此前，我们在肝细胞中鉴定了一组 AMPK 调节的 miRNA。目前尚不清楚 miRNA 是否与 AMPK 调节胰岛素信号有关。在这里，我们证实了 AICAR 治疗对小鼠原代肝细胞中 miR-29 家族成员的负调控。我们的结果表明，p85α 是 miR-29 的直接靶标，并在肝细胞中受到 miR-29b 的负向调节。与体外研究结果一致，我们发现禁食小鼠肝脏中 miR-29 的表达和 p85α 的蛋白水平呈负相关。 miR-29b 的过度表达降低了肝细胞中胰岛素诱导的 Akt 磷酸化，表明 miR-29 可以作为胰岛素信号传导的负调节因子。此外，我们发现 miR-29 的过度表达可以减弱 AICAR 对 p85α 表达的影响。综上所述，我们的结果表明 AMPK 的激活可能通过下调 miR-29 来增强胰岛素信号传导。
As an activator of AMPK, the effect of AICAR on insulin signaling has not been investigated extensively. PI3K-Akt is a critical node involved in the insulin signaling pathway. We observed that concomitant with the activation of AMPK by AICAR, the protein level of PI3K p85α and the insulin-induced phosphorylation of Akt were enhanced in mouse primary hepatocytes. Previously, we identified a group of AMPK-regulated miRNAs in hepatocytes. It is not clear whether miRNAs are related to the regulation of insulin signaling by AMPK. Here, we confirmed the negative regulation of miR-29 family members by AICAR treatment in mouse primary hepatocytes. Our results indicated that p85α is a direct target of miR-29 and is negatively regulated by miR-29b in hepatocytes. In agreement with the findings in vitro, we found that the expression of miR-29 and the protein levels of p85α were inversely correlated in the liver of fasted mice. Overexpression of miR-29b reduced the insulin-induced phosphorylation of Akt in hepatocytes, suggesting that miR-29 could serve as a negative regulator of insulin signaling. Furthermore, we found that overexpression of miR-29 could attenuate the effect of AICAR on p85α expression. Taken together, our results indicated that activation of AMPK may enhance insulin signaling via downregulation of miR-29.