Insulin upregulates betatrophin expression via PI3K/Akt pathway.
Insulin upregulates betatrophin expression via PI3K/Akt pathway.
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胰岛素通过 PI3K/Akt 途径上调 betatropin 表达
DOI：
10.1038/s41598-017-06052-y
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发表时间：
2017-07-17
影响因子：
4.6
通讯作者：
Yu X
中科院分区：
文献类型：
--
作者：
Lu P;Chen X;Zhang Z;Zhang J;Yang Y;Liu Z;Xie J;Shao S;Zhou X;Hu S;He W;Zhao J;Yu X
Betatrophin被认为是由胰岛素抵抗（IR）诱导的肝脏产生的激素。然而，IR如何调节betatrophin的表达仍然是未知的。为探讨胰岛素抵抗（IR）对betatrophin表达的影响及其分子机制，采用体外培养的人肝细胞L02建立6种IR模型，分别用肿瘤坏死因子-α（TNF-α）、白细胞介素-1 β（IL-1β）、地塞米松（Dexamethasone，Dexameth这些结果表明，它是胰岛素，而不是IR，促进betatrophin的表达。同时，PI 3 K/Akt途径被胰岛素激活，并被上述引起IR的药物抑制。胰岛素上调的betatrophin表达被PI 3 K/Akt抑制剂和IR抑制，表明胰岛素上调和IR通过PI 3 K/Akt途径减少betatrophin的产生。一致地，在小鼠中的胰岛素治疗剂量依赖性地上调betatrophin水平，并且在IR小鼠中施用二甲双胍也刺激betatrophin产生，因为已发表的研究显示二甲双胍改善PI 3 K/Akt途径和IR。在人类中，与未接受胰岛素治疗的患者相比，在接受胰岛素治疗的2型糖尿病患者中血清betatrophin水平升高。结论：胰岛素通过PI 3 K/Akt途径促进betatrophin的分泌，IR可能起相反的作用。
Betatrophin is regarded as a liver-produced hormone induced by insulin resistance (IR). However, it remains largely unknown how IR regulates betatrophin expression. To study whether IR could regulate betatrophin expression and the corresponding molecular mechanisms, betatrophin levels were examined in 6 in vitro IR models which were established using human hepatocytes L02 with different agents, including tumor necrosis factor-α, interleukin-1β, dexamethasone, palmitate, high glucose and insulin and betatrophin levels were elevated only in the insulin group. These results suggest that it is insulin, not IR that promotes betatrophin expression. In the meantime, PI3K/Akt pathway was activated by insulin and suppressed by above agents that caused IR. Insulin-upregulated betatrophin expression was suppressed by PI3K/Akt inhibitors and IR, suggesting that insulin upregulates and IR decreases betatrophin production through PI3K/Akt pathway. Consistently, the treatment of insulin in mice dose-dependently upregulated betatrophin levels, and the administration of metformin in IR mice also stimulated betatrophin production since published study showed metformin improved PI3K/Akt pathway and IR. In humans, compared with those without insulin treatment, serum betatrophin levels were increased in type 2 diabetic patients with insulin treatment. In conclusion, insulin stimulates betatrophin secretion through PI3K/Akt pathway and IR may play an opposite role.
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