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首页> 外文期刊>International Journal of General Medicine >Possible hypoglycemic action of SX-fraction targeting insulin signal transduction pathway
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Possible hypoglycemic action of SX-fraction targeting insulin signal transduction pathway

机译：SX级分靶向胰岛素信号转导途径的可能的降血糖作用

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Background: SX-fraction (SXF) is a bioactive glycoprotein with hypoglycemic activity that has been demonstrated in our pilot clinical study. However, how it would actually work in diabetic patients remains unclear. To explore such a mechanism, the effects of SXF on the insulin signal transduction pathway were investigated using skeletal muscle L6 cells in vitro.Methods: L6 cells were first differentiated to myotubes expressing several biochemical parameters that were examined in this study. Myotubes were exposed to a high concentration (35 mM) of glucose (Glc) alone or in combination with SXF or insulin for 24 hours. Possible effects of these agents on activities of insulin receptor (IR), IR substrate 1 (IRS-1), and Akt, which are key elements involved in the signal pathway, were assessed using enzyme-linked immunosorbent assay (ELISA). Any changes in Glc uptake were also determined.Results: High Glc indeed led to inactivation of IR, IRS-1, and subsequent Akt in myotubes, indicating an interruption of the signal pathway. However, such inactivation was reversed or reactivated by SXF, presumably aiding the occurrence of successive signaling events. Measurement of Glc uptake to assess the outcome of this signaling cascade showed that high Glc decreased Glc uptake (interfering with the signal pathway), but SXF was capable of overcoming such a suppressive effect, resulting in the increased Glc uptake. Insulin was used as a positive control in this study and all results were nearly compatible to those obtained from SXF.Conclusion: The present study suggests that SXF may specifically target the insulin signal pathway, and, in particular, the IR and IRS-1 therein that trigger the subsequent signaling events. As a result, SXF could activate such an impaired signal pathway through high Glc or under a hyperglycemic milieu, thereby ultimately facilitating Glc uptake. This may then account for possible hypoglycemic action of SXF.
机译：背景：SX馏分（SXF）是一种具有降血糖活性的生物活性糖蛋白，已在我们的临床试验研究中得到证实。但是，目前尚不清楚它在糖尿病患者中的实际作用如何。为了探索这种机制，在体外用骨骼肌L6细胞研究了SXF对胰岛素信号转导途径的影响。方法：首先将L6细胞分化为表达几种生化参数的肌管，本研究对此进行了研究。肌管单独或与SXF或胰岛素一起暴露于高浓度（35 mM）的葡萄糖（Glc）中24小时。使用酶联免疫吸附测定（ELISA）评估了这些试剂对胰岛素受体（IR），IR底物1（IRS-1）和Akt的活性的可能作用，这些受体是信号通路中的关键要素。结果：高Glc确实导致肌管中IR，IRS-1和随后的Akt失活，表明信号通路中断。但是，这种失活被SXF逆转或重新激活，大概有助于后续信号事件的发生。测量Glc摄取以评估该信号级联反应的结果表明，高Glc降低了Glc摄取（干扰信号途径），但是SXF能够克服这种抑制作用，从而导致Glc摄取增加。胰岛素被用作本研究的阳性对照，所有结果均与从SXF获得的结果几乎相符。结论：本研究表明SXF可能特异性靶向胰岛素信号途径，尤其是其中的IR和IRS-1触发后续的信令事件。结果，SXF可以通过高Glc或在血糖过高的环境下激活这种受损的信号途径，从而最终促进Glc的吸收。然后，这可以解释SXF可能的降血糖作用。

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