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首页> 外文期刊>BMC Biotechnology >Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivo studies
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Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivo studies

机译：水稻中转基因人胰岛素样生长因子-I的降​​糖作用：体内外研究

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Background Human insulin-like growth factor-I (hIGF-I) is a growth factor which is highly resemble to insulin. It is essential for cell proliferation and has been proposed for treatment of various endocrine-associated diseases including growth hormone insensitivity syndrome and diabetes mellitus. In the present study, an efficient plant expression system was developed to produce biologically active recombinant hIGF-I (rhIGF-I) in transgenic rice grains. Results The plant-codon-optimized hIGF-I was introduced into rice via Agrobacterium -mediated transformation. To enhance the stability and yield of rhIGF-I, the endoplasmic reticulum-retention signal and glutelin signal peptide were used to deliver rhIGF-I to endoplasmic reticulum for stable accumulation. We found that only glutelin signal peptide could lead to successful expression of hIGF-I and one gram of hIGF-I rice grain possessed the maximum activity level equivalent to 3.2 micro molar of commercial rhIGF-I. In vitro functional analysis showed that the rice-derived rhIGF-I was effective in inducing membrane ruffling and glucose uptake on rat skeletal muscle cells. Oral meal test with rice-containing rhIGF-I acutely reduced blood glucose levels in streptozotocin-induced and Zucker diabetic rats, whereas it had no effect in normal rats. Conclusion Our findings provided an alternative expression system to produce large quantities of biologically active rhIGF-I. The provision of large quantity of recombinant proteins will promote further research on the therapeutic potential of rhIGF-I.
机译：背景技术人胰岛素样生长因子-1（hIGF-1）是与胰岛素高度相似的生长因子。它对于细胞增殖是必不可少的，并且已经被提议用于治疗各种与内分泌相关的疾病，包括生长激素不敏感综合症和糖尿病。在本研究中，开发了一种有效的植物表达系统，以在转基因水稻籽粒中产生具有生物活性的重组hIGF-1（rhIGF-1）。结果通过农杆菌介导的转化将植物密码子优化的hIGF-1引入水稻。为了增强rhIGF-1的稳定性和产量，使用内质网保留信号和谷蛋白信号肽将rhIGF-1递送至内质网以稳定积累。我们发现只有谷蛋白信号肽才能成功表达hIGF-1，一克hIGF-1稻谷具有的最大活性水平相当于商业rhIGF-1的3.2微摩尔。体外功能分析表明，源自水稻的rhIGF-I可有效诱导大鼠骨骼肌细胞膜起皱和葡萄糖摄取。用含大米的rhIGF-I进行的口服试验可急性降低链脲佐菌素诱导的糖尿病大鼠和祖克糖尿病大鼠的血糖水平，而对正常大鼠则无作用。结论我们的发现为生产大量具有生物活性的rhIGF-I提供了另一种表达系统。提供大量的重组蛋白将促进对rhIGF-1的治疗潜力的进一步研究。

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