Diabetologia:新型胰高血糖素样肽-1受体抗体的开发和特征

2018-04-12 MedSci MedSci原创

胰高血糖素样肽-1(GLP-1)通过与胰腺β细胞上的GLP-1受体(GLP1R)结合来增强葡萄糖依赖性胰岛素分泌。GLP-1模拟物在临床上用于治疗2型糖尿病,尽管有显著的疗效,但GLP-1的一些临床效果的机制仍不清楚,特别是在胰腺外的组织中。近日,国际杂志 《Diabetologia》上在线发表一项关于新型胰高血糖素样肽-1受体抗体的开发和特征的研究。 使用天然噬菌体展示选择策略来分离与G

胰高血糖素样肽-1(GLP-1)通过与胰腺β细胞上的GLP-1受体(GLP1R)结合来增强葡萄糖依赖性胰岛素分泌。GLP-1模拟物在临床上用于治疗2型糖尿病,尽管有显著的疗效,但GLP-1的一些临床效果的机制仍不清楚,特别是在胰腺外的组织中。近日,国际杂志 《Diabetologia》上在线发表一项关于新型胰高血糖素样肽-1受体抗体的开发和特征的研究。 使用天然噬菌体展示选择策略来分离与GLP1R结合的单链可变片段(ScFv)。将具有最高亲和力的ScFv Glp1R0017转化为人IgG1并进一步研究其特征。研究在许多检测中评估了体外拮抗活性:在GLP1R过表达细胞系中,进行基于cAMP的同质时间分辨荧光检测,在INS-1 832/3细胞中,进行活细胞cAMP成像测定和的胰岛素分泌测定。在小鼠胰腺的免疫染色中进一步测试了Glp1R0017,并且在C57 / Bl6小鼠中通过IPGTT和OGTT评估了体内Glp1R0017阻断GLP1R的能力。 研究从天然抗体噬菌体展示文库中选择抗GLP1R的抗体。单克隆抗体Glp1R0017拮抗小鼠,人,大鼠,食蟹猴和狗GLP1R。这种拮抗活性对GLP

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    2018-04-14 hbwxf
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