Excessive secretion of glucagon, a functional insulin antagonist, significantly contributes to hyperglycemia. Glucagon exerts its physiological functions through activation of the glucagon receptor (GCGR). Inhibition of GCGR activity represents a potential therapeutic approach for reducing excess glucose production in diabetes mellitus. Aptamers are short DNA or RNA oligonucleotides evolved from systematic evolution of ligands by exponential enrichment (SELEX). Here, we have successfully selected a DNA aptamer against GCGR by cell-SELEX, which can specifically bind membrane protein of CHO-GCGR cells with a K _d of 52.7 ± 5.1 nM. Aptamer-mediated pull-down and gcgr knockdown assay verified that GCGR was the target of aptamer GR-3. Binding analysis revealed that GR-3 could recognize other cells with different affinity according to the level of GCGR protein expressed in these cells. Hepatic tissue imaging suggested that GR-3 could bind the cell membrane of hepatic tissues. With the advantages of small size, high binding affinity, good stability, lack of immunogenicity, and easy synthesis, aptamer GR-3 against GCGR can be a promising tool with the potential to attenuate hyperglycemia in diabetes mellitus.

中文翻译：

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通过细胞SELEX筛选和抗胰高血糖素受体的DNA适体。

胰高血糖素（一种功能性胰岛素拮抗剂）的过度分泌显着促成高血糖症。胰高血糖素通过激活胰高血糖素受体（GCGR）发挥其生理功能。抑制GCGR活性代表了减少糖尿病中过量葡萄糖产生的潜在治疗方法。适体是从配体通过指数富集（SELEX）系统进化而来的短DNA或RNA寡核苷酸。在这里，我们已经通过cell-SELEX成功地选择了一种抗GCGR的DNA适体，它可以与K _d特异性结合CHO-GCGR细胞的膜蛋白。为52.7±5.1nM。适体介导的下拉和gcgr击倒试验证实GCGR是适体GR-3的目标。结合分析显示，GR-3可以根据在这些细胞中表达的GCGR蛋白的水平识别其他具有不同亲和力的细胞。肝组织成像提示GR-3可以结合肝组织的细胞膜。具有体积小，结合亲和力高，稳定性好，缺乏免疫原性和易于合成的优点，针对GCGR的适体GR-3可以成为有希望的工具，具有减轻糖尿病中高血糖症的潜力。