The increased secretion of glucagon-like peptide-1 (GLP-1) after Roux-en-Y gastric bypass (RYGB) is regarded as the main reason for the improvement of blood glucose. However, the single-nucleotide polymorphisms (SNPs) of GLP-1 Receptor (GLP1R) impair receptor function, subsequently affecting β cell insulin secretion function, ultimately affecting the efficacy of RYGB. In this study, we revealed that two SNPs in GLP1R gene, rs3765467 and rs10305492, could significantly reduce the insulin secreted by β cells and the cyclic AMP concentration, whereas promote β cell apoptosis. Under high glucose exposure, rs3765467 and rs10305492 impaired β cell secretion of insulin and β cell viability in the same way; in other words, GLP1R rs3765467 and rs10305492 exert an effect on pancreatic β cell glucose-stimulated insulin secretion. Moreover, GLP-1 antagonist Exendin (9-39) further enhanced, whereas GLP-1 agonist Exendin-4 partially attenuated the effects of SNPs on the functions and apoptosis of β cells. In conclusion, the rs3765467 and rs10305492 SNPs in GLP1R show to exert a critical effect on regulating insulin secretory capacity of β cells and β cell mass. Through leading to the dysfunction and apoptosis of β cells, GLP1R rs3765467 and rs10305492 might also impair GLP-1 interaction with GLP1R, therefore attenuating the therapeutic effect of RYGB.

中文翻译：

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GLP1R单核苷酸多态性rs3765467和rs10305492通过GLP-1影响β细胞胰岛素分泌能力和细胞凋亡。

Roux-en-Y胃旁路手术（RYGB）后胰高血糖素样肽1（GLP-1）分泌增加被认为是改善血糖的主要原因。但是，GLP-1受体（GLP1R）的单核苷酸多态性（SNP）损害受体功能，随后影响β细胞胰岛素分泌功能，最终影响RYGB的疗效。在这项研究中，我们揭示了GLP1R基因中的两个SNP，即rs3765467和rs10305492，可以显着减少β细胞分泌的胰岛素和环状AMP浓度，而促进β细胞凋亡。在高葡萄糖暴露下，rs3765467和rs10305492以相同的方式损害胰岛素的β细胞分泌和β细胞活力。换句话说，GLP1Rrs3765467和rs10305492对胰腺β细胞葡萄糖刺激的胰岛素分泌产生影响。此外，GLP-1拮抗剂Exendin（9-39）进一步增强，而GLP-1激动剂Exendin-4则部分减弱了SNP对β细胞功能和凋亡的影响。总之，GLP1R中的rs3765467和rs10305492 SNPs对调节β细胞和β细胞的胰岛素分泌能力起着关键作用。GLP1R rs3765467和rs10305492通过导致β细胞功能障碍和凋亡，也可能削弱GLP-1与GLP1R的相互作用，从而削弱RYGB的治疗作用。