Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Global Drug Discovery, Novo Nordisk A/S, Måløv, Denmark.
Am J Physiol Cell Physiol. 2022 Jun 1;322(6):C1260-C1269. doi: 10.1152/ajpcell.00345.2021. Epub 2022 Apr 20.
Exocrine glands in the submucosa of the proximal duodenum secrete alkaline fluid containing mucus to protect the intestinal mucosa from acidic stomach contents. These glands, known as Brunner's glands, express high glucagon-like peptide 1 receptor (GLP-1R) levels. Previous studies have suggested that activation of the GLP-1R induces expression of barrier protective genes in Brunner's glands. Still, the lack of a viable in vitro culture of Brunner's glands has hampered additional studies of the functional consequences of GLP-1R activation. In this study, we established a procedure to isolate and culture cells derived from murine Brunner's glands. The isolated glandular cells retained functional GLP-1R expression in culture, making this in vitro system suitable for the study of GLP-1R activation. We found that cells derived from the Brunner's glands of mice pretreated with semaglutide contained significantly more mucus compared with Brunner's glands from vehicle-treated mice. Our data suggest a protective intestinal response upon semaglutide treatment, but further studies are required to leverage the full potential of cultured Brunner's gland cells.
十二指肠近端黏膜下的外分泌腺分泌含有黏液的碱性液体,以保护肠黏膜免受酸性胃内容物的侵害。这些腺称为 Brunner 腺,表达高水平的胰高血糖素样肽 1 受体 (GLP-1R)。先前的研究表明,GLP-1R 的激活诱导 Brunner 腺中屏障保护基因的表达。然而,由于缺乏可行的 Brunner 腺体外培养方法,进一步研究 GLP-1R 激活的功能后果受到了阻碍。在这项研究中,我们建立了一种分离和培养来自小鼠 Brunner 腺细胞的方法。分离的腺细胞在培养中保留了功能性的 GLP-1R 表达,使该体外系统适合研究 GLP-1R 的激活。我们发现,与 vehicle 处理的小鼠的 Brunner 腺相比,用司美格鲁肽预处理的小鼠的 Brunner 腺来源的细胞中含有明显更多的黏液。我们的数据表明,司美格鲁肽治疗后会出现保护性的肠道反应,但需要进一步的研究来充分利用培养的 Brunner 腺细胞的潜力。