Research Unit of Biomedicine, Medical Research Center, Faculty of Medicine, University of Oulu, Oulu University Hospital, Oulu, Finland.
Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland.
Peptides. 2020 Dec;134:170419. doi: 10.1016/j.peptides.2020.170419. Epub 2020 Sep 28.
Glucagon like peptide-1 (GLP-1) is an incretin hormone, secreted from L-cells of distal ileum and colon in response to nutrient ingestion in human. GLP-1 plays a major role in gut motility, appetite regulation, and insulin secretion. Dipeptidyl peptidase-4 (DPP4), a serine peptidase, cleaves N-terminal dipeptides of GLP-1, rendering it inactive and responsible for its short half-life. DPP4 is widely expressed in numerous tissues in a membrane bound or soluble form. The enteroendocrine cell lines STC-1 and GLUTag are extensively used as models for in vitro studies, however, the basic parallel characterization between these cell lines is still missing. Previously, we demonstrated that these cell lines exhibit different responses to α-linolenic acid (αLA)-induced GLP-1 secretion. Therefore, we examined the basal and stimulated GLP-1 and DPP4 secretion between the two cell lines. GPR120 and GPR40 are known to bind long chain fatty acids. We found that STC-1 cells secreted significantly more basal and αLA-induced GLP-1 than GLUTag cells. In addition, STC-1 secreted DPP4 and expressed higher amounts of DPP4 and GPR120 than GLUTag cells, while GLUTag cells expressed higher GPR40 protein levels than STC-1 cells. Interestingly, the secreted soluble DPP4 did not change the active GLP-1 concentrations in the buffer group, and only 5.5 % of GLP-1 was degraded in the αLA stimulated group. These results suggested that STC-1 cells have a higher potential to secrete GLP-1 and DPP4 than GLUTag cells, and the membrane bound DPP4 may play a more significant role in the inactivation of GLP-1 secretion.
胰高血糖素样肽-1（GLP-1）是一种肠促胰岛素激素，在人类中，它从回肠和结肠的 L 细胞响应营养物质摄入而分泌。GLP-1 在肠道动力、食欲调节和胰岛素分泌中发挥重要作用。二肽基肽酶-4（DPP4）是一种丝氨酸肽酶，可切割 GLP-1 的 N 端二肽，使其失活，并导致其半衰期短。DPP4 广泛表达于许多组织中，以膜结合或可溶性形式存在。肠内分泌细胞系 STC-1 和 GLUTag 被广泛用作体外研究的模型，然而，这两种细胞系之间的基本平行特征仍然缺失。以前，我们证明这些细胞系对 α-亚麻酸（αLA）诱导的 GLP-1 分泌表现出不同的反应。因此，我们检查了这两种细胞系之间的基础和刺激的 GLP-1 和 DPP4 分泌。GPR120 和 GPR40 已知结合长链脂肪酸。我们发现，STC-1 细胞分泌的基础和 αLA 诱导的 GLP-1 明显多于 GLUTag 细胞。此外，STC-1 细胞分泌的 DPP4 量和表达的 DPP4 和 GPR120 量均高于 GLUTag 细胞，而 GLUTag 细胞表达的 GPR40 蛋白水平高于 STC-1 细胞。有趣的是，分泌的可溶性 DPP4 并未改变缓冲液组中活性 GLP-1 的浓度，并且在 αLA 刺激组中仅 5.5%的 GLP-1 被降解。这些结果表明，STC-1 细胞比 GLUTag 细胞具有更高的分泌 GLP-1 和 DPP4 的潜力，并且膜结合的 DPP4 可能在 GLP-1 分泌的失活中发挥更重要的作用。
