Research Unit of Biomedicine and Internal Medicine, Biocenter of Oulu, Medical Research Center, University of Oulu, Aapistie 5, 90220, Oulu, Finland.
Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, 60572, Poznań, Poland.
Pflugers Arch. 2024 Oct;476(10):1613-1621. doi: 10.1007/s00424-024-02996-z. Epub 2024 Jul 29.
Glucagon-like peptide (GLP)-1 is a hormone released by enteroendocrine L-cells after food ingestion. L-cells express various receptors for nutrient sensing including G protein-coupled receptors (GPRs). Intestinal epithelial cells near the lumen have a lower O tension than at the base of the crypts, which leads to hypoxia in L-cells. We hypothesized that hypoxia affects nutrient-stimulated GLP-1 secretion from the enteroendocrine cell line STC-1, the most commonly used model. In this study, we investigated the effect of hypoxia (1% O) on alpha-linolenic acid (αLA) stimulated GLP-1 secretion and their receptor expressions. STC-1 cells were incubated for 12 h under hypoxia (1% O) and treated with αLA to stimulate GLP-1 secretion. 12 h of hypoxia did not change basal GLP-1 secretion, but significantly reduced nutrient (αLA) stimulated GLP-1 secretion. In normoxia, αLA (12.5 μM) significantly stimulated (~ 5 times) GLP-1 secretion compared to control, but under hypoxia, GLP-1 secretion was reduced by 45% compared to normoxia. αLA upregulated GPR120, also termed free fatty acid receptor 4 (FFAR4), expressions under normoxia as well as hypoxia. Hypoxia downregulated GPR120 and GPR40 expression by 50% and 60%, respectively, compared to normoxia. These findings demonstrate that hypoxia does not affect the basal GLP-1 secretion but decreases nutrient-stimulated GLP-1 secretion. The decrease in nutrient-stimulated GLP-1 secretion was due to decreased GPR120 and GPR40 receptors expression. Changes in the gut environment and inflammation might contribute to the hypoxia of the epithelial and L-cells.
胰高血糖素样肽 (GLP)-1 是一种在进食后由肠内分泌 L 细胞释放的激素。L 细胞表达多种用于营养感应的受体，包括 G 蛋白偶联受体 (GPR)。靠近腔的肠上皮细胞的 O 张力比在隐窝底部低，导致 L 细胞缺氧。我们假设缺氧会影响肠内分泌细胞系 STC-1 对营养刺激的 GLP-1 分泌，STC-1 是最常用的模型。在这项研究中，我们研究了缺氧 (1% O) 对 α-亚麻酸 (αLA) 刺激 GLP-1 分泌及其受体表达的影响。STC-1 细胞在缺氧 (1% O) 下孵育 12 小时，并接受 αLA 刺激以刺激 GLP-1 分泌。12 小时的缺氧不会改变基础 GLP-1 分泌，但显著降低营养 (αLA) 刺激的 GLP-1 分泌。在常氧条件下，αLA (12.5 μM) 与对照相比显著刺激 (~5 倍) GLP-1 分泌，但在缺氧条件下，与常氧相比，GLP-1 分泌减少了 45%。αLA 在常氧和缺氧条件下均上调 GPR120 的表达，也称为游离脂肪酸受体 4 (FFAR4)。与常氧相比，缺氧分别下调 GPR120 和 GPR40 表达 50%和 60%。这些发现表明，缺氧不会影响基础 GLP-1 分泌，但会减少营养刺激的 GLP-1 分泌。营养刺激的 GLP-1 分泌减少是由于 GPR120 和 GPR40 受体表达减少所致。肠道环境和炎症的变化可能导致上皮细胞和 L 细胞缺氧。
