Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Novo Nordic Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Am J Physiol Gastrointest Liver Physiol. 2020 May 1;318(5):G980-G987. doi: 10.1152/ajpgi.00062.2020. Epub 2020 Apr 20.
Glucagon-like peptide (GLP)-1 and -2-secreting L cells have been shown to express the bile acid receptor Takeda G protein-receptor-5 (TGR5) and increase secretion upon receptor activation. Previous studies have explored GLP-1 secretion following acute TGR5 activation, but chronic activation and GLP-2 responses have not been characterized. In this study, we aimed to investigate the consequences of pharmacological TGR5 receptor activation on L cell hormone production in vivo using the specific TGR5 agonist RO5527239 and the GLP-2 receptor knockout mouse. Here, we show that ) TGR5 receptor activation led to increased GLP-1 and GLP-2 content in the colon, which ) was associated with an increased small intestinal weight that ) was GLP-2 dependent. Additionally, we report that TGR5-mediated gallbladder filling occurred independently of GLP-2 signaling. In conclusion, we demonstrate that pharmacological TGR5 receptor activation stimulates L cells, triggering GLP-2-dependent intestinal adaption in mice. Using the specific Takeda G protein-receptor-5 (TGR5) agonist RO5527239 and GLP-2 receptor knockout mice, we show that activation of TGR5 led to the increase in colonic GLP-1 and GLP-2 concomitant with a GLP-2 dependent growth response in the proximal portion of the small intestine.
胰高血糖素样肽 (GLP)-1 和 -2 分泌细胞已被证明表达胆汁酸受体 Takeda G 蛋白受体-5 (TGR5)，并且在受体激活时增加分泌。先前的研究已经探索了急性 TGR5 激活后 GLP-1 的分泌，但尚未对慢性激活和 GLP-2 反应进行表征。在这项研究中，我们旨在使用特异性 TGR5 激动剂 RO5527239 和 GLP-2 受体敲除小鼠研究药理学 TGR5 受体激活对体内 L 细胞激素产生的影响。在这里，我们表明）TGR5 受体激活导致结肠中 GLP-1 和 GLP-2 含量增加，这）与小肠重量增加有关，这）是 GLP-2 依赖性的。此外，我们报告 TGR5 介导的胆囊充盈发生独立于 GLP-2 信号。总之，我们证明药理学 TGR5 受体激活刺激 L 细胞，触发小鼠中的 GLP-2 依赖性肠道适应。使用特异性 Takeda G 蛋白受体-5 (TGR5) 激动剂 RO5527239 和 GLP-2 受体敲除小鼠，我们表明 TGR5 的激活导致结肠中 GLP-1 和 GLP-2 的增加，同时近端小肠出现 GLP-2 依赖性生长反应。
