Dept. of Chemistry - BMC, Uppsala University, SE-751 23 Uppsala, Sweden.
Discovery Sciences, R&D, AstraZeneca, Pepparedsleden 1, 431 50 Mölndal, Sweden.
Bioorg Med Chem Lett. 2020 Jul 1;30(13):127208. doi: 10.1016/j.bmcl.2020.127208. Epub 2020 Apr 20.
Proinsulin C-peptide has previously been proposed to interact with a G-protein coupled receptor (GPCR), specifically the orphan receptor GPR146. To investigate the potential of C-peptide in treating complications of diabetes, such as kidney damage, it is necessary to understand its mode of action. We used CHO-K1 cells expressing human GPR146 to study human and murine C-peptide in dynamic mass redistribution and GPCR β-arrestin assays, as well as with fluorescence confocal microscopy. Neither assay revealed any significant intracellular response to C-peptide at concentrations of up to 33 µM. We observed no internalisation of C-peptide by fluorescence microscopy. Our results do not support GPR146 as the receptor for C-peptide, but suggest that further investigations of the mode of action of C-peptide should be undertaken.
胰岛素原 C 肽先前被提议与 G 蛋白偶联受体（GPCR）相互作用，特别是孤儿受体 GPR146。为了研究 C 肽在治疗糖尿病并发症（如肾脏损伤）方面的潜力，有必要了解其作用模式。我们使用表达人 GPR146 的 CHO-K1 细胞，在动态质量重分布和 GPCR β-arrestin 测定中研究人和鼠的 C 肽，以及使用荧光共焦显微镜。在高达 33µM 的浓度下，这两种测定都没有显示出 C 肽对细胞内的任何显著反应。我们通过荧光显微镜观察到 C 肽没有内化。我们的结果不支持 GPR146 作为 C 肽的受体，但表明应该进一步研究 C 肽的作用模式。
