Choi Kyung Jin, Hwang Jin Wook, Kim Se Hoon, Park Hyung Seo
Department of Physiology, College of Medicine, Konyang University, Daejeon 35365, Korea.
Myunggok Medical Research Institute, Konyang University, Daejeon 35365, Korea.
Korean J Physiol Pharmacol. 2022 May 1;26(3):219-225. doi: 10.4196/kjpp.2022.26.3.219.
Glucagon like peptide-1 (GLP-1) released from enteroendocine L-cells in the intestine has incretin effects due to its ability to amplify glucose-dependent insulin secretion. Promotion of an endogenous release of GLP-1 is one of therapeutic targets for type 2 diabetes mellitus. Although the secretion of GLP-1 in response to nutrient or neural stimuli can be triggered by cytosolic Ca elevation, the stimulus-secretion pathway is not completely understood yet. Therefore, the aim of this study was to investigate the role of reverse Na/Ca exchanger (rNCX) in Ca entry induced by muscarinic stimulation in NCI-H716 cells, a human enteroendocrine GLP-1 secreting cell line. Intracellular Ca was repetitively oscillated by the perfusion of carbamylcholine (CCh), a muscarinic agonist. The oscillation of cytosolic Ca was ceased by substituting extracellular Na with Li+ or NMG+. KB-R7943, a specific rNCX blocker, completely diminished CCh-induced cytosolic Ca oscillation. Type 1 Na/Ca exchanger (NCX) proteins were expressed in NCI-H716 cells. These results suggest that rNCX might play a crucial role in Ca entry induced by cholinergic stimulation in NCI-H716 cells, a GLP-1 secreting cell line.
从肠道内分泌L细胞释放的胰高血糖素样肽-1（GLP-1）具有肠促胰岛素效应，因为它能够增强葡萄糖依赖性胰岛素分泌。促进内源性GLP-1释放是2型糖尿病的治疗靶点之一。尽管GLP-1对营养或神经刺激的分泌可由胞质Ca升高触发，但刺激-分泌途径尚未完全清楚。因此，本研究的目的是探讨反向钠/钙交换器（rNCX）在毒蕈碱刺激诱导的人肠内分泌GLP-1分泌细胞系NCI-H716细胞Ca内流中的作用。通过灌注毒蕈碱激动剂氨甲酰胆碱（CCh）使细胞内Ca反复振荡。用Li+或NMG+替代细胞外Na可使胞质Ca振荡停止。特异性rNCX阻滞剂KB-R7943完全消除了CCh诱导的胞质Ca振荡。1型钠/钙交换器（NCX）蛋白在NCI-H716细胞中表达。这些结果表明，rNCX可能在GLP-1分泌细胞系NCI-H716细胞中胆碱能刺激诱导的Ca内流中起关键作用。
