The effect of L-arginine and Agmatine on GLP-1 and PYY Secretion in human enteroendocrine NCI-H716 Cells : The role of Calcium sensing receptors

Agmatine is a natural polyamine produced from L-arginine by arginine decarboxylase and is abundant in foods. One of the most significant effects of glucagon like peptide-1 (GLP-1) and peptide YY (PYY) hormones released from enteroendocrine L cells following food intake is their regulation of insulin secretion after meals, which helps in maintaining blood glucose levels. In this study, the effects of agmatine and L-arginine on the secretion of GLP-1 and PYY were investigated using NCI-H716 cells, a human enteroendocrine L cell line. The cells were incubated with different concentrations of agmatine and L-arginine (20 mM and 40 mM) for 2 hours, and the secretion of GLP-1 and PYY was measured. Additionally, negative and positive allosteric modulators of CaSR, NPS 2143 and R568, respectively, were applied in combination with these substances to explore the role of calcium-sensing receptors (CaSR) in hormone secretion. Although 20 and 40 mM doses of agmatine and L-arginine alone did not cause GLP-1 and PYY secretion, their co- administration with NPS 2143 resulted in a decrease in GLP-1 and PYY secretion. This result suggested that CaSR might be a mediator receptor in the secretion of GLP-1 and PYY. In tests to identify intracellular second messengers involved in the release of GLP-1 and PYY from NCI-H716 cells, cAMP levels were shown to drop in the 40 mM agmatine + NPS 2143 group and to increase in the 40 mM agmatine + R568 group. It was found that intracellular calcium density increased with 40 mM L-arginine and decreased when administered with NPS 2143. There was no difference in the levels of CaSR immunoreactivity between the groups. In conclusion, human enteroendocrine L-cell line NCI-H716 cells treated with 20 and 40 mM agmatine and L-arginine do not significantly increase hormone secretion, whereas NPS 2143 administration causes alterations in both hormone and cAMP/calcium levels. In conclusion, 20 and 40 mM doses of agmatine and L-arginine in NCI-H716 cells, which are the human enteroendocrine L-cell line, do not cause a significant hormone secretion, while changes occur in both hormone and cAMP/calcium levels due to NPS 2143 application. It supports the idea that CaSRs have a role in the secretion of GLP-1 and PYY.