Endocrine Abstracts

Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are hormones secreted from enteroendocrine L cells following a meal that play a key role in regulating insulin secretion and glucose metabolism. Enteroendocrine L cells express calcium-sensing receptors (CaSRs), which serve as a physiological nutrient sensor for the release of hormones from the gastrointestinal tract. While calcium is the primary ligand for CaSR, its activity can also be controlled by amino acids and polyamines. Therefore, in human enteroendocrine L (NCI-H716) cells, we investigated the effects of L-arginine and agmatine, a naturally occurring polyamine generated from L-arginine, on GLP-1 and Pyy secretion, along with the involvement of CaSR in this effect. To investigate the effect of agmatine and L-arginine on GLP-1 and Pyy secretion, NCI-H716 cells were exposed to different concentrations of agmatine and L-arginine (20 mM and 40 mM), and GLP-1 and Pyy levels were measured. NPS 2143 and R568, which are negative and positive allosteric modulators of calcium-sensing receptors (CaSR), respectively, were also used to study the role of CaSR in hormone release. CaSR immunoreactivity and the second messengers (Ca⁺² and cAMP) that may mediate GLP-1 and Pyy release were also examined. Agmatine and L-arginine alone at 20 mM and 40 mM did not lead to significant GLP-1 and Pyy secretion. However, when combined with NPS 2143, there was a decrease in GLP-1 and Pyy levels. The cAMP level was decreased in the 40 mM agmatine + NPS 2143 group, while it was increased in the group treated with 40 mM agmatine + R568. Additionally, 40 mM L-arginine led to an increase in intracellular calcium concentration, while NPS 2143 reduced it. CaSR immunoreactivity was not different between groups. As a result, it was observed that GLP-1 and Pyy secretion was not induced by L-arginine or agmatine in NCI-H716 cells. Interestingly, NPS 2143 administration caused changes in hormone and cAMP/calcium levels, supporting the idea that CaSRs may be involved in GLP-1 and Pyy secretion in response to L-arginine and agmatine.

Key Words: L-arginine, Agmatine, GLP-1, Pyy, CaSR, NCI-H716 cell line, NPS 2143, R568, Ca⁺², cAMP.