TY - JOUR
T1 - Selected tetrapeptides lead to a GLP-1 release from the human enteroendocrine cell line NCI-H716
AU - Le Nevé, Boris
AU - Daniel, Hannelore
PY - 2011/2/25
Y1 - 2011/2/25
N2 - Enteroendocrine cells in the intestine sense the luminal contents and have been shown to respond to not only fatty acids, proteins, and monosaccharides but also artificial sweeteners and bitter compounds. Secretion of hormones such as CCK and GLP-1 from these cells is often associated with a rise in intracellular calcium concentration [Ca2+]i. The human NCI-H716 enteroendocrine cell line has been described as a proper model to study GLP-1 secretion in response to amino acids and protein hydrolysates. Here, we describe that NCI-H716 cells specifically respond to selective tetrapeptides such as tetra-glycine, tetra-alanine and Gly-Trp-Gly-Gly with a dose-dependent [Ca2+]i response and a GLP-1 secretion, whereas selected free amino acids, dipeptides, tripeptides and pentapeptides failed to elicit such a response. Hormone secretion was not associated with changes in cAMP levels in the cells. The calcium-dependence of hormone secretion appears to involve store-operated calcium channels (SOCCs), since the SOCC blocker 2-APB abolished both the [Ca2+]i response and GLP-1 release upon tetra-glycine stimulation. The nature of the sensor currently remains elusive, and no obvious common structural pattern in tetrapeptides eliciting GLP-1 secretion was identified. This tetrapeptide sensing in NCI-H716 cells may be underlying the effective stimulation of hormone secretion shown for various protein hydrolysates, and could involve a novel G-protein-coupled receptor (GPCR).
AB - Enteroendocrine cells in the intestine sense the luminal contents and have been shown to respond to not only fatty acids, proteins, and monosaccharides but also artificial sweeteners and bitter compounds. Secretion of hormones such as CCK and GLP-1 from these cells is often associated with a rise in intracellular calcium concentration [Ca2+]i. The human NCI-H716 enteroendocrine cell line has been described as a proper model to study GLP-1 secretion in response to amino acids and protein hydrolysates. Here, we describe that NCI-H716 cells specifically respond to selective tetrapeptides such as tetra-glycine, tetra-alanine and Gly-Trp-Gly-Gly with a dose-dependent [Ca2+]i response and a GLP-1 secretion, whereas selected free amino acids, dipeptides, tripeptides and pentapeptides failed to elicit such a response. Hormone secretion was not associated with changes in cAMP levels in the cells. The calcium-dependence of hormone secretion appears to involve store-operated calcium channels (SOCCs), since the SOCC blocker 2-APB abolished both the [Ca2+]i response and GLP-1 release upon tetra-glycine stimulation. The nature of the sensor currently remains elusive, and no obvious common structural pattern in tetrapeptides eliciting GLP-1 secretion was identified. This tetrapeptide sensing in NCI-H716 cells may be underlying the effective stimulation of hormone secretion shown for various protein hydrolysates, and could involve a novel G-protein-coupled receptor (GPCR).
KW - Calcium
KW - Nutrient sensing
KW - Store-operated calcium channels
UR - http://www.scopus.com/inward/record.url?scp=79951675071&partnerID=8YFLogxK
U2 - 10.1016/j.regpep.2010.10.010
DO - 10.1016/j.regpep.2010.10.010
M3 - Article
C2 - 21070823
AN - SCOPUS:79951675071
SN - 0167-0115
VL - 167
SP - 14
EP - 20
JO - Regulatory Peptides
JF - Regulatory Peptides
IS - 1
ER -