Secretion of GLP-1 from intestinal L-cells is dependent on a rise in cytosolic calcium which, in turn, is stimulated by glucose (requires the GLUT2 glucose transporter), fatty acids (especially monounsaturated fatty acids, requires the GPR120 and GPR40 receptors), insulin, leptin, gastrin-releasing peptide, cholinergic transmitters (requires M1 and M2 muscarinic receptors), amino acids (requires mitogen activated protein kinase pathway), beta-adrenergic transmitters, and peptidergic transmitters. The exact mechanisms controlling secretion have not been elucidated.
The G-protein coupled receptor Alpha-Gustducin is present in human intestinal L cells. The sweet taste receptors TIR2 and TIR3 are also detectable. Experiments in mice lacking Alpha-Gustducin show that it is required for stimulation of GLP-1 secretion by glucose.