Stimulation of cloned human glucagon‐like peptide 1 receptor expressed in HEK 293 cells induces cAMP‐dependent activation of calcium‐induced calcium release

Abstract
The actions of glucagon-like peptide-1(7–36)amide (GLP-1(7–36)amide) on cellular signalling were studied in human embryonal kidney 293 (HEK 293) cells stably transfected with the cloned human GLP-1 receptor. The cloned GLP-1 receptor showed a single high-affinity binding site (Kd = 0.76 nM). Binding of GLP-1(7–36)amide stimulated cAMP production in a dose-dependent manner (EC50 = 0.015 nM) and caused an increase in the intracellular free Ca2+ concentration ([Ca2+]i). The latter effect reflected Ca2+-induced Ca2+ release and was suppressed by ryanodine. We propose that the ability of GLP-1(7–36)amide to increase [Ca2+]i results from sensitization of the ryanodine receptors by a protein kinase A dependent mechanism