Glucagon-like peptide 1 potentiates glucotoxicity-diminished insulin secretion via stimulation of cAMP-PKA signaling in INS-1E cells and mouse islets

► GLP-1 increased glucose-stimulated insulin secretion under glucotoxic conditions. ► GLP-1 preferentially stimulates PKA as a result from elevation of cAMP. ► The GLP-1 action was blocked by the PKA inhibitor Rp-cAMPS. ► GLP-1 failed to potentiate insulin secretion in the presence of the PKA agonist. ► Knockdown or maximally activation of Epac2 does not interfere with GLP-1 actions.