INS and pancreatic insulinoma: Likewise, in the mouse insulinoma βTC6 cells and human islets, GLP-1R-mediated insulin secretion by exendin (Ex)-4 (a peptide agonist of GLP-1R) treatment was inhibited in a dose-dependent manner by both synthetic (ACEA) and endogenous (2-AG and AEA) CB1R agonists, indicative of negative EC actions in incretin-mediated insulin secretion by activated CB1R. The underlying mechanism for this likely is suppression of Ex-4-evoked increases in AC activity and reduced intracellular cAMP.