Signaling through A adenosine receptor specifically prevent pancreatic β-cells (PBCs) loses under diabetogenic conditions. However, signaling mediators of this receptor in PBCs remained unidentified. Thus, we aimed to investigate the possible involvement of PKA/Akt/IPP-1/CREB pathway in MIN6 β-cells. In addition, we investigated IPP-1 role in A receptor signaling pathway. The expression of A receptor in MIN6 cell line was evaluated by RT-PCR and its functionality confirmed by quantification of cAMP in response to the CGS 21680, an A receptor agonist. MTT and Brdu assays were used to evaluate cell viability and proliferation, respectively. PKA activity and insulin release were evaluated using ELISA methods. P-Akt/Akt, p-IPP-1/IPP-1, and p-CREB/CREB levels were assessed using western blotting. IPP-1 knock down assessments was performed using specific siRNA. Our result revealed that MIN6 cells express A receptor which actively increased cAMP levels (with EC = 2.41 µM) and PKA activity. Activation of this receptor increased cell viability, proliferation and insulin release. Moreover, we mentioned A receptor stimulation increased p-Akt, p-IPP-1, and p-CREB levels in dose (max at 10 µM of CGS 21680) and time (max at 30 min after CGS 21680 treatment) dependent manner. Interestingly, herein, we found in IPP-1 knocked down cells, A receptor failed to activate Akt and CREB. Altogether, we mentioned that in MIN6 cells A receptor increase cell viability, proliferation and insulin release through PKA/Akt/IPP-1/CREB signaling pathway. In addition, we conclude A receptor signaling through this pathway is dependent to activation of IPP-1.