ADP receptor P2Y13 induce apoptosis in pancreatic β-cells

Pancreatic β-cell loss represents a key factor in the pathogenesis of diabetes. Since the influence of purinergic signaling in β-cell apoptosis has not been much investigated, we examined the role of the ADP receptor P2Y13 using the pancreatic insulinoma-cell line MIN6c4 as a model system. Real time-PCR revealed high expression of the ADP receptors P2Y1 and P2Y13. Adding the ADP analogue, 2MeSADP, to MIN6c4 cells induced calcium influx/mobilization and inhibition of cAMP production by activation of P2Y1 and P2Y13, respectively. 2MeSADP reduced cell proliferation and increased Caspase-3 activity; both these effects could be fully reversed by the P2Y13 receptor antagonist MRS2211. We further discovered that blocking the P2Y13 receptor results in enhanced ERK1/2, Akt/PKB and CREB phosphorylation mechanisms involved in β-cell survival. These results indicate that P2Y13 is a proapoptotic receptor in β-cells as the P2Y13 receptor antagonist MRS2211 is able to protect the cells from ADP induced apoptosis.