The role of Cox‐2 and prostaglandin E 2 receptor EP3 in pancreatic β‐cell death

What is it about?

Type 2 diabetes (T2D) is a complex disease involving pancreatic beta-cell failure and reduced beta-cell mass. Elevated plasma levels of glucose and lipids are often associated with the disease and lead to β-cell dysfunction and eventually death. In this report, we bring new evidence that palmitate, the abundant FFA in T2D patients, preferentially induces beta cell death by upregulating Cox2 and PGE2 receptor EP3 gene expression. Downregulation of the Cox2-EP3 pathway using specific siRNAs or pharmacological inhibitors significantly protected β-cells from FFA-induced cell death. Importantly these genes were found to be elevated in islets isolated from T2D individuals, providing a link between this disease and FFA-mediated β-cell dysfunction, and death. These findings provide the first direct evidence that EP3 activation contributes to β-cell demise in the setting of T2D and interfering with EP3 function could serve as a strategy for preserving β-cell mass.

Featured Image