Anti-apoptotic effects of arachidonic acid and prostaglandin E-2 in pancreatic beta-cells

Background/ Aims: The polyunsaturated fatty acid arachidonic acid ( AA) has been implicated in beta- cell defence mechanisms and prostaglandin ( PG) products of cyclooxygenase ( COX) 2 action confer resistance to alloxan- induced apoptosis in insulin- secreting RIN cells. We have now investigated the antiapoptotic effects of AA and its metabolite, PGE(2), in the MIN6 mouse insulin- secreting beta-cell line and mouse islets. Methods: Apoptosis was determined in MIN6 beta-cell and mouse islet extracts by measurement of capase- 3 activity, and COX2 mRNA levels were quantified by real- time RT- PCR. Results: Exposure of MIN6 cells to AA ( 3.1- 12.5 mu M) caused concentration-dependent reductions in apoptosis, and similar results were obtained when endogenous AA levels were elevated in cytosolic phospholipase A (2)-overexpressing MIN6 cells. 25mM glucose caused both a significant up- regulation of MIN6 cell COX2 mRNA levels and a decrease in apoptosis. Inhibition of MIN6 cell COX2 activity with a selective inhibitor, NS- 398 ( 10- 100 mu M), increased apoptosis and exogenous PGE(2) ( 0.2- 5 mu M) reduced NS-398- induced apoptosis in a concentration- dependent manner. The protective effects of AA and PGE(2) were also observed in primary mouse islets. Conclusion: These data show that AA and its COX2- generated metabolite, PGE(2), can protect beta-cells from apoptosis.