Background/Aims: The polyunsaturated fatty acid arachidonic acid (AA) has been implicated in β-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 anti-apoptotic effects of AA and its metabolite, PGE2, in the MIN6 mouse insulin-secreting β-cell line and mouse islets. Methods: Apoptosis was determined in MIN6 β-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 (3.1-12.5µM) caused concentration-dependent reductions in apoptosis, and similar results were obtained when endogenous AA levels were elevated in cytosolic phospholipase A2-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 (10-100µM), increased apoptosis and exogenous PGE2 (0.2-5µM) reduced NS-398-induced apoptosis in a concentration-dependent manner. The protective effects of AA and PGE2 were also observed in primary mouse islets. Conclusion: These data show that AA and its COX2-generated metabolite, PGE2, can protect β-cells from apoptosis.

Keywords:
β-cells, Caspase-3, Apoptosis, Arachidonic acid, Prostaglandin E2
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© 2007 S. Karger AG, Basel
2008
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