Arachidonic acid and insulin release from human islets of Langerhans

To identify the role of unmetabolised arachidonic acid (AA) produced by phospholipase A2 (PLA2) enzymes, and its 12-lipoxygenase (12-LOX) and cyclooxygenase (COX) products in the insulin secretory response of human islets of Langerhans. Material and Methods: Expression of COX-1 and COX-2 mRNAs was determined by RT-PCR. Insulin secretion from perifused human islets was measured by radioimmunoassay, in the presence of inhibitors of PLA2 (AACOCF3, PACOCF3), COX and LOX (phenidone), 12-LOX (baicalein) and COX-2 (NS-398). Results: Both COX-1 and COX-2 mRNAs were amplified by RT-PCR from unstimulated human islets. Insulin release from human islets increased significantly (P<0.01) in response to 20mM glucose, with a maximal response of 825±91% basal (2mM glucose) secretion, followed by a sustained plateau of 361±38% basal (n=10). Neither the profile nor the magnitude of the glucose-induced insulin secretory response was significantly affected by 100µM of AACOCF3 or PACOCF3. Exposure of human islets to AA (50µM) transiently stimulated basal insulin secretion (peak 298±63% basal, P