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Objective: To assess the role of calcium-independent phospholipase A2 (iPLA2) in human pancreatic islets., Methods: The immunohistochemical analysis and Western blot were employed to examine iPLA2 expression in human pancreatic islets. Bromoenol lactone (BEL), a selective inhibitor of iPLA2, was used in a randomized controlled trial to compare its influence to glucose-stimulated insulin secretion., Results: iPLA2 was expressed predominantly in islet cells co-stained by insulin but was barely detected in the exocrine acinar cells. Western blot results indicated that islet cells expressed an iPLA2-immunoreactive band at the 80 kDa region. Glucose-stimulated insulin secretory response was dramatically reduced in islets pretreated with BEL (0.8285 +/- 0.0803 ng x islet(-1) x h(-1)) as compared with the control (1.2264 +/- 0.0568 ng x islet(-1) x h(-1)) (P < 0.01). BEL inhibited glucose stimulated insulin secretion from isolated human islets., Conclusion: iPLA2 signaling plays an important role in glucose-stimulated insulin secretion under the physiological conditions.