PURPOSE: The role of icosanoids, which are products formed from the metabolism of arachidonic acid, in pancreatic islet-cell function was investigated. PROCEDURES: Secretion and biosynthesis of insulin and glucagon, biosynthesis of icosanoids, and biosynthesis of enzymes and proteins necessary for icosanoid synthesis were studied in vitro, using perfused rat pancreas, isolated and incubated islets, and insulin-secreting islet-cell lines. FINDINGS: Certain exogenous prostaglandins stimulated the secretion of insulin and glucagon; leukotrienes stimulated insulin but not glucagon release. Leukotrienes inhibited glucose-induced insulin release, but promoted insulin biosynthesis. Islet cells produced prostaglandins. Although the production of leukotrienes in islet cells could not be demonstrated conclusively, glucose-responsive biosynthesis of 5-lipoxygenase and 5-lipoxygenase-activating protein was considered evidence for leukotriene synthesis. Inhibitors of prostaglandin or leukotriene biosynthesis attenuated hormone secretion. CONCLUSION: Icosanoids produced in islet cells are involved in signal-transduction, in the form of a fine-tuning amplification of biosynthesis or secretion of insulin and glucagon in response to nutrient stimuli.

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