ROLE OF ICOSANOIDS IN BIOSYNTHESIS AND SECRETION OF INSULIN

Purpose : The role of icosanoids. which are products formed from the m etabolism of arachidonic acid, in pancreatic islet-cell function was i nvestigated. Procedures: Secretion and biosynthesis of insulin and glu cagon, bioSynthesis of icosanoids, and biosynthesis of enzymes and pro teins necessary for icosanoid synthesis were studied in vitro, using p erfused rat pancreas, isolated and incubated islets, and insulin-secre ting islet-cell lines. Findings: Certain exogenous prostaglandins stim ulated the secretion of insulin and glucagon; leukotrienes stimulated insulin but not glucagon release. Leukotrienes inhibited glucose-induc ed insulin release, but promoted insulin biosynthesis. Islet cells pro duced prostaglandins. Although the production of leukotrienes in islet cells could not be demonstrated conclusively, glucose-responsive bios ynthesis of 5-lipoxygenase and 5-lipoxygenase-activating protein was c onsidered evidence for leukotriene synthesis. Inhibitors of prostaglan din or leukotriene biosynthesis attenuated hormone secretion. Conclusi on: Icosanoids produced in islet cells are involved in signal-transduc tion, in the form of a fine-tuning amplification of biosynthesis or se cretion of insulin and glucagon in response to nutrient stimuli.