Effects of inhibitors of eicosanoid synthesis on insulin release by neonatal pancreatic islets.

In the pancreatic islet, eicosanoids may arise from both cyclooxygenase- and lipoxygenase-dependent metabolism of arachidonic acid. The inclusion of inhibitors of selective steps in these pathways indicated that in cultured neonatal rat islets, arachidonic acid may be metabolised through both pathways, concurrent with insulin release stimulated by D-glucose, D-glyceraldehyde and 2-ketoisocaproate. The effects of the inhibitors suggested that the products of the lipoxygenase pathway were necessary for the stimulatory effects of nutrients to be observed. In contrast to glucose, where insulin release was stimulated in the presence of inhibitors of cyclooxygenase, the stimulatory action of D-glyceraldehyde, 2-ketoisocaproate and melittin was only minimally affected by these inhibitors, although it was inhibited by lipoxygenase inhibition. These findings support a major stimulatory role for products of the lipoxygenase pathway of arachidonic acid metabolism in nutrient-induced secretion, and a negative or modulatory role of cyclooxygenase pathway products on glucose-stimulated insulin release in the neonatal islet.