Leukotrienes stimulate insulin release from the rat pancreas.

We and others had observed that drugs that inhibit the lipoxygenase enzymes inhibit insulin release. The aim of the study was to search for evidence that, among the products of lipoxygenase-activated metabolism of arachidonic acid, leukotrienes (LTs) promote insulin release. Synthetic LTB4, LTC4, LTD4, and LTE4 were administered over 1-min periods to the isolated, perfused rat pancreas in the presence of 5.6 mM glucose. Perfusion effluent levels of insulin and glucagon were measured by radioimmunoassay. LTB4 and LTC4 and, to a lesser extent, LTE4 and LTD4 stimulated insulin release in a dose-related manner, in the concentration range of 10(-11) to 10(-7) M. Only 10(-7) M LTC4 stimulated glucagon release. We conclude that (i) among the arachidonic acid metabolites, LTs are involved in the modulation of secretion of pancreatic islet hormones and (ii) LTs preferentially promote insulin release.