Type IB secretory phospholipase A2 is contained in insulin secretory granules of pancreatic islet β-cells and is co-secreted with insulin from glucose-stimulated islets

Stimulation of pancreatic islets with D-glucose induces insulin secretion from secretory granules contained within the islet beta-cells. Accumulating evidence suggests that secretory phospholipases A(2) (sPLA(2)) may play a role in the distal events of secretory processes in many different cell types. Since intact pancreatic islets have been reported to contain sPLA(2), it was of interest to determine the cellular and subcellular localization of the sPLA(2) enzymes in pancreatic islets, Our findings indicate that rat pancreatic islets express mRNA for both types IB and IIA sPLA(2) enzymes and mRNA for an sPLA(2) membrane receptor. Immunoblotting analyses with antibodies directed against type IB sPLA(2) or against type IIA sPLA(2) indicate that the type IB isoform is much more abundant than the type TIA isoform in islets. Studies with purified populations of islet beta-cells prepared from dispersed islet cells by fluorescence-activated cell sorting indicate that both sPLA(2) activity and type IB sPLA(2) immunoreactive protein are substantially more abundant in beta-cells than in non-beta-cells, Subcellular fractionation studies indicate that sPLA(2) activity and type IB sPLA(2) immunoreactive protein are contained in insulin secretory granules. Stimulation of intact islets with insulin secretagogues results in the co-secretion of insulin and of sPLA(2) activity and type IB sPLA(2) immunoreactive protein into the incubation medium. These findings raise the possibility that type IB sPLA(2) participates in the secretory process of pancreatic islet beta-cells. (C) 1998 Elsevier Science B.V.