TYPE IB SECRETORY PHOSPHOLIPASE A(2) IS CONTAINED IN INSULIN SECRETORY GRANULES OF PANCREATIC-ISLET BETA-CELLS AND IS CO-SECRETED WITH INSULIN FROM GLUCOSE-STIMULATED ISLETS

Stimulation of pancreatic islets with D-glucose induces insulin secret ion from secretory granules contained within the islet beta-cells. Acc umulating 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 report ed to contain sPLA(2), it was of interest to determine the cellular an d subcellular localization of the sPLA(2) enzymes in pancreatic islets , Our findings indicate that rat pancreatic islets express mRNA for bo th types IB and IIA sPLA(2) enzymes and mRNA for an sPLA(2) membrane r eceptor. Immunoblotting analyses with antibodies directed against type IB sPLA(2) or against type IIA sPLA(2) indicate that the type IB isof orm 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 subst antially more abundant in beta-cells than in non-beta-cells, Subcellul ar fractionation studies indicate that sPLA(2) activity and type IB sP LA(2) immunoreactive protein are contained in insulin secretory granul es. 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 r aise the possibility that type IB sPLA(2) participates in the secretor y process of pancreatic islet beta-cells. (C) 1998 Elsevier Science B. V.