Effect of lysophospholipids, arachidonic acid and other fatty acids on regulation of Ca2+ transport in permeabilized pancreatic islets

Abstract The immediate reaction products of PLA 2 -mediated hydrolysis of phospholipids were tested for their ability to induce Ca 2+ mobilization from internal stores in permeabilized ob ob mouse pancreatic islets. Lysophospholipids and unsaturated fatty acids increased the free Ca 2+ concentration in the incubation medium of permeabilized ob ob mouse pancreatic islets. The potency of the lysophospholipids decreased in the following order: lysophosphatidylcholine = lysophosphatidylglycerol ⪢ lysophosphatidylinositol > lysophosphatidylserine ⪢ lysophosphatidylethanolamine. Arachidonic acid and palmitoleic acid had a potency comparable to lysophosphatidylinositol, while palmitic acid was ineffective. The Ca 2+ -mobilizing effect of inositol-1,4,5-trisphosphate (IP 3 ) in permeabilized islet cells was additive to the lysophospholipid effect, indicating different sites of action. Both Ca 2+ -mobilizing effects were counteracted by the polyamine spermine, while the presence of Mg 2+ shifted the Ca 2+ concentrations to higher levels. Since not only an activation of a phospholipase C but also an activation of a phospholipase A 2 with subsequent generation of lysophospholipids and free fatty acids is reported to occur in glucose-induced insulin secretion, the interaction of the phospholipase C reaction product IP 3 with a lysophospholipid or an unsaturated fatty acid may affect the extent and duration of the rise in the free cytoplasmic Ca 2+ concentration responsible for initiation of insulin secretion.