Accumulating evidence suggests that the cytosolic
calcium-independent
phospholipase A(2) (
iPLA(2)beta) manifests a signaling role in
insulin-secreting (INS-1) beta-cells. Earlier, we reported that
insulin-secretory responses to cAMP-elevating agents are amplified in iPLA(2)beta-overexpressing INS-1 cells (Ma Z, Ramanadham S, Bohrer A, Wohltmann M, Zhang S, and Turk J. J Biol Chem 276: 13198-13208, 2001). Here, immunofluorescence, immunoaffinity, and enzymatic activity analyses are used to examine distribution of
iPLA(2)beta in stimulated INS-1 cells in greater detail. Overexpression of
iPLA(2)beta in INS-1 cells leads to increased accumulation of
iPLA(2)beta in the nuclear fraction. Increasing
glucose concentrations alone results in modest increases in insulin secretion, relative to parental cells, and in nuclear accumulation of the
iPLA(2)beta
protein. In contrast, cAMP-elevating agents induce robust increases in insulin secretion and in time-dependent nuclear accumulation of
iPLA(2)beta fluorescence, which is reflected by increases in nuclear
iPLA(2)beta
protein content and specific enzymatic activity. The stimulated effects are significantly attenuated in the presence of cell-permeable inhibitors of
protein phosphorylation and glycosylation. These findings suggest that conditions that amplify insulin secretion promote translocation of beta-cell
iPLA(2)beta to the nuclei, where it may serve a crucial signaling role.