Abstract

The β-isoform of group VIA calcium-independent phospholipase A₂ (iPLA₂β) does not require calcium for activation, is stimulated by ATP, and is sensitive to inhibition by a bromoenol lactone suicide substrate. Several potential functions have been proposed for iPLA₂β. Our studies indicate that iPLA₂β is expressed in β-cells and participates in glucose-stimulated insulin secretion but is not involved in membrane phospholipid remodeling. If iPLA₂β plays a signaling role in glucose-stimulated insulin secretion, then conditions that impair iPLA₂β functions might contribute to the diminished capacity of β-cells to secrete insulin in response to glucose, which is a prominent characteristic of type 2 diabetes. Our recent studies suggest that iPLA₂β might also participate in β-cell proliferation and apoptosis and that various phospholipid-derived mediators are involved in these processes. Detailed characterization of the iPLA₂β protein level reveals that β-cells express multiple isoforms of the enzyme, and our studies involve the hypothesis that different isoforms have different functions.