A link between endoplasmic reticulum stress‐induced β ‐cell apoptosis and the group VIA Ca 2+ ‐independent phospholipase A 2 (iPLA 2 β )

Endoplasmic reticulum (ER) stress is becoming recognized as an important contributing factor in various diseases, including diabetes mellitus. Prolonged ER stress can cause β ‐cell apoptosis; however, the underlying mechanism(s) that contribute to this process are not well understood. Early reports suggested that arachidonic acid metabolites and a Ca 2+ ‐independent phospholipase A 2 (iPLA 2 ) activity play a role in β ‐cell apoptosis. The PLA 2 family of enzymes catalyse the hydrolysis of the sn ‐2 substituent (i.e. arachidonic acid) of membrane phospholipids. In light of our findings that the pancreatic islet β ‐cells are enriched in arachidonate‐containing phospholipids and express the group VIA iPLA 2 β , we considered the possibility that iPLA 2 β participates in ER stress‐induced β ‐cell apoptosis. Our work revealed a novel mechanism, involving ceramide generation and triggering of mitochondrial abnormalities, by which iPLA 2 β participates in the β ‐cell apoptosis process. Here, we review our evidence linking ER stress, β ‐cell apoptosis and iPLA 2 β . Continued studies in this area will increase our understanding of the contribution of iPLA 2 β to the evolution of diabetes mellitus and will further our knowledge of factors that influence β ‐cell health in diabetes mellitus and identify potential targets for future therapeutic interventions to prevent β ‐cell death.