FIGURE 7.

General scheme illustrating the arachidonic acid pathway through which IL-1β regulates PGE₂ production. Arachidonic acid is cleaved from phospholipid by phospholipase A₂ (PLA₂), followed by synthesis of endoperoxides (PGG₂, PGH₂) via COX-1 and COX-2. Activation of COX-2 by IL-1β increases intracellular PGE₂ levels. This scheme emphasizes that islets differ importantly from other cell lines and tumor tissues, because they contain little to no mPGES-1 in mice and rats, and although detectable in humans, this protein is not increased by IL-1β, whereas COX-2 is. Therefore, COX-2, and not mPGES-1, in islets is the mechanism whereby IL-1β increases PGE₂ production, which in turn inhibits glucose-induced insulin secretion.