Regulation of pancreatic β-cell function and mass dynamics by prostaglandin signaling

Prostaglandins (PGs) are signaling lipids derived from arachidonic acid (AA), which is metabolized by cyclooxygenase (COX)-1 or 2 and class-specific synthases to generate PGD(2), PGE(2), PGF(2 alpha), PGI(2) (prostacyclin), and thromboxane A(2). PGs signal through G-protein coupled receptors (GPCRs) and are important modulators of an array of physiological functions, including systemic inflammation and insulin secretion from pancreatic islets. The role of PGs in beta-cell function has been an active area of interest, beginning in the 1970s. Early studies demonstrated that PGE(2) inhibits glucose-stimulated insulin secretion (GSIS), although more recent studies have questioned this inhibitory action of PGE(2). The PGE(2) receptor EP3 and one of the G-proteins that couples to EP3, G alpha(Z), have been identified as negative regulators of beta-cell proliferation and survival. Conversely, PGI2 and its receptor, IP, play a positive role in the beta-cell by enhancing GSIS and preserving beta-cell mass in response to the beta-cell toxin streptozotocin (STZ). In comparison to PGE(2) and PGI(2), little is known about the function of the remaining PGs within islets. In this review, we discuss the roles of PGs, particularly PGE(2) and PGI(2), PG receptors, and downstream signaling events that alter beta-cell function and regulation of beta-cell mass.