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 PGD2 , PGE2 , PGF2α , PGI2 (prostacyclin), and thromboxane A2 . 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 β-cell function has been an active area of interest, beginning in the 1970s. Early studies demonstrated that PGE2 inhibits glucose-stimulated insulin secretion (GSIS), although more recent studies have questioned this inhibitory action of PGE2 . The PGE2 receptor EP3 and one of the G-proteins that couples to EP3, GαZ , have been identified as negative regulators of β-cell proliferation and survival. Conversely, PGI2 and its receptor, IP, play a positive role in the β-cell by enhancing GSIS and preserving β-cell mass in response to the β-cell toxin streptozotocin (STZ). In comparison to PGE2 and PGI2 , little is known about the function of the remaining PGs within islets. In this review, we discuss the roles of PGs, particularly PGE2 and PGI2 , PG receptors, and downstream signaling events that alter β-cell function and regulation of β-cell mass.