title: Regulation of pancreatic β-cell function and mass dynamics by prostaglandin signaling.
abstract: 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 PGE2inhibits glucose-stimulated insulin secretion (GSIS), although more recent studies have questioned this inhibitory action of PGE2. The PGE2receptor 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, PGI2and 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 PGE2and PGI2, little is known about the function of the remaining PGs within islets. In this review, we discuss the roles of PGs, particularly PGE2and PGI2, PG receptors, and downstream signaling events that alter β-cell function and regulation of β-cell mass.
authors.affiliation: Department of Veterans Affairs, Tennessee Valley Health Authority, Nashville, TN, USA.|Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.|Program in Developmental Biology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Bethany A
authors.initials: BA
authors.lastname: Carboneau
authors.affiliation: Department of Veterans Affairs, Tennessee Valley Health Authority, Nashville, TN, USA.|Department of Medicine, Division of Nephrology, Vanderbilt University Medical Center, Nashville, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Breyer
authors.affiliation: Department of Veterans Affairs, Tennessee Valley Health Authority, Nashville, TN, USA. maureen.gannon@vanderbilt.edu.|Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA. maureen.gannon@vanderbilt.edu.|Program in Developmental Biology, Vanderbilt University, Nashville, TN, USA. maureen.gannon@vanderbilt.edu.|Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA. maureen.gannon@vanderbilt.edu.|Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA. maureen.gannon@vanderbilt.edu.
authors.forename: Maureen
authors.initials: M
authors.lastname: Gannon
keywords: GSIS; Proliferation; Prostaglandins; β-cell