Inhibition of Arachidonate Release by Secretagogue-Stimulated Pancreatic Islets Suppresses both Insulin Secretion and the Rise in β-Cell Cytosolic Calcium Ion Concentration

Academic Article

Abstract

  • Fuel secretagogues induce hydrolysis of esterified arachidonic acid from pancreatic islet cell phospholipids and accumulation of nonesterified arachidonate at concentrations up to 35 μM. Exogenous arachidonate (5-30 μM) amplifies depolarization-induced insulin secretion from islets. Fuel secretagogueinduced hydrolysis of arachidonate from islet phospholipids occurs in Ca2+-free medium, suggesting the possible involvement of a Ca2+-independent phospholipase. In the companion paper [Gross et al. (1993) Biochemistry (preceding paper in this issue)], we demonstrated that the major islet phospholipase A2 is Ca2+-independent, ATP-stimulated, and inhibited by the haloenol lactone suicide substrate (HELSS) (E)- 6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one. Here we demonstrate that HELSS suppressed both release of the arachidonate metabolite prostaglandin E2 and insulin secretion from islets stimulated with d-glucose and the muscarinic agonist carbachol. Both prostaglandin E2 release and insulin secretion were suppressed with similar concentration profiles and time courses. Islet oxidation of [14C]- glucose to [14C]CO2, activities of islet lactate dehydrogenase and alanine and aspartate aminotransferases, and carbachol-induced inositol phosphate accumulation in islets were all unaffected by HELSS. Depolarization of isolated β-cells with 40mM KCl induced a rise in cytosolic [Ca2+] that was also unaffected by HELSS. In contrast, the 17 mM d-glucose-induced rise in β-cell [Ca2+] was inhibited by HELSS in a concentration-dependent manner, but that induced by exogenous arachidonate (15 μM) was not. These results suggest that fuel secretagogues activate the islet Ca2+-independent phospholipase A2, resulting in release of nonesterified arachidonate, which facilitates Ca2+ entry into β-cells and promotes insulin secretion. © 1993, American Chemical Society. All rights reserved.
  • Published In

  • Biochemistry  Journal
  • Digital Object Identifier (doi)

    Author List

  • Ramanadham S; Gross RW; Han X; Turk J
  • Start Page

  • 337
  • End Page

  • 346
  • Volume

  • 32
  • Issue

  • 1