Amplification of insulin secretion by lipid messengers

Academic Article

Abstract

  • D-glucose induces a rise in pancreatic islet β-cell cytosolic [Ca2+] by processes requiring both glucose metabolism and Ca2+ entry from the extracellular space, and this Ca2+ signal is thought to be critical to the induction of insulin secretion. Insulin secretagogues also induce phospholipid hydrolysis and accumulation of phospholipid-derived mediators in islets, including the lipid messengers DAG, nonesterified arachidonic acid, and arachidonate 12-LO products. This study offers the following viewpoints on potential roles of these lipid messengers in insulin secretion as working hypotheses: 1) the Ca2+ signal provided to the β-cell by D-glucose induces insulin secretion only in the context of amplifying background signals provided by the β-cell content of messengers including DAG; 2) muscarinic receptor agonists amplify glucose-induced insulin secretion in part by altering the β-cell content of DAG; 3) the Ca2+ signal provided by metabolism of D-glucose is amplified by the level of nonesterified arachidonic acid in β-cell membranes, which acts to facilitate Ca2+ entry; 4) metabolism of glucose induces accumulation of nonesterified arachidonate in β-cells via activation of a recently identified ASCI-PLA2 enzyme, which may be a component of the β-cell fuel sensor apparatus; and 5) arachidonate 12-LO metabolites are potential candidates as adjunctive modulators of β- cell K+-channel activity.
  • Published In

  • Diabetes  Journal
  • Digital Object Identifier (doi)

    Author List

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

  • 367
  • End Page

  • 374
  • Volume

  • 42
  • Issue

  • 3