omega-Conotoxin inhibits glucose- and arachidonic acid-induced rises in intracellular [Ca2+] in rat pancreatic islet beta-cells.

Academic Article

Abstract

  • Earlier studies suggest that the accumulation of non-esterified arachidonic acid (AA) in islets following stimulation with glucose participates in the glucose-induced secretion of insulin. A possible role for AA might include the facilitation of Ca2+ influx into islet beta-cells. Recently, we demonstrated that AA induces Ca2+ influx into purified rat pancreatic islet beta-cells, prepared by fluorescence-activated cell sorting (FACS). This effect was abolished in the presence of the Ca(2+)-chelator EGTA, but was only partially reduced by the dihydropyridine (DHP) L-type Ca(2+)-channel blocker, nifedipine. This raised the possibility that DHP-insensitive Ca2+ entry mechanisms may exist in pancreatic beta-cells, in addition to the known DHP-sensitive L-type Ca2+ channels. Here we report that omega-conotoxin (CTX), which blocks omega-type Ca(2+)-channels, inhibits AA-induced Ca2+ influx by a magnitude similar to that of nifedipine and that the combination of omega-CTX and nifedipine results in a nearly additive decrement in AA-induced increases in beta-cell cytosolic [Ca2+]. We further demonstrate that bovine serum albumin, which complexes free AA and prevents AA-induced increases in cytosolic [Ca2+], also inhibits the glucose-induced increase in beta-cell [Ca2+]. These results suggest that rat pancreatic FACS-purified islet beta-cells express omega-type (DHP-insensitive) Ca(2+)-channels, in addition to DHP-sensitive Ca(2+)-channels. They further suggest that the glucose-induced accumulation of non-esterified AA in the membranes of beta-cells serves to amplify glucose-mediated Ca2+ influx into the beta-cells.
  • Published In

  • Cell Calcium  Journal
  • Keywords

  • Animals, Arachidonic Acid, Calcium, Calcium Channel Blockers, Cell Separation, Cells, Cultured, Flow Cytometry, Glucose, Islets of Langerhans, Male, Nifedipine, Peptides, Rats, Rats, Sprague-Dawley, omega-Conotoxin GVIA
  • Digital Object Identifier (doi)

    Author List

  • Ramanadham S; Turk J
  • Start Page

  • 259
  • End Page

  • 264
  • Volume

  • 15
  • Issue

  • 3