Arachidonic acid metabolism in isolated pancreatic islets. III. Effects of exogenous lipoxygenase products and inhibitors on insulin secretion

John Turk, Jerry R. Colca, Michael L. McDaniel

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Isolated pancreatic islets from the rat have been demonstrated by stable isotope dilution-mass spectrometric methods to synthesize the 12-lipoxygenase product 12-hydroxyeicosatetraenoic acid (12-HETE) in amounts of 1.7 to 2.8 ng per 103 islets. No detectable amounts of 5-HETE and only trace amounts of 15-HETE could be demonstrated by these methods. Nordihydroguaiaretic acid (NDGA) and BW755C have been demonstrated to inhibit islet 12-HETE synthesis and also to inhibit glucose-induced insulin secretion. Inhibition of insulin secretion and of 12-HETE synthesis exhibited similar dependence on the concentration of these compounds. Eicosa-5,8,11,14-tetrynoic acid (ETYA) also inhibited glucose-induced insulin secretion, as previously reported, at concentrations which inhibit islet 12-HETE synthesis. Exogenous 12-HETE partially reversed the suppression of glucose-induced insulin secretion by lipoxygenase inhibitors, but exogenous 12-hydroperoxyeicosatetraenoic acid (12-HPETE), 15-HPETE, 5-HPETE, 15-HETE, or 5-HETE did not reverse this suppression. These observations argue against the recently suggested hypothesis that islet synthesis of 5-HETE modulates insulin secretion. Suppression of glucose-induced insulin secretion by ETYA, BW755C and NDGA may be due to inhibition of the islet 12-lipoxygenase by these compounds. The possibility that other processes involved in glucose-induced insulin secretion are inhibited by ETYA, BW755C and NDGA cannot yet be excluded.

Original languageEnglish
Pages (from-to)23-36
Number of pages14
JournalBiochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
Volume834
Issue number1
DOIs
StatePublished - Mar 27 1985

Keywords

  • (Rat pancreatic islet)
  • Arachidonate metabolism
  • Hydroxyeicosanoic acid
  • Insulin secretion
  • Lipoxygenase

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