Modulation of insulin secretion by lipoxygenase products of arachidonic acid. Relation to lipoxygenase activity of pancreatic islets.

摘要: Abstract Glucose (16.7 mM)-induced insulin secretion from isolated pancreatic islets of rats was inhibited by nordihydroguaiaretic acid (NDGA), 1-phenyl-3-pyrazolidinone (phenidone), 3-amino-1-(3-trifluoromethylphenyl)-2-pyrazoline (BW755C), 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA861), and 2,6-di-tert-butyl-4-methylphenol (BHT). Indomethacin aspirin, however, failed to inhibit the glucose-induced but rather tended enhance it. The 15-hydroxy-5,8,11,13-eicosatetraenoic (15-HETE) (50 microM), 15-hydroperoxy-5,8,11,13-eicosatetraenoic (15-HPETE) (100 12-hydroxy-5,8,10,14-eicosatetraenoic (12-HETE) not 5-hydroxy-6,8,11,14-eicosatetraenoic (5-HETE) microM). Exogenous 5-HETE (10 microM) induced significant in a low glucose (3.3 mM) medium. Racemic also showed insulinotropic effect concentration-dependent manner with concentrations 20 microM or above, whereas 12-HETE, 15-HETE, 15-HPETE, 5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid, 5-hydroxy-6-glutathionyl-7,9,11,14-eicosatetraenoic 5-hydroxy-6-cysteinylglycinyl-7,9,11,14-eicosatetraenoic prostaglandin E2, F2 alpha induce secretion. Although release observed arachidonic (greater than equal 100 reduce cell viability evident at 200 microM. When 10,000 X g supernatant islet homogenate incubated [3H]arachidonic 37 degrees C presence GSH Ca2+, labeled metabolites then extracted ethyl acetate subjected reverse phase high pressure liquid chromatography, several radioactive peaks, coeluted authentic 15-, 12-, 5-HETE, were observed. peaks completely suppressed addition either NDGA, BW755C, phenidone into results support our contention i.e. involvement lipoxygenase product(s) secretory mechanism insulin, further suggest that 5-lipoxygenase system may play role.