title: Effects of hydroxyeicosatetraenoic acids on fatty acid esterification in phospholipids and insulin secretion in pancreatic islets.
abstract: The ability of lipoxygenase products to become incorporated into islet cell phospholipids and to affect fatty acid mobilization was investigated. Isolated intact islets or homogenized islets were incubated with tritiated 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE, 15-HETE, the leukotrienes C4 and D4, or prostaglandin E2. Tritiated 5-HETE and 12-HETE were largely esterified into phosphatidylcholine (PC) and phosphatidylethanolamine (PE) of intact islet membranes. Glucose stimulation increased [3H]5-HETE esterification to islet PC and PE. In islet homogenates, tritiated 5-HETE, 12-HETE, 15-HETE and arachidonic acid (AA) were also esterified into endogenous PC and PE, with less incorporation in phosphatidylinositol (PI) or phosphatidylserine. Addition of exogenous lysophospholipid acceptors potentiated the esterification of [3H]5-HETE to PC especially; [3H]AA was uniformly esterified to exogenous lysophospholipids. In addition, unlabeled 5-HETE (40 nM to 8 microM) affected the incorporation of [3H]AA into PC and PE of homogenates in a biphasic manner, whereas unlabeled AA inhibited [3H]AA incorporation into phospholipids in a concentration-dependent manner. Glucose (8.5 mM) stimulated the loss of labeled AA from prelabeled islet PC and PI. On the other hand, 5-HETE (40 nM) increased AA recovery in PC, PI, and PE of prelabeled islets, and HETE antagonized the glucose-stimulated release of AA from PC and PE. A 100-fold higher concentration of 5-HETE increased the glucose-stimulated loss of AA from phospholipids in prelabeled islets. Nanomolar concentrations of 5-HETE elicited a rapid and transient increase in insulin release, which was additive to the release response to a submaximal stimulatory concentration of glucose, whereas micromolar 5-HETE did not affect insulin release. Thus, pancreatic islets not only esterify HETE into phospholipids, but HETE also alters the turnover of AA in membrane phospholipids. HETE-induced changes in islet membrane fatty acid composition and/or AA mobilization may modulate stimulus-secretion coupling.
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D001091:Arachidonate Lipoxygenases; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D005227:Fatty Acids; D006893:Hydroxyeicosatetraenoic Acids; D007328:Insulin; D010743:Phospholipids; D013189:SRS-A; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D004533:Egtazic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase; D005947:Glucose; D002118:Calcium