Effects of Hydroxyeicosatetraenoic Acids on Fatty Acid Esterification in Phospholipids and Insulin Secretion in Pancreatic Islets*

Publisher Website
Google Scholar
Abstract
The ability of lipoxygenase products to become incorporated into [rat] 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 of 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. Unlabeled 5-HETE (40 nM to 8 .mu.M) 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 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. 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.