Abstract
Previous studies suggested that products of a 12-lipoxygenase pathway in the pancreatic islet may promote insulin release. To determine whether glucose augments the production of such metabolites, intact rat islets prelabeled with [3H]arachidonate were stimulated with glucose, and 12-hydroxy-5,8,10,14-icosatetraenoic acid (12-HETE) release was measured by using HPLC. D-Glucose (16.7 mM) augmented the enzymatic synthesis of 12-HETE by 271% above that seen with 0-1.7 mM glucose. The glucose effect was stereospecific and preferential for the alpha anomer; it was modestly potentiated by the cyclo-oxygenase inhibitor ibuprofen. Glucose-stimulated 12-HETE accumulation was abrogated by mannoheptulose and was reproduced by the trioses glyceraldehyde or dihydroxyacetone, suggesting that the metabolism of glucose to glucose 6-phosphate or triose phosphates (or both) is critical. Glucose also augmented [3H]arachidonate labeling of islets, suggesting an action at the level of substrate release or re-uptake (or both). These features of islet 12-HETE synthesis accord well with other known effects of glucose on beta cell function and suggest that lipoxygenase-mediated metabolites of arachidonate may be suitable candidates to mediate or amplify glucose's effects on insulin release.