Glucose increases the synthesis of lipoxygenase-mediated metabolites of arachidonic acid in intact rat islets.
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.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D008084:Lipoxygenase / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; D008084:Lipoxygenase; D005978:Glutathione; D005947:Glucose