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The role of arachidonic acid and its metabolites in insulin secretion from human islets of langerhans

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dc.contributor.author Anane-Asare, H.
dc.contributor.author Persaud, S. J.
dc.contributor.author Muller, D.
dc.contributor.author Belin, V. D.
dc.contributor.author Kitsou-Mylona, I.
dc.contributor.author Papadimitriou, A.
dc.contributor.author Burns, C. J.
dc.contributor.author Huang, G. C.
dc.contributor.author Amiel, S. A.
dc.contributor.author Jones, P. M
dc.date.accessioned 2012-05-02T17:00:59Z
dc.date.accessioned 2017-10-19T11:50:32Z
dc.date.available 2012-05-02T17:00:59Z
dc.date.available 2017-10-19T11:50:32Z
dc.date.issued 2007
dc.identifier.uri http://197.255.68.203/handle/123456789/958
dc.description.abstract The roles played by arachidonic acid and its cyclooxygenase (COX)-generated and lipoxygenase (LOX)-generated metabolites have been studied using rodent islets and insulin-secreting cell lines, but very little is known about COX and LOX isoform expression and the effects of modulation of arachidonic acid generation and metabolism in human islets. We have used RT-PCR to identify mRNAs for cytosolic phospholipase A(2) (cPLA(2)), COX-1, COX-2, 5-LOX, and 12-LOX in isolated human islets. COX-3 and 15-LOX were not expressed by human islets. Perifusion experiments with human islets indicated that PLA(2) inhibition inhibited glucose-stimulated insulin secretion, whereas inhibitors of COX-2 and 12-LOX enzymes enhanced basal insulin secretion and also secretory responses induced by 20 mmol/l glucose or by 50 mumol/l arachidonic acid. Inhibition of COX-1 with 100 mumol/l acetaminophen did not significantly affect glucose-stimulated insulin secretion. These data indicate that the stimulation of insulin secretion from human islets in response to arachidonic acid does not require its metabolism through COX-2 and 5-/12-LOX pathways. The products of COX-2 and LOX activities have been implicated in cytokine-mediated damage of beta-cells, so selective inhibitors of these enzymes would be expected to have a dual protective role in diabetes: they would minimize beta-cell dysfunction while maintaining insulin secretion through enhancing endogenous arachidonic acid levels. en_US
dc.language.iso en en_US
dc.publisher Diabetes 56(1):197-203 en_US
dc.title The role of arachidonic acid and its metabolites in insulin secretion from human islets of langerhans en_US
dc.type Article en_US


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