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- Title
The Role of Arachidonic Acid and Its Metabolites in Insulin Secretion From Human Islets of Langerhans.
- Authors
Persaud, Shanta J.; Muller, Dany; Belin, Véronique D.; Kitsou-Mylona, Isidora; Asare-Anane, Henry; Papadimitriou, Alexandros; Burns, Chris J.; Huang, Guo Cai; Amiel, Stephanie A.; Jones, Peter M.
- 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[sub 2] (cPLA[sub 2]), COX-l, 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[sub 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 µmol/1 arachidonic acid. Inhibition of COX-1 with 100 µmol/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 β-cells, so selective inhibitors of these enzymes would be expected to have a dual protective role in diabetes: they would minimize β-cell dysfunction while maintaining insulin secretion through enhancing endogenous arachidonic acid levels. Diabetes 56:197-203, 2007
- Subjects
ARACHIDONIC acid; METABOLITES; ISLANDS of Langerhans; INSULIN; CYCLOOXYGENASES; LIPOXYGENASES
- Publication
Diabetes, 2007, Vol 56, Issue 1, p197
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db06-0490