Arachidonic acid and insulin release from human islets of Langerhans

Belin, V. D., Squires, Paul E., Jones, P. M. and Persaud, S. J. (2001) Arachidonic acid and insulin release from human islets of Langerhans. In: 192nd Meeting of the Society for Endocrinology, 3-4 December 2001, London, UK.

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To identify the role of unmetabolised arachidonic acid (AA) produced by phospholipase A2 (PLA2) enzymes, and its 12-lipoxygenase (12-LOX) and cyclooxygenase (COX) products in the insulin secretory response of human islets of Langerhans. Material and Methods: Expression of COX-1 and COX-2 mRNAs was determined by RT-PCR. Insulin secretion from perifused human islets was measured by radioimmunoassay, in the presence of inhibitors of PLA2 (AACOCF3, PACOCF3), COX and LOX (phenidone), 12-LOX (baicalein) and COX-2 (NS-398). Results: Both COX-1 and COX-2 mRNAs were amplified by RT-PCR from unstimulated human islets. Insulin release from human islets increased significantly (P<0.01) in response to 20mM glucose, with a maximal response of 825±91% basal (2mM glucose) secretion, followed by a sustained plateau of 361±38% basal (n=10). Neither the profile nor the magnitude of the glucose-induced insulin secretory response was significantly affected by 100µM of AACOCF3 or PACOCF3. Exposure of human islets to AA (50µM) transiently stimulated basal insulin secretion (peak 298±63% basal, P<0.05, n=6) and returned to basal levels within 20 minutes, but subsequent exposure to AA in the presence of phenidone led to a further, significant increase in insulin secretion. A similar profile was obtained when human islets were exposed to NS-398. Exposure of human islets to NS-398 or baicalein in the absence of AA transiently increased basal insulin secretion (246±26% basal; 247±18% basal respectively, n=3). Conclusion: COX-2 is constitutively expressed in human islets and we have shown, for the first time, that human islets also express COX-1 mRNA. Secretion data provide compelling evidence for a stimulatory role for unmetabolised AA in the stimulation of insulin secretion from human islets of Langerhans, but they also indicate that AA generation is not obligatory for nutrient-induced insulin secretion.

Work was funded by Eli Lilly International Foundation

Additional Information:Endocrine Abstracts (2001) 2 OC7
Keywords:Arachidonic acid, insulin release, Islets of Langerhans
Subjects:C Biological Sciences > C741 Medical Biochemistry
Divisions:College of Science > School of Life Sciences
ID Code:14754
Deposited On:22 Aug 2014 10:08

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