Pancreatic islets stimulated with d-glucosc are known to liberate arachidonie acid from membrane phospholipids and release prostaglandin E2 (PGE2). A component of the eicosanoid release induced by d-glucose has been demonstrated to occur without calcium influx and must be triggered by other coupling mechanisms. In this study, we have attempted to identify mechanisms other than calcium influx which might couple d-glucose stimulation to hydrolysis of arachidonatc from membrane phospholipids in islet cells. We have found that occupancy of the β cell plasma membrane d-glucose transporter is insufficient and that d-glucose metabolism is required to induce islet PGE2 release because 3-O-methylglucose fails to induce and mannoheptulose prevents PGE2 release otherwise induced by 17 mM d-glucose. The carbohydrate insulin secretagogues mannose and d-glyceraldehyde have also been found to induce islet PGE2, release, but the non-secretagogue carbohydrates 1-glucose and lactate do not. Carbohydrate secretagogues are known to be metabolized to yield ATP and induce depolarization of the β cell plasma membrane. We have found that depolarization by 40 mM KCl induces PGE2 release only in the presence and not in the absence of extracellular calcium, but exogenous ATP induces islet PGE2 release with or without extracellular calcium. Carbachol is demonstrated here to interact synergistically with increasing concentrations of glucose to amplify PGE2 release and insulin secretion. Pertussis toxin treatment is shown here not to prevent PGE2 release induced by glucose or carbachol bul to increase the basal rate of PGE2 release and the islet cyclic AMP content. Theophylline (10 mM) exerts similar effects. Eicosanoid release in pancreatic islets can thus be activated by multiple pathways including muscarinic receptor occupancy, calcium influx. increasing cAMP content, and a metabolic signal derived from nutrient secretagogues, such as ATP.
|Number of pages||12|
|Journal||Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism|
|State||Published - May 8 1992|
- Arachidonic acid metabolism
- Pancreas islet