Carbamylcholine and ouabain effects on Ca²⁺ handling and insulin release in islets from rats depleted in long-chain polyunsaturated ω3 fatty acids

Abstract

A number of metabolic, ionic and secretory variables were recently found to be affected in pancreatic islets obtained from second generation rats depleted in long-chain polyunsaturated ω3 fatty acids (ω3 rats). The present study further documents three sets of anomalies in such islets. First, after 90 min exposure to d-glucose (8.3 mM), the release of insulin from perifused islets, prelabelled with ⁴⁵Ca, is lower in ω3 rats than in control animals, despite comparable ⁴⁵Ca fractional outflow rate. Second, over 15 min exposure to carbamylcholine (0.1 mM), in the presence of d-glucose, the cytosolic concentration of Ca²⁺ is increased to a greater relative extent in dispersed islet cells from ω3 rats, as compared to control animals. This coincides with a greater relative increase in insulin output from perifused islets during the second phase of the secretory response to the cholinergic agent. Last, the increase provoked by ouabain (1.0 mM) in cytosolic Ca²⁺ concentration, ⁴⁵Ca fractional outflow rate and insulin release are all delayed in the ω3 rats. Taking into account the decreased activity of Na⁺, K⁺-ATPase in the islets of ω3 rats, these findings are interpreted as reflecting an impaired priming of insulin-producing cells when first exposed for 105 min to a physiological postprandial concentration of d-glucose.