Carbamylcholine and ouabain effects on Ca2+ handling and insulin release in islets from rats depleted in long-chain polyunsaturated omega 3 fatty acids.
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 omega 3 fatty acids (omega 3 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 omega 3 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 omega 3 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 omega 3 rats. Taking into account the decreased activity of Na+, K+-ATPase in the islets of omega 3 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.
Laboratory of Experimental Hormonology, Brussels Free University, 808 Route de Lennik, 1070, Brussels, Belgium.
Karim
K
Louchami
Ying
Y
Zhang
Yvon A
YA
Carpentier
Jean-Michel
JM
Chardigny
Willy J
WJ
Malaisse
André
A
Herchuelz
Abdullah
A
Sener
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015525:Fatty Acids, Omega-3 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D011922:Rats, Mutant Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors
D002316:Cardiotonic Agents; D015525:Fatty Acids, Omega-3; D007328:Insulin; D010042:Ouabain; D002217:Carbachol; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D002118:Calcium