Role of phospholipase and calmodulin inhibitors on insulin, arachidonic acid and prostaglandin E2 release.
Using several experimental approaches, we have studied simultaneously the effect of glucose upon insulin, arachidonic acid and prostaglandin E2 release by rat pancreatic islets. A 16.6 mmol/l glucose concentration stimulated the release of insulin, arachidonic acid and prostaglandins. All these effects were significantly reduced either by calmodulin and phospholipase A2 inhibitors, or by the omission of calcium in the incubation medium. Phospholipase A2 inhibitors do not modify the glucose-induced net 45Ca2+ uptake by isolated islets. Our results would suggest that activation of phospholipases, particularly A2, is involved in the mechanism by which glucose stimulates insulin release. This activation increases the intracellular concentration of arachidonic acid, prostaglandins and probably phospholipid degradation products, that could act as messengers for the stimulus-secretion coupling of insulin. The calcium-calmodulin complex would take part in this effect. Conversely, the glucose-induced net calcium uptake by the islets might either be preceded by phospholipase activation or not significantly affected by the blockade of its activity.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D015232:Dinoprostone; D005260:Female; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects*; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011458:Prostaglandins E / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D002147:Calmodulin; D007328:Insulin; D011458:Prostaglandins E; D016718:Arachidonic Acid; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone