Eicosanoids as Pluripotential Modulators of Pancreatic Islet Function

Eicosanoids both negatively and positively modulate glucose-induced insulin secretion. Although the identity of the positive modulator is uncertain, the negative modulator appears to be prostaglandin E₂ (PGE₂), because 1) glucose stimulates PGE₂ synthesis from islet cells; 2) exogenous PGE₂ inhibits glucose-induced insulin secretion; 3) inhibition of β-cell PGE₂ synthesis increases glucose-induced insulin secretion, and this increase is reversed by exogenous PGE₂; and 4) PGE₂ binds to specific β-cell receptors that are coupled to inhibitory regulatory components of adenylate cyclase whose activation decreases cAMP levels. Other possible regulatory effects of eicosanoids on islet function include modulation of islet blood flow and its immune responsiveness. From these considerations, the perspective is offered that eicosanoids are pluripotential modulators of islet function.