Stimulation of protein kinase C and insulin release by 1-oleoyl-2-acetyl-glycerol

Abstract

The membrane‐accessible diacylglycerol 1‐oleoyl‐2‐acetyl‐sn‐glycerol (OAG, 5–500 μM) caused a dose‐related activation of protein kinase C in rat islet homogenates. In islet cell membranes exposed to [γ‐³²P]ATP, OAG (100 μM) stimulated the net production of labelled phosphatidate and inhibited that of labelled phosphatidylinositol 4‐phosphate. In intact islets exposed to 5.6 mM D‐glucose, OAG (100 μM) decreased the outflow of ⁸⁶Rb, increased that of ⁴⁵Ca and caused a rapid stimulation of insulin release. The secretory response to OAG was dose‐related in the 50–500 μM range, being most marked, in relative terms, at a glucose concentration close to the threshold value for stimulation of insulin release by this hexose. It was decreased but not abolished in the absence of CaCl₂ and presence of EGTA. At variance with tumor‐promoting phorbol esters, OAG failed to potentiate insulin release stimulated by a hypoglycaemic sulphonylurea. Although these findings support the view that activation of protein kinase C by diacylglycerol represents an efficient modality for stimulation of insulin release, they suggest that the effect of OAG upon islet function may not be solely attributable to such an activation.