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

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-³²³P]ATP, OAG (100 µM) stimulated the net production of labeled phosphatidate and inhibited that of labeled phosphatidylinositol 4-phosphate. In intact islets exposed to 5.6 mM D-glucose, OAG (100 µM) decreased the outflow of ⁵⁶Rb, 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 variances 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. [ABSTRACT FROM AUTHOR]