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 microM) caused a dose-related activation of protein kinase C in rat islet homogenates. In islet cell membranes exposed to [gamma-32P]ATP, OAG (100 microM) 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 microM) 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 microM 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.
Malaisse
W J
WJ
Dunlop
M E
ME
Mathias
P C
PC
Malaisse-Lagae
F
F
Sener
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D004075:Diglycerides / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005989:Glycerides / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D012413:Rubidium / Q000378:metabolism
D004075:Diglycerides; D005989:Glycerides; D007328:Insulin; D008563:Membrane Lipids; C038237:1-oleoyl-2-acetylglycerol; D011494:Protein Kinases; D011493:Protein Kinase C; D012413:Rubidium; D002118:Calcium