Glucose and carbachol synergistically stimulate phosphatidic acid accumulation in pancreatic islets.
Phosphatidic acid has been previously implicated as an intracellular mediator of insulin secretion. Very little is known, however, about endogenous phosphatidic acid levels in islets. We now show, for the first time, that glucose and carbachol, at concentrations which stimulate insulin secretion, significantly increase endogenous phosphatidic acid levels in pancreatic islets by 2-fold at 1 min, nearly 3-fold at 2 min, and over 3-fold at 30 min compared to control. Possible mechanisms include de novo synthesis from glucose and/or activation of phospholipase D. Our data, taken together with previous studies, suggest that phosphatidic acid may have a central role in insulin secretion as an intracellular mediator.
Konrad
R J
RJ
Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia 19104-6082.
Jolly
Y C
YC
Wolf
B A
BA
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D004075:Diglycerides / Q000302:isolation & purification / Q000378:metabolism; D004357:Drug Synergism; D005227:Fatty Acids / Q000302:isolation & purification / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010712:Phosphatidic Acids / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D004075:Diglycerides; D005227:Fatty Acids; D010712:Phosphatidic Acids; D002217:Carbachol; D005947:Glucose