Secretagogue-induced diacylglycerol accumulation in isolated pancreatic islets. Mass spectrometric characterization of the fatty acyl content indicates multiple mechanisms of generation.
Diacylglycerol accumulation has been examined in secretagogue-stimulated pancreatic islets with a newly developed negative ion chemical ionization mass spectrometric method. The muscarinic agonist carbachol induces islet accumulation of diacylglycerol rich in arachidonate and stearate, and a parallel accumulation of 3H-labeled diacylglycerol occurs in carbachol-stimulated islets that had been prelabeled with [3H]glycerol. Islets so labeled do not accumulate 3H-labeled diacylglycerol in response to D-glucose, but D-glucose does induce islet accumulation of diacylglycerol by mass. This material is rich in palmitate and oleate and contains much smaller amounts of arachidonate. Neither secretagogue influences triacylglycerol labeling, and neither induces release of [3H]choline or [3H]phosphocholine from islets prelabeled with [3H]choline. These observations indicate that the diacylglycerol that accumulates in islets in response to carbachol arises from hydrolysis of glycerolipids, probably including phosphoinositides. The bulk of the diacylglycerol which accumulates in response to glucose does not arise from glycerolipid hydrolysis and must therefore reflect de novo synthesis. The endogenous diacylglycerol which accumulates in secretagogue-stimulated islets may participate in insulin secretion because exogenous diacylglycerol induces insulin secretion from islets, and an inhibitor of diacylglycerol metabolism to phosphatidic acid augments glucose-induced insulin secretion.
Wolf
B A
BA
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Easom
R A
RA
Hughes
J H
JH
McDaniel
M L
ML
Turk
J
J
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D004075:Diglycerides / Q000378:metabolism*; D005989:Glycerides / Q000378:metabolism*; D006868:Hydrolysis; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D011919:Rats, Inbred Strains; D013229:Stearic Acids / Q000378:metabolism
D001095:Arachidonic Acids; D004075:Diglycerides; D005989:Glycerides; D007328:Insulin; D013229:Stearic Acids; D016718:Arachidonic Acid; C031183:stearic acid; D002217:Carbachol