Effects of phosphatidic acid on islet cell phosphoinositide hydrolysis, Ca2+, and adenylate cyclase.
Phosphatidic acid may be raised in glucose-stimulated islet cells through hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) and de novo synthesis with glucose-derived trioses. The mechanism by which exogenous phosphatidic acid from egg yolk lecithin may augment insulin secretion was investigated in neonatal beta-cells. In whole cells labeled with [2,8-3H]-adenine, a dose-dependent increase in phosphatidic acid-stimulated adenylate cyclase activity was seen, and a small intracellular transient free-Ca2+ rise was seen in Fura 2AM-loaded cells. In [gamma-32P]ATP-labeled membranes from those beta-cells, phosphatidic acid effected PIP2 hydrolysis. These phosphatidic acid-stimulated effects were not sensitive to preincubation with Bordetella pertussis exotoxin. The findings are consistent with a stimulatory effect of exogenous phosphatidic acid on insulin release and indicate an effect at the plasma membrane. It is possible that newly synthesized phosphatidic acid may function similarly to amplify intracellular events in glucose-stimulated islet cells through both local Ca2+ concentration and cyclic AMP-sensitive mechanisms. The participation of newly synthesized phosphatidic acid derived from glucose could provide a link between the metabolism of glucose and insulin release.
Dunlop
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ME
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Larkins
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RG
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D006868:Hydrolysis; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D010712:Phosphatidic Acids / Q000096:biosynthesis / Q000494:pharmacology*; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D007328:Insulin; D010712:Phosphatidic Acids; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D000262:Adenylyl Cyclases; D005947:Glucose; D002118:Calcium