Metabolism of lysophospholipids in intact rat islets. The insulin secretagogue p-hydroxymercuribenzoic acid impairs lysophosphatidylcholine catabolism and permits its accumulation.
Although recent studies implicate lysophospholipids (lyso-PLs) in stimulus-secretion coupling in the pancreatic islet, almost no data on lyso-PL metabolism therein exist. Therefore, intact rat islets were loaded with insulinotropic and non-toxic concentrations of 1-[14C]palmitoyl-lysophosphatidylcholine (lyso-PC) via transbilayer movement, and its metabolic fate was studied. The time-dependent hydrolysis of lyso-PC to fatty acid (lysophospholipase activity), its conversion to phosphatidylcholine (putative acyltransferase activity) and, to a lesser degree, the appearance of label in phosphatidylethanolamine (putative transacylase or base exchange activity) were observed. p-Hydroxymercuribenzoic acid (PHMB) at 100 microM (a concentration previously demonstrated to elicit potent exocytotic insulin release) inhibited all three activities (by 56, 46 and 75%, respectively) and led to the intracellular accumulation of lyso-PC. Antimycin A inhibited phosphatidylcholine formation but not lysophospholipase activity; lyso-PC did not accumulate, implying that blockade of both of the major metabolic pathways is required to induce a detectable increment in lyso-PC levels. Calculations derived from data using the lowest effective insulinotropic concentration of lyso-PC suggested that increments in lyso-PC accumulation at critical membrane sites of less than 10-15% above basal values are sufficient to trigger insulin release. Since PHMB elicited increments of 50-100% in lyso-PC after its translocation into islets, support is provided for the earlier contention that lyso-PLs mediate the insulinotropic effect of PHMB. In addition, these studies may provide a more precise experimental paradigm for future studies of islet lyso-PL metabolism.
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D006902:Hydroxymercuribenzoates / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D008246:Lysophospholipids; D008297:Male; D010743:Phospholipids / Q000378:metabolism*; D010955:Plasmalogens / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D006902:Hydroxymercuribenzoates; D007328:Insulin; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D010743:Phospholipids; D010955:Plasmalogens; C020791:phosphatidal ethanolamines; C030601:4-hydroxymercuribenzoate; C006065:We 201; D000968:Antimycin A; D000255:Adenosine Triphosphate