Choline turnover in phosphatidylcholine of pancreatic islets. Implications for CDP-choline pathway

The CDP-choline pathway is the major route of phosphatidylcholine (PC) biosynthesis in mammalian cells. The incorporation of [¹⁴C]choline into PC of isolated pancreatic islets of the rat was time dependent, glucose stimulable, and inhibited by mannoheptulose. Removal of extracellular Ca²⁺ enhanced glucose-stimulated choline incorporation without affecting basal levels. Glucose stimulated PC synthesis in islets labeled to equilibrium with ³²PO₄ in the presence or absence of extracellular Ca²⁺. The water-soluble intermediates of the CDP-choline pathway, phosphorylcholine and CDP-choline, accumulated to a lesser extent under Ca²⁺-free conditions; however, glucose enhanced the levels of these intermediates in the presence and absence of Ca²⁺. Thus, glucose stimulates CDP-choline-pathway activity. Ca²⁺-free conditions may promote flux of choline intermediates through the pathway and retard the hydrolysis of PC. The phospholipase A₂-activating agents Δ-9-tetrahydrocannabinol and melittin enhanced [³H]choline incorporation into PC and potentiated incorporation in response to a submaximal secretagogic concentration of glucose (8.5 mM); insulin release paralled the changes in PC. p-Bromophenacyl bromide and mepacrine reduced islet glucose utilization and glucose-stimulated [³H]choline levels in PC. An inhibitor of CTP: phosphorylcholine cytidylyltranferase, 5'-deoxy-5'-isobutylthioadenosine, reduced glucose-stimulated [¹⁴C]choline incorporation into PC; insulin release was inhibited in a parallel fashion. Thus, islet PC turnover and CDP-choline pathway activity appear to be modulated by glucose metabolism and membrane phospholipid hydrolysis. PC turnover and insulin release appear to be related.