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 delta-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 paralleled 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 cytidylyltransferase, 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.
Hoffman
J M
JM
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0524.
Laychock
S G
SG
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002794:Choline / Q000031:analogs & derivatives* / Q000378:metabolism*; D003566:Cytidine Diphosphate Choline / Q000378:metabolism*; D003839:Deoxyadenosines / Q000031:analogs & derivatives / Q000494:pharmacology; D013759:Dronabinol / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008555:Melitten / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D013872:Thionucleosides / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D000098:Acetophenones; D003839:Deoxyadenosines; D010713:Phosphatidylcholines; D013872:Thionucleosides; D008555:Melitten; C013919:5'-deoxy-5'-S-isobutylthioadenosine; D003566:Cytidine Diphosphate Choline; D013759:Dronabinol; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D005947:Glucose; D002794:Choline; C006821:4-bromophenacyl bromide; D002118:Calcium