Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
Diabetes 1988 Nov
PMID:Choline turnover in phosphatidylcholine of pancreatic islets. Implications for CDP-choline pathway. 284 91

Fatty acid incorporation into specific phospholipids of isolated islets of the rat was investigated using unsaturated [14C]arachidonic acid. Glucose (25 mM) stimulated the incorporation of arachidonic acid into phosphatidylinositol (PI) and phosphatidylcholine (PC) in a time-related manner correlated with two phases of insulin release. Arachidonate incorporation was inhibited by calcium deprivation. The sulfonylurea tolbutamide stimulated an early monophasic release of insulin that was accompanied by increased [14C]arachidonate incorporation into PI and PC. The cholinergic agonist and insulin secretagogue, carbamylcholine, also promoted the incorporation of [14C]arachidonate into PI/phosphatidylserine (PS) and PC fractions. 2-Deoxy-D-glucose, which does not support insulin release, did not enhance arachidonate incorporation into phospholipids. However, phenylephrine, an inhibitor of glucose-induced insulin secretion, stimulated arachidonate turnover in PI. p-Bromophenacyl bromide, an inhibitor of phospholipase A2, markedly depressed both glucose-stimulated arachidonate incorporation into phospholipids and insulin release. The stimulated release of arachidonate from endogenous radiolabeled phospholipids provided additional evidence that phospholipase A2 mediates glucose stimulation. However, since glucose also promoted the incorporation of saturated [14C]palmitic acid into PE (phosphatidylethanolamine) and PI/PS fractions, a phospholipase A1 may also mediate the glucose response. Thus, fatty acid incorporation into islet phospholipids mediates the effects of various secretagogues on insulin release. However, the ability of phenylephrine to stimulate arachidonyl PI turnover suggests that fatty acid turnover is not a sufficient stimulus for release. Augmented levels of unsaturated fatty acids in islet cell membranes may promote fusion or activate enzymes important for hormone release.
Diabetes 1983 Jan
PMID:Fatty acid incorporation into phospholipids of isolated pancreatic islets of the rat. Relationship to insulin release. 633 3

Enhancement of arachidonic acid metabolism results in increased insulin secretion. To determine which pathways of arachidonic acid metabolism were involved in this stimulation, we studied the effects of various inhibitors of arachidonate metabolism on arginine-induced insulin and glucagon secretion in the isolated, perfused rat pancreas. The release of PGE2 from the pancreas was monitored to document the efficacy of the inhibitory drugs. p-Bromophenacyl bromide, a phospholipase A2 inhibitor, diminished PGE2 release and significantly inhibited both the early and late phases of insulin and glucagon release in response to arginine. Flurbiprofen, a specific cyclooxygenase inhibitor, decreased the early phase of insulin release and inhibited both phases of arginine-stimulated glucagon secretion; these decreases were concurrent with a large inhibition of PGE2 release. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, at a dose of 10(-5) M did not affect PGE2 release, inhibited the early phase of insulin release, and did not modify glucagon secretion. The combination of flurbiprofen and nordihydroguaiaretic acid, although the most potent in inhibiting PGE2, lowered only the early phase of insulin and had no effect on glucagon secretion. We conclude that: (1) endogenous cyclooxygenase-derived metabolites of arachidonic acid promote insulin and glucagon release, (2) endogenous lipoxygenase products preferentially stimulate insulin release, and (3) phospholipase A2 activity has an intrinsic modulatory effect on insulin and glucagon secretion.
Diabetes 1984 Oct
PMID:Possible role of endogenous arachidonic acid metabolites in stimulated release of insulin and glucagon from the isolated, perfused rat pancreas. 643 60