Carbachol stimulation of phospholipase A2 and insulin secretion in pancreatic islets.

  title={Carbachol stimulation of phospholipase A2 and insulin secretion in pancreatic islets.},
  author={Robert J. Konrad and Yannick Jolly and Christopher D Major and Bryan A. Wolf},
  journal={The Biochemical journal},
  volume={287 ( Pt 1)},
Arachidonic acid has been implicated as a second messenger in insulin secretion by islets of Langerhans. D-Glucose, the major physiological stimulus, increases unesterified arachidonate accumulation in islets. We now show, for the first time, that the muscarinic agonist carbachol, at concentrations which stimulate insulin secretion, causes a rapid and nearly 3-fold increase in arachidonic acid accumulation in islets. The combination of glucose and carbachol has an additive effect on… 
Transient activation of calcium-dependent phospholipase A2 by insulin secretagogues in isolated pancreatic islets.
It is suggested that activation of islet Ca(2+)-dependent phospholipase A2 may be important in a distal process of insulin secretion, such as secretory granule exocytosis.
Dual pathways for carbamylcholine-stimulated arachidonic acid release in rat pancreatic acini
It is demonstrated that phospholipase A2 and diacylglycerol lipase are activated and arachidonic acid is released in pancreatic acini by carbamylcholine.
Diacylglycerol hydrolysis to arachidonic acid is necessary for insulin secretion from isolated pancreatic islets: sequential actions of diacylglycerol and monoacylglycerol lipases.
It is shown that diacylglycerol, a product of phospholipase C action, is a major source of free arachidonic acid in islets and is markedly inhibits glucose- and carbachol-induced increases in islet arachIDonic acid levels, as measured by gas chromatography with electron-capture detection of its pentafluorobenzyl esters.
Fuel secretagogue stimulation of arachidonic acid accumulation in fresh and cultured pancreatic islets
It is shown that non-metabolizable analogs of glucose which do not stimulate insulin secretion fail to cause significant accumulation of unesterified arachidonic acid in pancreatic islets.
Involvement of phospholipase A2 and arachidonic acid in cholecystokinin-8-induced insulin secretion in rat islets
It is concluded that CCK-8-induced insulin secretion is partially mediated by a pathway involving PLA2, and that the formed AA, rather than its metabolites, is of importance.
Inhibition of Ca2+-independent phospholipase A2 results in insufficient insulin secretion and impaired glucose tolerance.
It is unambiguously demonstrated that iPLA2 signaling plays an important role in glucose-stimulated insulin secretion under physiological conditions and that impaired glucose tolerance was due to insufficient insulin secretion rather than decreased insulin sensitivity.
The Role of Arachidonic Acid and Its Metabolites in Insulin Secretion From Human Islets of Langerhans
Data indicate that the stimulation of insulin secretion from human islets in response to arachidonic acid does not require its metabolism through COX-2 and 5-/12-LOX pathways, and selective inhibitors of these enzymes would have a dual protective role in diabetes.
Mass spectrometric characterization of arachidonate-containing plasmalogens in human pancreatic islets and in rat islet beta-cells and subcellular membranes.
Observations are consistent with the hypotheses that islet beta-cell ASCI-PLA2-catalyzed hydrolysis of arachidonate from endogenous plasmenylethanolamine substrates may occur in membrane compartments which participate in regulation of the beta- cell cytosolic [Ca2+] and that this may be an intermediary biochemical event in the induction of insulin secretion.
Arachidonic acid mobilizes Ca2+ from the endoplasmic reticulum and an acidic store in rat pancreatic β cells.
The finding suggests that arachidonic acid mobilizes Ca(2+) from the endoplasmic reticulum as well as an acidic store and both stores could be depleted by IP(3) receptor agonist.
Phospholipid hydrolysis in pancreatic islet beta cells and the regulation of insulin secretion
Selective inhibition of this islet ATP-stimulated, Ca 2+ -independent (ASCI)-phospholipase A 2 (PLA 2 ) with a haloenol lactone suicide substrate which is sterically similar to plasmalogens suppresses the D-glucose-induced hydrolysis of arachidonate from β-cell phospholipids, the rise inβ-cell cytosolic [Ca 2+ ], and insulin secretion.