title: Inhibition of phospholipase A2 and insulin secretion in pancreatic islets.
abstract: Arachidonic acid may be an important mediator of insulin secretion since (1) glucose activates phospholipase A2 thus increasing endogenous unesterified levels of arachidonic acid, (2) arachidonic acid mobilizes Ca2+ from the islet endoplasmic reticulum and (3) arachidonic acid has been proposed to regulate voltage-dependent Ca2+ channels in the beta-cell. We have used the phospholipase A2 inhibitor, (p-amylcinnamoyl)anthranilic acid (ACA), to determine whether phospholipase A2 activation is required for glucose-induced insulin secretion. ACA inhibited in a dose-dependent manner glucose-induced insulin secretion, as well as glyceraldehyde and alpha-ketoisocaproic acid-induced insulin secretion. ACA also totally abolished glucose-induced arachidonate accumulation but did not affect phospholipase C suggesting that it was specific for phospholipase A2. Furthermore, ACA did not inhibit glucose oxidation. These observations suggest that glucose-induced arachidonate increase is essential for insulin secretion.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6082.
authors.forename: R J
authors.initials: RJ
authors.lastname: Konrad
authors.forename: Y C
authors.initials: YC
authors.lastname: Jolly
authors.forename: C
authors.initials: C
authors.lastname: Major
authors.forename: B A
authors.initials: BA
authors.lastname: Wolf
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000096:biosynthesis* / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D005985:Glyceraldehyde / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D007651:Keto Acids / Q000494:pharmacology; D008297:Male; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: D007328:Insulin; D007651:Keto Acids; D062367:ortho-Aminobenzoates; D016718:Arachidonic Acid; D005985:Glyceraldehyde; C013082:alpha-ketoisocaproic acid; D010741:Phospholipases A; D054467:Phospholipases A2; D005947:Glucose