Inhibition of phospholipase A2 and insulin secretion in pancreatic islets.
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.
Konrad
R J
RJ
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6082.
Jolly
Y C
YC
Major
C
C
Wolf
B A
BA
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*
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