Konrad R J, Jolly Y C, Major C, Wolf B A
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6082.
Biochim Biophys Acta. 1992 Jun 10;1135(2):215-20. doi: 10.1016/0167-4889(92)90139-3.
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.
花生四烯酸可能是胰岛素分泌的重要介质，因为：（1）葡萄糖激活磷脂酶A2，从而增加内源性游离花生四烯酸水平；（2）花生四烯酸从胰岛内质网中动员Ca2+；（3）有人提出花生四烯酸可调节β细胞中的电压依赖性Ca2+通道。我们使用了磷脂酶A2抑制剂（对戊基肉桂酰基）邻氨基苯甲酸（ACA）来确定葡萄糖诱导的胰岛素分泌是否需要磷脂酶A2的激活。ACA以剂量依赖的方式抑制葡萄糖诱导的胰岛素分泌，以及甘油醛和α-酮异己酸诱导的胰岛素分泌。ACA还完全消除了葡萄糖诱导的花生四烯酸积累，但不影响磷脂酶C，这表明它对磷脂酶A2具有特异性。此外，ACA不抑制葡萄糖氧化。这些观察结果表明，葡萄糖诱导的花生四烯酸增加对胰岛素分泌至关重要。
