Free fatty acid accumulation in secretagogue-stimulated pancreatic islets and effects of arachidonate on depolarization-induced insulin secretion.
Free fatty acid accumulation in secretagogue-stimulated pancreatic islets and effects of arachidonate on depolarization-induced insulin secretion.
复制标题
促分泌素刺激的胰岛中游离脂肪酸的积累以及花生四烯酸对去极化诱导的胰岛素分泌的影响。
DOI：
10.1021/bi00240a004
复制
发表时间：
1991
期刊：
影响因子：
2.9
通讯作者：
Turk,J
中科院分区：
文献类型：
--
作者：
Wolf,BA;Pasquale,SM;Turk,J
摘要：用气相色谱-质谱法对胰岛素促分泌剂刺激后的胰岛游离脂肪酸进行了定量。已发现燃料促分泌剂D-葡萄糖对胰岛棕榈酸水平的影响很小，但确实诱导了足够未酯化的花生四烯酸的质量积累，使细胞水平增加了38-75ĩ。这种游离的花生四烯酸很少被释放到灌流介质中，大多数仍然与胰岛有关。葡萄糖诱导的胰岛细胞磷脂中花生四烯酸的水解是通过胰岛中花生四烯酸代谢产物前列腺素E_2(PGE_2)的释放来反映的。去极化胰岛素促分泌剂托丁胺(被认为是通过关闭0细胞ATP敏感K+通道和通过电压依赖通道使细胞外钙离子内流起作用)和钙离子载体A23187也被发现诱导胰岛内游离阿拉伯酸蓄积和前列腺素E_2释放。令人惊讶的是，发现葡萄糖诱导的二十烷类化合物释放的主要部分不需要钙内流，即使在无钙介质中，在存在钙离子螯合剂EGTA的情况下，在存在钙离子通道阻滞剂维拉帕米和硝苯地平的情况下也会发生。外源性花生四烯酸可增强胰岛对亚最大去极化浓度Kc1的胰岛素分泌反应，其最大有效浓度为30~40ĩ。这些观察结果表明，葡萄糖诱导的磷脂水解和胰岛内游离花生四烯酸的积累不是简单的与钙内流有关的附随现象，花生四烯酸积累可能在导致胰岛素分泌的信号过程中发挥作用。
Revised Manuscript Received April 5, 1991 abstract: Free fatty acids in isolated pancreatic islets have been quantified by gas chromatography-mass spectrometry after stimulation with insulin secretagogues. The fuel secretagogue D-glucose has been found to induce little change in islet palmitate levels but does induce the accumulation of sufficientunesterified arachidonate by mass to achieve an increment in cellular levels of 38-75 ĩ. Little of this free arachidonate is released into the perifusion medium, and most remains associated with the islets. Glucose-induced hydrolysis of arachidonate from islet cell phospholipids is reflected by release of the arachidonate metabolite prostaglandinE2 (PGE2) from perifused islets. Both the depolarizing insulin secretagogue tolbutamide (which is thought to act by inducing closure of 0-cell ATP-sensitive K+ channels and the influx of extracellular Ca2+ through voltage-dependent channels) and the calcium ionophore A23187 havealso been found to induce free ara-chidonate accumulation within and PGE2 release from islets. Surprisingly, a major fraction of glucose-induced eicosanoid release was found not to require Ca2+ influx and occurred even in Ca2+-free medium, in the presence of the Ca2+-chelating agent EGTA, and in the presence of the Ca2+ channel blockers verapamil and nifedipine. Exogenous arachidonic acid was found to amplify the insulin secretory response of perifused islets to submaximally depolarizing concentrations of KC1, and the maximally effective concentration of arachidonate was 30-40 ĩ. These observations suggest that glucose-induced phospholipid hydrolysis and free arachidonate accumulation in pancreatic islets are not simply epiphenomena associated with Ca2+ influx and that ara-chidonate accumulation may play a role in the signaling process which leads to insulin secretion.