Metz S A, Fujimoto W Y, Robertson R P
J Allergy Clin Immunol. 1984 Sep;74(3 Pt 2):391-402. doi: 10.1016/0091-6749(84)90137-4.
Although an association between membrane phospholipid turnover and exocytotic hormone release has long been recognized, a causal relationship has not been firmly established. Recent studies suggest that glucose (and probably other insulin secretagogues) activates phospholipases and thereby releases membrane-bound arachidonic acid (AA). AA is then converted through islet 12-lipoxygenase to mediators or modulators of insulin release (tentatively identified as peroxides and epoxides of arachidonate). These products may be critical links in stimulus-secretion coupling, since blockade of either AA release or lipoxygenation abrogates insulin release induced by glucose and many other (but not all) stimuli. Cogeneration of prostaglandins from AA through the cyclooxygenase pathway may directly or indirectly modulate the formation and/or effect of lipoxygenase products. A critical role for lipoxygenase products (and possibly metabolites of AA synthesized by other pathways, such as P-450-dependent monooxygenases) may extend to many secretory cells in addition to pancreatic beta cells. The phasic release of AA described in many cells could explain the biphasic pattern of insulin release induced by glucose. Since some phospholipases and lipoxygenases are Ca++ activated, the release of AA in conjunction with its oxygenation appears to be a concerted system generating "third messengers" for hormone release.
尽管膜磷脂周转与胞吐性激素释放之间的关联早已为人所知，但因果关系尚未得到确凿证实。最近的研究表明，葡萄糖（可能还有其他胰岛素促分泌剂）激活磷脂酶，从而释放膜结合的花生四烯酸（AA）。然后，AA通过胰岛12 - 脂氧合酶转化为胰岛素释放的介质或调节剂（初步鉴定为花生四烯酸的过氧化物和环氧化物）。这些产物可能是刺激 - 分泌偶联中的关键环节，因为阻断AA释放或脂氧合作用会消除由葡萄糖和许多其他（但不是所有）刺激诱导的胰岛素释放。通过环氧化酶途径从AA生成前列腺素可能直接或间接调节脂氧合酶产物的形成和/或作用。脂氧合酶产物（以及可能由其他途径合成的AA代谢产物，如P - 450依赖性单加氧酶）的关键作用可能不仅限于胰腺β细胞，还扩展到许多分泌细胞。许多细胞中描述的AA的阶段性释放可以解释葡萄糖诱导的胰岛素释放的双相模式。由于一些磷脂酶和脂氧合酶是由Ca++激活的，AA的释放及其氧化作用似乎是一个协同系统，为激素释放产生“第三信使”。
