PUTATIVE MEDIATORS OF INSULIN SECRETION

可能的胰岛素分泌介质包括钙、前列腺素和 环核苷酸。本课题研究的重点是确定合成物 后两种介质在大鼠胰腺分离胰岛中的分布 确定他们在胰岛素分泌过程中的参与程度。vbl.使用 分离的胰岛的匀浆，我们不仅在研究 主要的前列腺素，还有它们的新陈代谢。我们的生化途径 正在研究包括通过前列腺素代谢的花生四烯酸 环氧合酶、15-酮脱氢酶和还原酶。一部小说的证据 胰岛组织中的脂氧合酶途径也在研究中。此外，我们还 正在比较外分泌组织(腺泡)的前列腺素合成图谱 具有在胰岛中发现的轮廓的匀浆。前列腺素的合成 也将在完整的胰岛以及来自 打乱了小岛。各种胰岛素分泌物将被用来研究 胰岛前列腺素合成代谢在刺激过程中的反应 分泌和/或合成。 在前列腺素合成方面，磷脂酶A2(PLA2)活性 被认为决定了花生四烯酸对细胞的利用度 前列腺素合成。经曝晒的胰岛匀浆中PLA2活性为 正在评估，胰岛素分泌物对酶活性的影响是 被决定了。 我之前的研究表明，环鸟苷-3‘，5’-单磷酸 (GMP)可能在Inslin的第一阶段释放中起作用。一个更清晰的 高血压病患者胰岛素释放与循环GMP水平相关性的研究 分离的胰岛是寻找的，认为环核苷酸调节 钙交换现象，也许还有其他细胞生化活动。一个 大鼠骨骼肌磷脂酶A2活性与鸟苷环化酶活性的关系 完整的细胞一直是一个难以捉摸的问题，也许花生四烯酸的细胞水平 酸或前列腺素是重要因素。

Putative mediators of insulin secretion include calcium, prostaglandins, and cyclic nucleotides. The focus of my reseach is to determine the synthetic profiles of the latter two mediators in isolated islets from rat pancreas, and to determine their participation in the process in insulin secretion. Using homogenates of isolated islets, we are studing not only the synthesis of the primary prostaglandins, but also their metabolism. The biochemical pathways we are investigating include arachidonate metabolism through prostaglandin cyclooxygenase, 15-keto-dehydrogease, and reductase. Evidence for a novel liproxygenase pathways in islet tissue is also being studied. In addition we are comparing the prostaglandin synthesis profile of exocrine tissue (acinar) hemogenates with the profile found in islets. The synthesis of prostaglandins will also be studied in intact islet, as well as in isolated cells from disrupted islets. Various insulin secretogogues will be used to study the response of prostaglandin synthesis and metabolism in islets during stimulation of secretion and/or synthesis. With regard to prostaglandin synthesis, the activity of phospholipase A2 (PLA2) is believed to determine the availability of arachidonic acid for cell prostaglandin synthesis. The activity of PLA2 in insolated islet hemogenates is being assessed, and the effect of insulin secretogogues on enzyme activity is being determined. My previous research has suggested that cyclic guanosine-3',5'-monophosphate (GMP) may play a role in the first-phase release of inslin. A more clear understanding of the dependence of insulin release on cyclic GMP levels in the isolated islet is to be sought, with the view that cyclic nucleotides regulate calcium exchange phenomena and perhaps other cellular biochemical activities. A relationship between the activity of PLA2 and guanylate cyclase activity in intact cells has been an elusive problem, and perhaps cell levels of arachidonic acid or prostaglandins are important factors.