Transient activation of calcium-dependent phospholipase A2 by insulin secretagogues in isolated pancreatic islets.
Transient activation of calcium-dependent phospholipase A2 by insulin secretagogues in isolated pancreatic islets.
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离体胰岛中胰岛素促分泌剂瞬时激活钙依赖性磷脂酶 A2。
DOI：
10.1021/bi00096a034
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发表时间：
1993
期刊：
影响因子：
2.9
通讯作者：
Wolf,BA
中科院分区：
文献类型：
--
作者：
Jolly,YC;Major,C;Wolf,BA
摘要：花生四烯酸被认为是胰岛0-细胞分泌胰岛素的重要和必需的介质，它可以调节细胞内Ca ~（2+）的稳态。胰岛素促分泌素，如葡萄糖和毒蕈碱激动剂卡巴胆碱，刺激花生四烯酸积累，尽管所涉及的机制是有争议的：卡巴胆碱被认为刺激磷脂酶A2，而葡萄糖诱导的花生四烯酸释放是二酰基甘油水解的结果[Konrad，R. J.，等人（1992）Biochem.J.287，283-290]。在胰岛素分泌克隆0-细胞RINmSF、HIT-T15和0-TC 3中，Ca 2+非依赖性磷脂酶A2主要是胞质的，而在胰岛中，它均匀地分布在粗膜部分和胞质之间。发现细胞膜相关的Ca 2+依赖性磷脂酶A2可被毫摩尔浓度的Ca 2+刺激，而细胞质Ca 2+依赖性活性可被微摩尔Ca 2+水平激活。为了确定磷脂酶A2是否在胰岛素分泌中被激活，我们评估了用促分泌素预处理完整胰岛是否影响磷脂酶A2活性，随后在膜或胞质组分中测量磷脂酶A2活性。葡萄糖和卡巴胆碱的组合瞬时激活钙依赖性（但不是钙依赖性）磷脂酶A2活性在10分钟，这对应于花生四烯酸释放的峰值。两种激动剂均未观察到作用。我们的研究结果表明，钙依赖性磷脂酶A2的激活可能是由于激动剂诱导的细胞内Ca 2+的增加。我们认为，胰岛钙依赖性磷脂酶A2的激活可能是重要的远端过程中的胰岛素分泌，如分泌颗粒胞吐。
Revised Manuscript Received September 3, 1993Ū abstract: Arachidonic acid is believedto be an important and necessary mediator of insulin secretion by 0-cells of islets of Langerhans, and it may regulate intracellular Ca2+ homeostasis. Insulin secretagogues, such as glucose and the muscarinic agonist carbachol, stimulate arachidonic acid accumulation, although the mechanisms involved are controversial: carbachol is believed to stimulate phospholipase A2, while glucose-induced arachidonic acid releaseis the result of diacylglycerol hydrolysis [Konrad, R. J., et al.(1992) Biochem. J. 287, 283-290], In insulin-secreting clonal 0-cells RINmSF, HIT-T15, and 0-TC3, Ca2+-independent phospholipase A2 was mainly cytosolic, while in islets it was equally distributed between a crude membrane fraction and the cytosol. A membrane-associated Ca2+-dependent phospholipase A2 was found to be stimulated by millimolar Ca2+ concentrations, while a cytosolic Ca2+-dependent activity was activated by micromolar Ca2+ levels. In order to determine whether phospholipase A2 was activated in insulin secretion, we assessed whether pretreatment of intact islets with secretagogues affected phospholipase A2 activity, which was subsequently measured in membrane or cytosolic fractions. The combination of glucose and carbacholtransiently activated Ca2+-dependent (but not Ca2+-independent) phospholipase A2 activity at 10 min, which corresponded to the peak of arachidonic acid release. No effect was seen with either agonistalone. Our results indicatethat activation of Ca2+-dependent phospholipase A2 may be due to agonist-induced increases in intracellular Ca2+. We suggest that activation of islet Ca2+-dependent phospholipase A2 may be important in a distal process of insulin secretion, such as secretory granule exocytosis.
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DOI：
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期刊：
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发表时间：
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