Misler Stanley, Zhou Zhuan, Dickey Adam S, Silva Amelia M, Pressel David M, Barnett David W
Departments of Medicine and Cell Biology, Washington University Medical Center, St. Louis, MO 63110, USA.
Channels (Austin). 2009 May-Jun;3(3):181-93. doi: 10.4161/chan.3.3.8972. Epub 2009 May 11.
Biphasic insulin secretion in response to glucose, consisting of a transient first phase followed by a progressive second phase, is well described in pancreatic islets. Using single canine beta-cells we have compared the time courses of electrical activity and insulin granule exocytosis to biphasic insulin secretion. Short trains of action potentials, similar those found during first phase insulin secretion, trigger phasic exocytosis from a small pool of insulin granules, likely an immediately releasable pool docked near voltage activated Ca(2+) channels. In contrast, plateau depolarizations to between -35 and -20 mV resembling those during second phase insulin secretion, trigger tonic exocytosis from a larger pool of insulin granules, likely a highly Ca(2+)-sensitive pool farther from Ca(2+) channels. Both phasic and tonic modes of exocytosis are enhanced by glucose, via its metabolism. Hence, in canine beta-cells two distinct components of exocytosis, tuned to two components of electrical activity, may contribute significantly to biphasic insulin secretion.
胰岛中对葡萄糖的双相胰岛素分泌,表现为短暂的第一相后接着进行性的第二相,已得到充分描述。我们使用单个犬β细胞,将电活动和胰岛素颗粒胞吐作用的时间进程与双相胰岛素分泌进行了比较。短串动作电位,类似于在第一相胰岛素分泌期间发现的那些,触发来自一小部分胰岛素颗粒的阶段性胞吐作用,这部分颗粒可能是靠近电压激活Ca(2+)通道停泊的一个立即释放池。相比之下,达到 -35至 -20 mV之间的平台期去极化,类似于第二相胰岛素分泌期间的情况,触发来自更大胰岛素颗粒池的持续性胞吐作用,这部分颗粒可能是离Ca(2+)通道更远的一个对Ca(2+)高度敏感的池。葡萄糖通过其代谢增强了阶段性和持续性胞吐作用模式。因此,在犬β细胞中,与电活动的两个成分相匹配的两种不同的胞吐作用成分,可能对双相胰岛素分泌有显著贡献。