Rorsman P, Renström E
The Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Headington, Oxford, UK.
Diabetologia. 2003 Aug;46(8):1029-45. doi: 10.1007/s00125-003-1153-1. Epub 2003 Jul 17.
Glucose-induced insulin secretion in response to a step increase in blood glucose concentrations follows a biphasic time course consisting of a rapid and transient first phase followed by a slowly developing and sustained second phase. Because Type 2 diabetes involves defects of insulin secretion, manifested as a loss of first phase and a reduction of second phase, it is important to understand the cellular mechanisms underlying biphasic insulin secretion. Insulin release involves the packaging of insulin in small (diameter approximately 0.3 micro m) secretory granules, the trafficking of these granules to the plasma membrane, the exocytotic fusion of the granules with the plasma membrane and eventually the retrieval of the secreted membranes by endocytosis. Until recently, studies on insulin secretion have been confined to the appearance of insulin in the extracellular space and the cellular events preceding exocytosis have been inaccessible to more detailed analysis. Evidence from a variety of secretory tissues, including pancreatic islet cells suggests, however, that the secretory granules can be functionally divided into distinct pools that are distinguished by their release competence and/or proximity to the plasma membrane. The introduction of fluorescent proteins that can be targeted to the secretory granules, in combination with the advent of new techniques that allow real-time imaging of granule trafficking in living cells (granule dynamics), has led to an explosion of our knowledge of the pre-exocytotic and post-exocytotic processes in the beta cell. Here we discuss these observations in relation to previous functional and ultra-structural data as well as the secretory defects of Type 2 diabetes.
血糖浓度逐步升高时，葡萄糖诱导的胰岛素分泌呈现双相时程，包括快速且短暂的第一相，随后是缓慢发展且持续的第二相。由于2型糖尿病存在胰岛素分泌缺陷，表现为第一相丧失和第二相减少，因此了解双相胰岛素分泌的细胞机制很重要。胰岛素释放涉及胰岛素包装在小（直径约0.3微米）分泌颗粒中，这些颗粒向质膜的运输，颗粒与质膜的胞吐融合，以及最终通过内吞作用回收分泌的膜。直到最近，对胰岛素分泌的研究一直局限于细胞外空间中胰岛素的出现，胞吐作用之前的细胞事件无法进行更详细的分析。然而，来自包括胰岛细胞在内的各种分泌组织的证据表明，分泌颗粒在功能上可分为不同的池，这些池通过其释放能力和/或与质膜的接近程度来区分。能够靶向分泌颗粒的荧光蛋白的引入，结合允许对活细胞中颗粒运输进行实时成像（颗粒动力学）的新技术的出现，使我们对β细胞胞吐前和胞吐后过程的了解激增。在这里，我们将这些观察结果与先前的功能和超微结构数据以及2型糖尿病的分泌缺陷联系起来进行讨论。
