Halban P A, Powers S L, George K L, Bonner-Weir S
Diabetes. 1987 Jul;36(7):783-90. doi: 10.2337/diab.36.7.783.
Islets of Langerhans consist of four major endocrine cell types assembled in a highly organized manner critical for their function. The molecular forces governing islet cellular architecture are not understood. We determined whether adult rat islet cells carry information necessary for orderly assembly. Dispersed cells from adult rat islets were maintained in static suspension culture for 6 days. During this time the cells reassociated to form numerous aggregates. These aggregates were approximately half the size of native islets with a commensurate reduction in DNA and insulin content. However, both cellular composition and organization were remarkably similar to that of adult rat islets, in which the beta-cells form a central core surrounded by a discontinuous mantle of non-beta-cells. Thus, immunoperoxidase staining showed that in the aggregates, just as in intact islets cultured in parallel, 26% of the cells were non-beta-cells and of these, 94% were clearly peripheral. Non-beta-cells were similarly found to be peripheral, with beta-cells located centrally, even when the ratio of non-beta-cells to beta-cells had been altered. This was achieved by sorting the two cell populations by fluorescence-activated flow cytometry, resulting in aggregates with 79% non-beta-cells and 21% beta-cells. Insulin release from the aggregates was stimulated approximately ninefold by raising glucose from 50 to 300 mg/dl, which was comparable to that found for intact islets. The spontaneous formation of isletlike aggregates displaying appropriate cellular architecture indicates that the signals (molecules) needed for such organization are intrinsic to islet cells and are still expressed by them in adult life.
胰岛由四种主要的内分泌细胞类型组成，它们以高度有序的方式组装，这对其功能至关重要。目前尚不清楚控制胰岛细胞结构的分子作用力。我们确定成年大鼠胰岛细胞是否携带有序组装所需的信息。将成年大鼠胰岛分散的细胞在静态悬浮培养中维持6天。在此期间，细胞重新聚集形成许多聚集体。这些聚集体的大小约为天然胰岛的一半，DNA和胰岛素含量相应减少。然而，细胞组成和组织与成年大鼠胰岛非常相似，其中β细胞形成中央核心，周围是不连续的非β细胞包膜。因此，免疫过氧化物酶染色显示，在聚集体中，就像在平行培养的完整胰岛中一样，26%的细胞是非β细胞，其中94%明显位于外周。即使非β细胞与β细胞的比例发生了改变，也同样发现非β细胞位于外周，β细胞位于中央。这是通过荧光激活流式细胞术对两种细胞群体进行分选实现的，从而得到非β细胞占79%、β细胞占21%的聚集体。将葡萄糖浓度从50mg/dl提高到300mg/dl可刺激聚集体释放胰岛素约9倍，这与完整胰岛的情况相当。显示出适当细胞结构的胰岛样聚集体的自发形成表明，这种组织所需的信号（分子）是胰岛细胞固有的，并且在成年期仍由它们表达。
