STRUCTURE-FUNCTION-RELATIONSHIPS IN PANCREATIC-ISLETS - SUPPORT FOR INTRAISLET MODULATION OF INSULIN-SECRETION
STRUCTURE-FUNCTION-RELATIONSHIPS IN PANCREATIC-ISLETS - SUPPORT FOR INTRAISLET MODULATION OF INSULIN-SECRETION
复制标题
DOI：
10.1210/endo-117-5-2073
复制
发表时间：
1985-01-01
期刊：
影响因子：
4.8
通讯作者：
SCOTT, RS
中科院分区：
文献类型：
--
作者：
HOPCROFT, DW;MASON, DR;SCOTT, RS
使用三种结构不同的胰岛组织制剂在体外研究胰岛 B 细胞功能：分离的完整胰岛、单独附着于微载体珠的分散的胰岛细胞和重新聚集的胰岛细胞。单细胞制剂消除了细胞间通讯机制，而在聚集体中，细胞间通讯被重新建立，并恢复了定义的微环境。灌注研究测量了三个胰岛组织的非刺激和葡萄糖和精氨酸刺激的胰岛素释放。胰岛素分泌率表示为细胞 DNA 含量的函数，允许在组织之间进行直接比较。在低浓度（2.8 或 5.5 mM）葡萄糖灌注期间，单个胰岛细胞的分泌率比完整胰岛细胞的分泌率高出 6 倍（P < 0.001）。用 2.8 mM 葡萄糖和 100 或 500 pg 胰高血糖素/ml 灌注胰岛细胞没有效果，而 GH 释放抑制因子（300 和 1000 pg/ml）使非刺激胰岛素分泌率降低 15%（P < 0.05）。重新聚集后，基础胰岛素分泌率恢复到完整胰岛的水平。葡萄糖 (5.5-30 mM) 和 L-精氨酸 (5-20 mM) 引发单个胰岛细胞的第一阶段胰岛素反应，与完整细胞观察到的结果没有显着差异；相比之下，单个胰岛对葡萄糖的第二相反应约为完整胰岛的 50%，并且不存在对精氨酸的第二相反应。在外源胰高血糖素存在下，单胰岛细胞对 5.5 mM 葡萄糖的第一相和第二相胰岛素反应分别增强 2.2 倍（P < 0.01）和 2.8 倍（P < 0.05），从而产生完整胰岛的分泌特征。单个胰岛的重新聚集与对葡萄糖和精氨酸刺激的第一和第二阶段胰岛素反应显着增加相关。这些数据表明，胰岛微观解剖结构的破坏会导致胰岛素分泌反应的改变，并且所观察到的影响可以部分通过外源胰高血糖素和 GH 释放抑制因子以及通过重新聚集来逆转。尽管不同的机制对于非刺激的第一相和第二相胰岛素释放似乎很重要，但这些发现支持直接细胞间通讯和胰岛 A 和 D 细胞的激素分泌在调节 B 细胞功能中的作用。
Pancreatic islet B cell function was studied in vitro using three structurally different preparations of islet tissues: isolated, intact islets, dispersed islet cells attached singly to microcarrier beads, and reaggregated islet cells. Mechanisms of intercellular communication are eliminated with single cell preparations, whereas in aggregates cell to cell communications are reestablished and a defined microenvironment restored. Perifusion studies measured nonstimulated and glucose- and arginine-stimulated insulin release from the three islet tissues. Insulin secretion rates were expressed as a function of cellular DNA content, permitting direct comparison between tissues. During perifusion with low (2.8 or 5.5 mM) glucose concentrations, secretion rates of single islet cells were up to 6-fold greater (P < 0.001) than those of intact islets. Perifusion of islet cells with 2.8 mM glucose and 100 or 500 pg glucagon/ml had no effect whereas GH-release-inhibiting factor (300 and 1000 pg/ml) decreased nonstimulated insulin secretion rates by 15% (P < 0.05). After reaggregation, basal insulin secretion rates were restored toward those of intact islets. Glucose (5.5-30 mM) and L-arginine (5-20 mM) elicited first phase insulin responses from single islet cells that were not significantly different from those observed with intact cells; in contrast, second phase responses of single islets to glucose were approximately 50% those seen with intact islets, and their second phase responses to arginine were absent. Single islet cell first and second phase insulin responses to 5.5 mM glucose were enhanced 2.2-fold (P < 0.01) and 2.8-fold (P < 0.05), respectively, in the presence of exogenous glucagon, resulting in secretory profiles characteristic of intact islets. Reaggregation of single islet was associated with markedly increased first and second phase insulin responses to both glucose and arginine stimulation. These data show that disruption of the islet microanatomy results in alteration of insulin secretory responses and that seen effects can be reversed, in part by exogenous glucagon and GH-release-inhibiting factor, and by reaggregation. Although different mechanisms appear important for nonstimulated, first and second phase insulin release, the findings support a role for both direct intercellular communication and hormonal secretion by islet A and D cells in the modulation of B cell function.