Meda P, Michaels R L, Halban P A, Orci L, Sheridan J D
Diabetes. 1983 Sep;32(9):858-68. doi: 10.2337/diab.32.9.858.
The extent of gap junctions and dye coupling between insulin-producing B-cells was analyzed on islets of Langerhans isolated from adult rats treated for one day with glibenclamide, an insulin secretagogue, or diazoxide, a blocker of insulin release, or a combination of the two drugs. Glibenclamide treatment was associated with a marked depletion of the islet insulin content, an effect which was blocked by pretreatment of the rats with diazoxide. Diazoxide alone caused a marked increase in the plasma glucose level, and a decrease in the level of circulating insulin and in the hormone content of the B-cells. Quantitative analysis showed that (1) under control conditions, B-cells are connected by minute gap junctions (as evaluated on freeze-fracture replicas) and show a nonuniform and apparently restricted dye coupling (as determined by microinjection of the low-molecular-weight fluorescent probe Lucifer Yellow CH); (2) each of the three treatments tested significantly increased the relative and absolute gap junction area of the B-cells and the number of detectable, dye coupled B-cells per microinjection. After treatment with glibenclamide alone or with diazoxide plus glibenclamide, a 1.5-1.8-fold increase in gap junction area and a 2.7-3.7-fold increase in the number of dye-coupled B-cells were observed. In contrast, following treatment with diazoxide alone, gap junctions and dye coupling were found increased 1.8 and 8.7 times, respectively, as compared with control values.
对从成年大鼠分离的胰岛进行分析，这些大鼠用胰岛素促分泌剂格列本脲、胰岛素释放阻滞剂二氮嗪或这两种药物的组合处理一天，研究胰岛素分泌B细胞之间缝隙连接和染料偶联的程度。格列本脲处理与胰岛胰岛素含量显著减少有关，二氮嗪预处理大鼠可阻断这种作用。单独使用二氮嗪会导致血浆葡萄糖水平显著升高，循环胰岛素水平和B细胞激素含量降低。定量分析表明：（1）在对照条件下，B细胞通过微小缝隙连接相连（通过冷冻断裂复制品评估），并表现出不均匀且明显受限的染料偶联（通过低分子量荧光探针鲁米诺黄CH显微注射确定）；（2）所测试的三种处理中的每一种都显著增加了B细胞的相对和绝对缝隙连接面积以及每次显微注射中可检测到的染料偶联B细胞的数量。单独用格列本脲或二氮嗪加格列本脲处理后，缝隙连接面积增加1.5 - 1.8倍，染料偶联B细胞数量增加2.7 - 3.7倍。相比之下，单独用二氮嗪处理后，缝隙连接和染料偶联分别比对照值增加了1.8倍和8.7倍。
