Vozzi C, Ullrich S, Charollais A, Philippe J, Orci L, Meda P
Department of Morphology, University of Geneva Medical School, Switzerland.
J Cell Biol. 1995 Dec;131(6 Pt 1):1561-72. doi: 10.1083/jcb.131.6.1561.
To assess whether connexin (Cx) expression contributes to insulin secretion, we have investigated normal and tumoral insulin-producing cells for connexins, gap junctions, and coupling. We have found that the glucose-sensitive cells of pancreatic islets and of a rat insulinoma are functionally coupled by gap junctions made of Cx43. In contrast, cells of several lines secreting insulin abnormally do not express Cx43, gap junctions, and coupling. After correction of these defects by stable transfection of Cx43 cDNA, cells expressing modest levels of Cx43 and coupling, as observed in native beta-cells, showed an expression of the insulin gene and an insulin content that were markedly elevated, compared with those observed in both wild-type (uncoupled) cells and in transfected cells overexpressing Cx43. These findings indicate that adequate levels of Cx-mediated coupling are required for proper insulin production and storage.
为了评估连接蛋白（Cx）的表达是否有助于胰岛素分泌，我们研究了正常和肿瘤性胰岛素产生细胞中的连接蛋白、间隙连接和细胞间偶联。我们发现，胰岛和大鼠胰岛素瘤的葡萄糖敏感细胞通过由Cx43构成的间隙连接在功能上偶联。相比之下，几条异常分泌胰岛素的细胞系的细胞不表达Cx43、间隙连接，也不存在细胞间偶联。在用Cx43 cDNA稳定转染纠正这些缺陷后，与野生型（未偶联）细胞和过表达Cx43的转染细胞相比，表达适度水平Cx43并发生偶联的细胞（如在天然β细胞中观察到的那样）显示胰岛素基因表达和胰岛素含量显著升高。这些发现表明，适当水平的Cx介导的细胞间偶联是胰岛素正常产生和储存所必需的。
